Thyroid, Ahead of Print.
http://bit.ly/2DSC8JM
Δευτέρα 4 Φεβρουαρίου 2019
A Practical Approach for the Verification and Determination of Site- and Trimester-Specific Reference Intervals for Thyroid Function Tests in Pregnancy
Cochlear implantation as a treatment for single-sided deafness and asymmetric hearing loss: a randomized controlled evaluation of cost-utility
Abstract
Background
Single-sided deafness (SSD) and asymmetric hearing loss (AHL) have recently been proposed as a new indication for cochlear implantation. There is still no recommended treatment for these hearing deficits, and most options considered rely on the transfer of sound from the poor ear to the better ear, using Contralateral Routing of the Signal (CROS) hearing aids or bone conduction (BC) devices. In contrast, cochlear implantation allows the poor ear to be stimulated and binaural hearing abilities to be partially restored. Indeed, most recently published studies have reported an improvement in the spatial localisation of an incoming sound and better speech recognition in noisy environments after cochlear implantation in SSD/AHL subjects. It also provides consistent relief of tinnitus when associated. These encouraging hearing outcomes raise the question of the cost-utility of this expensive treatment in an extended indication.
Methods
The final endpoint of this national multicentre study is to determine the incremental cost-utility ratio (ICUR) of cochlear implantation in comparison to the current standard of care in France through simple observation, using a randomised controlled trial. Firstly, the study comprises a prospective and descriptive part, where 150 SSD/AHL subjects try CROS hearing aids and a BC device for three weeks each. Secondly, the choice is made between CROS hearing aids, BC implanted device and cochlear implantation. Hearing outcomes and quality of life measurements are described after 6 months for the subjects who chose CROS, BC or declined any option. The subjects who opt for cochlear implantation are randomised between one group where the cochlear implant is inserted without delay and one group of simple initial observation. Hearing outcomes and quality of life measurements are compared after 6 months.
Discussion
The present study was designed to assess the efficiency of cochlear implantation in SSD/AHL. A favourable cost-utility ratio in this extended indication would strengthen the promising clinical results and justify a reimbursement by the health insurance. The efficiency of other options (CROS, BC) will also be described.
Trial registration
This research has been registered in ClinicalTrials.gov (http://www.clinicaltrials.gov/), the 29th July 2014 under the n°NCT02204618.
http://bit.ly/2UGSSsW
Effectiveness of simultaneous foliar application of Zn and Mn or P to reduce Cd concentration in rice grains: a field study
Abstract
Excess cadmium (Cd) in agricultural soils can be taken up by rice plants and concentrated in the grain, presenting a human health risk. In this study, we field tested the effects of three foliar treatments (zinc (Zn) alone, or combined with manganese (ZnMn) or phosphorus (ZnP)) on the Cd concentration and grain yield of six rice cultivars (C Liangyou 7, Fengyuanyou 272, Xiangwanxian 12, Tianyouhuazhan, Xiangwanxian 13, and Jinyou 284) at the grain filling stage. Our results showed that rice yield and Cd, Zn, Mn, P, and K concentrations were significantly different among the cultivars (p < 0.05); for example, Jinyou 284 recorded lower Cd levels than any other cultivar. Application of Zn, ZnMn, and ZnP had no significant effect on rice yield and Mn, P, and K concentrations for all cultivars. Compared with the control, Cd concentrations after treatment with Zn, ZnMn, and ZnP decreased by 19.03–32.55%, 36.63–55.78% (p < 0.05), and 25.72–49.10%, respectively, while Zn concentrations increased by 11.02–29.38%, 10.63–32.67%, and 11.97–36.82%, respectively. There was a significant negative correlation between Cd and Zn concentrations (p < 0.01). All three treatments increased Zn and reduced Cd concentration in rice grains, though ZnMn was most effective. Therefore, cultivar selection and Zn fertilizer application are effective strategies to minimize Cd concentration in rice grains. However, the lowest result still exceeded the Chinese Cd safety limit (0.2 mg Cd kg−1) by a factor of 2.6, demonstrating that additional effective measures should be simultaneously used to further reduce the accumulation of Cd in rice grains.
http://bit.ly/2SvYtVy
An update on clinical safety of adalimumab in treating psoriasis: A systematic review and meta‐analysis based on 20 randomized controlled trials
Summary
Purpose
The current meta‐analysis was conducted to better evaluate the role of adalimumab for patients with psoriasis in terms of its safety profile on the basis of eligible randomized controlled trials (RCTs).
Methods
The following electronic databases such as Cochrane, PubMed, and Embase database involving the index words were screened and identified for qualified studies updated to December 2018. Associated publications and sources were hand‐searched for more related details. To further analyze the main outcomes, the odds ratio (OR) and mean difference (MD) with its 95% confidence interval (95% CI) were utilized.
Results
There were a total of 20 RCTs involving respective 3795 and 3266 patients in the adalimumab and control group that met our inclusion criteria. According to the aggregated results, the adalimumab group was highly associated with significant improvement in the incidence of adverse event (AE), infection, and injection site reaction on comparison of the control group. Nevertheless, no remarkable differences were found between the two study groups in terms of the incidence of serious AE, serious infection as well as the discontinuation of study drug caused by AE.
Conclusion
Adalimumab was proved to be linked to higher incidence of AE, infection, and injection site reaction during the therapy process of psoriasis based on high‐quality RCTs. In addition, there was no association between adalimumab therapy and serious AE, serious infection and the discontinuation of study drug caused by AE in patients harboring psoriasis according to eligible RCTs.
http://bit.ly/2RF7oQ3
An update on clinical safety of adalimumab in treating psoriasis: A systematic review and meta‐analysis based on 20 randomized controlled trials
Summary
Purpose
The current meta‐analysis was conducted to better evaluate the role of adalimumab for patients with psoriasis in terms of its safety profile on the basis of eligible randomized controlled trials (RCTs).
Methods
The following electronic databases such as Cochrane, PubMed, and Embase database involving the index words were screened and identified for qualified studies updated to December 2018. Associated publications and sources were hand‐searched for more related details. To further analyze the main outcomes, the odds ratio (OR) and mean difference (MD) with its 95% confidence interval (95% CI) were utilized.
Results
There were a total of 20 RCTs involving respective 3795 and 3266 patients in the adalimumab and control group that met our inclusion criteria. According to the aggregated results, the adalimumab group was highly associated with significant improvement in the incidence of adverse event (AE), infection, and injection site reaction on comparison of the control group. Nevertheless, no remarkable differences were found between the two study groups in terms of the incidence of serious AE, serious infection as well as the discontinuation of study drug caused by AE.
Conclusion
Adalimumab was proved to be linked to higher incidence of AE, infection, and injection site reaction during the therapy process of psoriasis based on high‐quality RCTs. In addition, there was no association between adalimumab therapy and serious AE, serious infection and the discontinuation of study drug caused by AE in patients harboring psoriasis according to eligible RCTs.
http://bit.ly/2RF7oQ3
Capecitabine-induced bilateral ectropion: A rare ocular manifestation requiring surgical intervention
Journal of Cutaneous and Aesthetic Surgery 2018 11(4):241-244
It has been established that many chemotherapeutic agents are associated with a variety of ocular side effects. As an antineoplastic agent, 5-fluorouracil (5-FU) is the chemotherapeutic agent that is frequently linked with cicatricial ectropion. Capecitabine is a prodrug of 5-FU and has a more favorable side effect profile than 5-FU. Frequent side effects of capecitabine include gastrointestinal events and hand–foot–mouth syndrome; cicatricial ectropion is rather uncommon. Enzyme deficiencies affecting the capecitabine metabolism have been reported to be associated with exaggerated generalized systemic and cutaneous side effects; however, there are no cases in the literature reporting capecitabine-induced isolated bilateral-progressive ectropion. Although cessation of the agent is frequently sufficient for the treatment of ectropion, close follow-up is indicated in such patients as permanent damage may occur if the problem is left untreated. We report a case of capecitabine-induced bilateral cicatricial ectropion refractory to treatment cessation, ultimately requiring surgical treatment.
http://bit.ly/2Twf60R
Injection lipolysis: A systematic review of literature and our experience with a combination of phosphatidylcholine and deoxycholate over a period of 14 years in 1269 patients of Indian and South East Asian origin
Journal of Cutaneous and Aesthetic Surgery 2018 11(4):222-228
Background: Phosphatidylcholine and deoxycholate (PC–DC) injections have been used as nonsurgical alternatives to liposuction. DC as a constituent for lipolysis has recently been approved by the US Food and Drug Administration. Aim: PC and DC have independently been used in lipolysis. We hereby present a systematic review of literature on injection lipolysis and share our experience of using DC in combination with PC for injection lipolysis. We have retrospectively evaluated the effects of PC–DC treatments in varied age groups, both sexes, and over different target areas. Materials and Methods: This study spans over 14 years wherein 1269 patients of different age groups and sex were treated with injection lipolysis with PC–DC combination. The PC–DC cocktail injection was given to all patients for an average four sessions every 4 weeks, and the results were assessed after 8 weeks from the last session. Results: The effects were best appreciated over the face (malar, jawline, and submental areas) and upper arm, whereas average effect was observed on the thighs and around the knees. We have also used lipolysis as a primary modality as well as a touch-up modality following liposuction. The results are better appreciated in primary lipolysis. The need for follow-up sessions (1–2 sessions) of lipolysis and the quantification of results in subsequent sessions reveal that maximal improvement is achieved in the first session. Conclusion: PC–DC cocktail used for lipolysis as a local administration is effective for reducing unwanted fat. It shows great efficacy in treating localized fat, especially over the face and bra roll in the women of younger age group (20–30 years).
http://bit.ly/2BiKIje
Overview of medical therapies and phototherapy in vitiligo based on their pathogenetic action and the role of platelet-rich plasma
Journal of Cutaneous and Aesthetic Surgery 2018 11(4):167-168
http://bit.ly/2TAHYFm
Learning from the past, gleaning into future
Journal of Cutaneous and Aesthetic Surgery 2018 11(4):165-166
http://bit.ly/2BiKDvW
Logic of hair transplantation
Journal of Cutaneous and Aesthetic Surgery 2018 11(4):169-172
Hair transplant is a seemingly illogical process wherein we are using a small number of hairs to cover a large area of baldness. This is possible if one understands the logic of this equation. Understanding the pattern of hair distribution, and the sequence of balding, helps us learn the limitations of this technique and give the best possible results to the patient. In this article, we aim to give an understanding of all the processes associated with hair transplantation and the logic behind the same.
http://bit.ly/2Ty4oGX
Is prophylactic immunosuppressive therapy for patients with a history of postsurgical pyoderma gangrenosum necessary?
Journal of Cutaneous and Aesthetic Surgery 2018 11(4):234-236
Postsurgical pyoderma gangrenosum (PSPG) is a rare but serious surgical complication with a predilection for the breast and abdomen. Immunosuppression is the mainstay of treatment of PSPG. In addition, it has become a common practice for clinicians to prophylactically treat patients with a history of PSPG with corticosteroids or immunomodulators during subsequent operative procedures to prevent recurrence. Although many practitioners have reported successful outcomes with these measures, currently no protocol exists for prophylactic perioperative therapy. Here, we present the clinical course and 10-year follow-up of a woman who developed PSPG after undergoing body-contouring surgery, subsequently underwent multiple operative procedures without prophylactic immunosuppression, and has not experienced recurrence of PSPG. This case suggests that prophylactic therapy may not be necessary in all patients with a history of PSPG and shows that further research into the use of perioperative immunosuppression to prevent PSPG recurrence may be warranted.
http://bit.ly/2BlB8Mz
Controversies in hair transplantation
Journal of Cutaneous and Aesthetic Surgery 2018 11(4):173-181
Hair transplantation being a relatively new field, several aspects raise issues and controversies. The issues refer to both ethics and evidence and how practitioners and the community need to deal with them. This article deals with few of such diverse issues as follicular unit transplantation versus follicular unit excision, safe donor area, platelet-rich plasma, and minimum qualification for performing hair transplantation.
http://bit.ly/2TvWIoT
“Jigsaw puzzle” advancement flap
Journal of Cutaneous and Aesthetic Surgery 2018 11(4):248-249
http://bit.ly/2BiKdFY
Complications in hair transplantation
Journal of Cutaneous and Aesthetic Surgery 2018 11(4):182-189
Hair transplantation is a relatively safe surgery and is associated with very few complications. It is a cosmetic surgery so the complications may impact social and psychological aspect of the patient. Every hair transplantation surgeon should be aware of possible complications and techniques for the prevention and techniques of their management. Most of the complications are avoidable and can be minimized by proper surgical technique and wound care. Counseling and discussion with the patient before surgery help in proper planning and avoid patient dissatisfaction. Every patient should be individualized, planned, and operated with an aim to zero-down the complications and complaints.
http://bit.ly/2Tx9cfU
Fractional carbon dioxide laser in combination with topical corticosteroid application in resistant alopecia areata: A case series
Journal of Cutaneous and Aesthetic Surgery 2018 11(4):217-221
Introduction: Intradermal steroid injections are used as treatment option in resistant alopecia areata. However, it is difficult and quite painful to treat large areas of alopecia with this modality. Objective: To assess the efficacy and safety profile of a combination of fractional carbon dioxide (CO2) treatment followed by topical corticosteroid application in resistant alopecia areata. Materials and Methods: Ten cases of resistant alopecia areata who had not responded to multiple treatment modalities were treated with fractional CO2 laser followed by topical application of triamcinolone spray (10mg/mL) on the resistant lesions. Patients received 4–8 sessions that were repeated at an interval of 3–4 weeks. Response to treatment was assessed on a quartile physician assessment scale and labeled as excellent (>75% regrowth), good (50%–75% regrowth), fair (26%–50% response), and poor (<25% regrowth). Results: Eight of these ten cases completed the treatment process. Seven of these eight patients had complete recovery of the area treated. One patient however did not show good response even after four sessions. No significant adverse effects were noted in any of the patients. Conclusion: Fractional CO2 laser in combination with topical triamcinolone can prove to be an effective treatment option in resistant alopecia areata.
http://bit.ly/2Bl0x9r
Donor harvesting: Strip dissection
Journal of Cutaneous and Aesthetic Surgery 2018 11(4):190-194
Hair transplant is a constantly evolving science. From the time that it was conceived by Dr. Norman Orentreich to the present state, the procedure of hair transplant has undergone multiple advancements. In this article, we discuss in brief regarding the strip follicular unit transplantation. We summarize the major points regarding the procedure of strip follicular unit transplantation along with some nuggets of experience that we have gathered over time. We briefly deal with the indications, anesthesia, procedure, and complications of strip follicular unit transplantation and some special scenarios like the repeat excision of strip.
http://bit.ly/2TyPuAo
Deoxycholate (ATX-101) mixed with lidocaine to minimize pain/discomfort in nonsurgical treatment of submental fullness appearance
Journal of Cutaneous and Aesthetic Surgery 2018 11(4):229-233
In the present study pain/discomfort reduction in submental fullness treatment with the injections of a DC based drug (ATX-101, Allergan, Dublin, Ireland) premixed with lidocaine 2% on a sample of 12 patients retrospectively evaluated has been performed All patients indicated improvement in skin tightening from the 2nd month postinjection. Three patients had minor ecchymoses at the injection sites, which resolved spontaneously within 10 days posttreatment. One patient experienced dysesthesia of the treated area, which lasted approximately 40 days and resolved spontaneously. No other complications—such as nerve paresis or alopecia—were recorded. No patient required analgesic drugs postinjection.
http://bit.ly/2BiK1Xa
Donor harvesting: Follicular unit excision
Journal of Cutaneous and Aesthetic Surgery 2018 11(4):195-201
FUE or follicular unit excision is one of the methods for hair follicle harvesting in hair transplantation. FUE involves harvesting hairs from the donor area, under local anesthesia which is most commonly the scalp but occasionally beard, chest and other parts of the body, using a circular punch less than a mm, mounted on a manual handle or a motorized hand device or more recently a robotic device.First hair transplant was done by Dr Shoji Okuda in 1937. The term "follicular unit extraction" was coined by William Rassman in 2002. The modern era of FUE begins with the work of several surgeons Woods, Rassman, Cole, Harris and Rose. FUE has gone through various stages of development from manual to motorized and blunt to sharp, serrated trumpet and flared punches. Now the use of the robot in FUE with extraction and incision making is also in use.In 2017 nomenclature committee headed by Parsa Mohebi of ISHRS, recommended the term "FOLLICULAR UNIT EXCISION" is most appropriate as it explains the two steps of the process: incision and extraction and incision is done by a physician. FUE is a surgeon based time-consuming procedure with the long learning curve. Use of motorized device and sharp punches has certainly helped to increase speed in an experienced hand. FUE method of hair transplant is the most demanding procedure. If done properly it is a safe procedure. with the experience, use of better quality of instrument the disadvantages of FUE like transection can be reduced. The above informations were collected from various papers published in authentic journals and textbooks.
http://bit.ly/2Ty7ET0
Impacted foreign bodies in the maxillofacial region–A series of three cases
Journal of Cutaneous and Aesthetic Surgery 2018 11(4):237-240
Penetrating injuries to the maxillofacial region are very common. Foreign bodies embedded deep in the maxillofacial region due to these injuries pose a challenge to an oral and maxillofacial surgeon. These objects may become a potent source of pain and infection. Early diagnosis of these foreign bodies can be achieved by the use of plain radiographs, ultrasonography, computed tomographic scans, and magnetic resonance imaging. Once diagnosed and located, these foreign bodies should be removed. Here, we report three such cases where early diagnosis of these foreign bodies embedded in the maxillofacial region lead to their early and successful removal without complications.
http://bit.ly/2BiKhp6
Recipient area
Journal of Cutaneous and Aesthetic Surgery 2018 11(4):202-210
Recipient area is the canvas in a hair transplant surgery, where the surgeon can truly display his artistic creativity and deliver an aesthetic masterpiece, after all hair transplantation is as much about art as science. There are four main steps in dealing with the recipient area. Marking the hairline and estimation of grafts is the most important steps to give a natural look. There are multiple anatomical markers that need to be addressed while drawing a hairline. The second step is the anesthesia and it should be as painless as possible. This is followed by implantation, which can be achieved by various techniques. There are multiple technicalities to be considered while implanting, such as density, angle, and direction. Once implantation is done, the final step is appropriate postoperative care. Each of these steps has been discussed in detail in this chapter.
http://bit.ly/2TAHXBi
Asymptomatic pinkish-red nodule over the posterolateral tongue
Journal of Cutaneous and Aesthetic Surgery 2018 11(4):245-247
A young otherwise healthy male presented with asymptomatic pinkish-red nodule over postero-lateral tongue with the suspicion of having developed oral cancer. Biopsy from the lesion showed multiple circumscribed nodules in the lamina propria comprised of numerous oval and spindle-shaped cells. Abundant lymphatic tissue with germinal centres were also observed. Differentials included mucosal neuroma, traumatic neuroma, subgemmal neurogenous plaque, neurofibroma, and lingual tonsils. This quiz discusses the diagnosis and approach to the differential diagnoses in such a clinical setting.
http://bit.ly/2BkxOBw
A randomized controlled, single-observer blinded study to determine the efficacy of topical minoxidil plus microneedling versus topical minoxidil alone in the treatment of androgenetic alopecia
Journal of Cutaneous and Aesthetic Surgery 2018 11(4):211-216
Background: Androgenetic alopecia (AGA) is the most common form of hair loss in adults, which is generally progressive in the absence of treatment. As a head full of healthy hair adds to the cosmetic appeal of the individual, the consequences of AGA are predominantly psychological. Currently, topical minoxidil is the first-line treatment for AGA. Many adjuvant treatment modalities have been used synergistically with minoxidil. Microneedling is one among such adjuvant treatments, which works by various mechanisms to stimulate the dermal papillary cells that play a key role in hair growth. Aim: To compare the efficacy of microneedling along with topical minoxidil and topical minoxidil alone in the treatment of AGA in men. Materials and Methods: Sixty-eight men with Norwood–Hamilton grade III and IV AGA were recruited for the study. After randomization, one group was treated with weekly microneedling and twice daily application of 5% minoxidil solution and the other group was treated with twice daily application of 5% minoxidil solution alone. Global photographs were taken at baseline (pretreatment) and at end of the study duration. Trichoscopic images were taken from a targeted fixed area before treatment (baseline) and at end of the therapy from where hair count was also carried out. The two primary efficacy parameters were assessed: increase in the hair count from that of the baseline and patient self-assessment of hair growth at the end of the study. Results: The mean increase in hair count in the targeted area of one square inch at the end of the treatment was significantly greater for the combination treatment group (12.52/inch2) compared to that for the minoxidil alone group (1.89/inch2). Four patients in the "microneedling plus topical minoxidil" group reported a 50% improvement versus none in the "minoxidil alone" group. Conclusion: Our study showed that the combination of microneedling and topical minoxidil treatment was superior compared to topical minoxidil alone with regard to increase in the hair count and patient satisfaction, although the response achieved was not cosmetically significant.
http://bit.ly/2TwIMLk
Chemical peeling for nail disorders: Author response to the published comment
Journal of Cutaneous and Aesthetic Surgery 2018 11(4):250-251
http://bit.ly/2DS9s3M
Cochlear implantation as a treatment for single-sided deafness and asymmetric hearing loss: a randomized controlled evaluation of cost-utility
Single-sided deafness (SSD) and asymmetric hearing loss (AHL) have recently been proposed as a new indication for cochlear implantation. There is still no recommended treatment for these hearing deficits, and ...
http://bit.ly/2UHSWZt
Patient-Reported Satisfaction and Quality of Life in Postmastectomy Radiated Patients: A Comparison between Delayed and Delayed Immediate Autologous Breast Reconstruction in a Predominantly Minority Patient Population
J reconstr Microsurg
DOI: 10.1055/s-0039-1677798
Background Delayed immediate (DI) autologous breast reconstruction consists of immediate postmastectomy tissue expander placement, radiation therapy, and subsequent autologous reconstruction. The decision between timing of reconstructive methods is challenging and remains to be elucidated. We aim to compare patient reported outcomes and quality of life between delayed and DI reconstruction. Methods A retrospective review of all patients, who underwent autologous breast reconstruction at Montefiore Medical Center from January 2009 to December 2016, was conducted. Patients who underwent postmastectomy radiotherapy were divided into two cohorts: delayed and DI autologous breast reconstruction. Patients were mailed a BREAST-Q survey and their responses, demographic information, complications, and need for revisionary procedures were analyzed. Results A total of 79 patients met inclusion criteria: 34.2% (n = 27) in the delayed and 65.8% (n = 52) in the DI group. 77.2% (n = 61) of patients were a minority population. Patients in each cohort had similar baseline characteristics; however, the DI cohort was more likely to have bilateral reconstruction (46.2% [n = 24] vs. 7.4% [n = 2]; p = 0.0005) and to have major mastectomy flap necrosis (22.4% [n = 17] vs. 0.0% [n = 0]; p = 0.002). Premature tissue expander removal occurred in 17.3% (n = 9) of patients in the DI group. BREAST-Q response rates were 44.4% (n = 12) in the delayed group and 57.7% (n = 30) in the DI group. Responses showed similar satisfaction with their breasts, well-being, and overall outcome. Conclusions Delayed and DI autologous breast reconstruction yield similar patient-reported satisfaction; however, patients undergoing DI reconstruction have higher rates of major mastectomy necrosis. Furthermore, patients in the DI group risk premature tissue expander removal.
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Article in Thieme eJournals:
Table of contents | Abstract | Full text
http://bit.ly/2SfpLk4
Estimating CDKN2A mutation carrier probability among global familial melanoma cases using GenoMELPREDICT
Although rare in the general population, highly penetrant germline mutations in CDKN2A are responsible for 5-40% of melanoma cases reported in melanoma-prone families. We sought to determine whether MELPREDICT was generalizable to a global series of melanoma families and whether performance improvements can be achieved.
http://bit.ly/2RG7O8S
Pigments in American Tattoo Inks and their Propensity to Elicit Allergic Contact Dermatitis
Tattoos have become increasingly common in the United States. Historically, tattoo inks were comprised of metallic pigments which had the potential to cause allergic contact dermatitis. Data have been lacking on the current use of these pigments in tattoo ink.
http://bit.ly/2S9ko5D
Early Detection of Acral Melanoma: A Review of Clinical, Dermoscopic, Histopathologic, and Molecular Characteristics
Acral lentiginous melanoma is a distinct subtype of melanoma on acral skin. Patient presentation at later stages as well as delayed diagnosis by physicians contribute to a worse associated prognosis and survival rate. Despite our progress on understanding the key features of this disease, the diagnosis of early stage acral melanoma is still challenging. It is essential to integrate clinical, dermoscopic, and histological findings in the diagnosis of acral lentiginous melanoma. In addition, molecular studies can be helpful.
http://bit.ly/2RApLpz
Coffee, tea, caffeine, and risk of non-melanoma skin cancer in a Chinese population: The Singapore Chinese Health Study
1.Although studies in Caucasians suggest that caffeine may reduce the risk of non-melanoma skin cancer (NMSC), studies among darker-skinned populations are lacking. 2.We showed that intake of coffee or caffeine may reduce the risk of squamous cell and basal cell carcinomas among Chinese in Singapore.
http://bit.ly/2WJpLHF
Recommendations for the definition, evaluation, and treatment of nail psoriasis in adult patients with no or mild skin psoriasis: a dermatologist and nail expert group consensus
Nail involvement in psoriasis is common, and the severity of it does not always parallel the intensity of cutaneous disease.We created a consensus group, of which the aim was to provide practical recommendations for the treatment of nail psoriasis in patients without skin psoriasis, or with mild skin lesions with no indication for a systemic treatment. This collaborative process was conducted by an international panel of dermatologists with special expertise in nail disorders, using a formal consensus methodology.
http://bit.ly/2t70Pw4
Assessment of ventilation noise impact from metro depot with over-track platform structure on workers and nearby inhabitants
Abstract
In order to alleviate the shortage of land use accompanied with urbanization, over-track building complexes above metro depots are developed rapidly in China, resulting in the larger mechanical ventilation needs in the metro depot. Excessive noise exposure caused by the huge ventilation system will bring serious impacts on the health of workers in the metro depot. This research intends to evaluate the noise annoyance in the metro depot and the noise influences on adjacent residential buildings by the ventilation system. A questionnaire survey of 100 people working in a metro depot of Guangzhou Metro Line 6 was conducted, and field measurements inside the metro depot and inside adjacent residential buildings were carried out. The environmental noise level in the metro depot and the ventilation fan–induced noise level inside adjacent residential buildings exceed the corresponding criterion limit of China. Dose-response relationship modeled by logistic function was used to assess the noise annoyance, which is found underestimating the percentage of "Annoyed" (% A) and percentage of "Little Annoyed" (% LA) of staffs in the metro depot, especially for the % LA. This may be attributed to the reducing reliability of dose-effect curves as the Ldn is higher than 65 dB(A). In order to alleviate the noise impact, noise-controlling measures need to be took. However, traditional noise-controlling measures cannot solve low-frequency noise disturbance.
http://bit.ly/2HQJAZT
Integration of Melatonin Related Redox Homeostasis, Aging, and Circadian Rhythm
Rejuvenation Research, Ahead of Print.
http://bit.ly/2WFKX14
Whats Bred in the Bone: Calcium Channels in Lymphocytes [BRIEF REVIEWS]
Calcium (Ca2+) is an important second messenger in lymphocytes and is essential in regulating various intracellular pathways that control critical cell functions. Ca2+ channels are located in the plasma membrane and intracellular membranes, facilitating Ca2+ entry into the cytoplasm. Upon Ag receptor stimulation, Ca2+ can enter the lymphocyte via the Ca2+ release-activated Ca2+ channel found in the plasma membrane. The increase of cytosolic Ca2+ modulates signaling pathways, resulting in the transcription of target genes implicated in differentiation, activation, proliferation, survival, and apoptosis of lymphocytes. Along with Ca2+ release-activated Ca2+ channels, several other channels have been found in the membranes of T and B lymphocytes contributing to key cellular events. Among them are the transient receptor potential channels, the P2X receptors, voltage-dependent Ca2+ channels, and the inositol 1,4,5-trisphosphate receptor as well as the N-methyl-d-aspartate receptors. In this article, we review the contributions of these channels to mediating Ca2+ currents that drive specific lymphocyte functions.
http://bit.ly/2UG7WHs
Leishmania donovani Induces Autophagy in Human Blood-Derived Neutrophils [INFECTIOUS DISEASE AND HOST RESPONSE]
Neutrophils, the essential components of the innate immune system, are recruited in large numbers to the pathogen site of entry. Several pathogens induce neutrophil autophagy; however, function of autophagic events during Leishmania parasite infection remain unknown. In this article, we report a finding that is new, to our knowledge, of how Leishmania-induced human polymorphonuclear neutrophil (hPMN) autophagy regulates the silent mode of parasite transfer to macrophages by influencing the engulfment of infected cells. Leishmania infection induced a time-dependent autophagy increase responsive to block by 3-methyladenine but sensitive to ULK1/2 inhibition only after 3 h. This suggested the prevalence of canonical autophagy during later hours, ULK1/2 inhibition being able to block only canonical autophagy. Interaction of Rubicon and Beclin-1 at 1 h postinfection affirmed the prevalence of noncanonical autophagy during early infection. There was a reduction in macrophage uptake of parasite-exposed hPMNs treated with 3-methyladenine or ULK1/2 inhibitor, suggesting the involvement of both noncanonical and canonical autophagy in neutrophil engulfment. Autophagy inducer rapamycin augmented neutrophil engulfment by macrophages. Redistribution of hPMN surface CD47 encouraged neutrophil uptake. Activation of ERK, phosphoinositide 3-kinase, and NADPH oxidase–mediated reactive oxygen species generation were induced after parasite binding. The lpg1-knockout parasites expressing defective lipophosphoglycan did not induce autophagy, indicating that lipophosphoglycan is necessary for interaction with the neutrophils. Autophagy induction was TLR2/4 independent because the receptor blockade did not interfere with infection-induced autophagy. In summary, the engulfment of neutrophils by the macrophages was influenced by the escalation of hPMN autophagy, which is an important event during Leishmania infection.
http://bit.ly/2UE1hgT
A Prime-Pull-Amplify Vaccination Strategy To Maximize Induction of Circulating and Genital-Resident Intraepithelial CD8+ Memory T Cells [MUCOSAL IMMUNOLOGY]
Recent insight into the mechanisms of induction of tissue-resident memory (TRM) CD8+ T cells (CD8+ TRM) enables the development of novel vaccine strategies against sexually transmitted infections. To maximize both systemic and genital intraepithelial CD8+ T cells against vaccine Ags, we assessed combinations of i.m. and intravaginal routes in heterologous prime-boost immunization regimens with unrelated viral vectors. Only i.m. prime followed by intravaginal boost induced concomitant strong systemic and intraepithelial genital-resident CD8+ T cell responses. Intravaginal boost with vectors expressing vaccine Ags was far superior to intravaginal instillation of CXCR3 chemokine receptor ligands or TLR 3, 7, and 9 agonists to recruit and increase the pool of cervicovaginal CD8+ TRM. Transient Ag presentation increased trafficking of cognate and bystander circulating activated, but not naive, CD8+ T cells into the genital tract and induced in situ proliferation and differentiation of cognate CD8+ TRM. Secondary genital CD8+ TRM were induced in the absence of CD4+ T cell help and shared a similar TCR repertoire with systemic CD8+ T cells. This prime-pull-amplify approach elicited systemic and genital CD8+ T cell responses against high-risk human papillomavirus type 16 E7 oncoprotein and conferred CD8-mediated protection to a vaccinia virus genital challenge. These results underscore the importance of the delivery route of nonreplicating vectors in prime-boost immunization to shape the tissue distribution of CD8+ T cell responses. In this context, the importance of local Ag presentation to elicit genital CD8+ TRM provides a rationale to develop novel vaccines against sexually transmitted infections and to treat human papillomavirus neoplasia.
http://bit.ly/2UD9nX3
Characterization of Subpopulations of Chicken Mononuclear Phagocytes That Express TIM4 and CSF1R [INNATE IMMUNITY AND INFLAMMATION]
The phosphatidylserine receptor TIM4, encoded by TIMD4, mediates the phagocytic uptake of apoptotic cells. We applied anti-chicken TIM4 mAbs in combination with CSF1R reporter transgenes to dissect the function of TIM4 in the chick (Gallus gallus). During development in ovo, TIM4 was present on the large majority of macrophages, but expression became more heterogeneous posthatch. Blood monocytes expressed KUL01, class II MHC, and CSF1R-mApple uniformly. Around 50% of monocytes were positive for surface TIM4. They also expressed many other monocyte-specific transcripts at a higher level than TIM4– monocytes. In liver, highly phagocytic TIM4hi cells shared many transcripts with mammalian Kupffer cells and were associated with uptake of apoptotic cells. Although they expressed CSF1R mRNA, Kupffer cells did not express the CSF1R-mApple transgene, suggesting that additional CSF1R transcriptional regulatory elements are required by these cells. By contrast, CSF1R-mApple was detected in liver TIM4lo and TIM4– cells, which were not phagocytic and were more abundant than Kupffer cells. These cells expressed CSF1R alongside high levels of FLT3, MHCII, XCR1, and other markers associated with conventional dendritic cells in mice. In bursa, TIM4 was present on the cell surface of two populations. Like Kupffer cells, bursal TIM4hi phagocytes coexpressed many receptors involved in apoptotic cell recognition. TIM4lo cells appear to be a subpopulation of bursal B cells. In overview, TIM4 is associated with phagocytes that eliminate apoptotic cells in the chick. In the liver, TIM4 and CSF1R reporters distinguished Kupffer cells from an abundant population of dendritic cell–like cells.
http://bit.ly/2UE1ctB
Cutting Edge: HDAC3 Protects Double-Positive Thymocytes from P2X7 Receptor-Induced Cell Death [CUTTING EDGE]
Intricate life-versus-death decisions are programmed during T cell development, and the regulatory mechanisms that coordinate their activation and repression are still under investigation. In this study, HDAC3-deficient double-positive (DP) thymocytes exhibit a severe decrease in numbers. The thymic cortex is rich in ATP, which is released by macrophages that clear apoptotic DP thymocytes that fail to undergo positive selection. We demonstrate that HDAC3 is required to repress expression of the purinergic receptor P2X7 to prevent DP cell death. HDAC3-deficient DP thymocytes upregulate the P2X7 receptor, increasing sensitivity to ATP-induced cell death. P2rx7/HDAC3-double knockout mice show a partial rescue in DP cell number. HDAC3 directly binds to the P2rx7 enhancer, which is hyperacetylated in the absence of HDAC3. In addition, RORt binds to the P2rx7 enhancer and promotes P2X7 receptor expression in the absence of HDAC3. Therefore, HDAC3 is a critical regulator of DP thymocyte survival and is required to suppress P2X7 receptor expression.
http://bit.ly/2Sf6BLa
Cadmium Induces Glomerular Endothelial Cell-Specific Expression of Complement Factor H via the -1635 AP-1 Binding Site [INNATE IMMUNITY AND INFLAMMATION]
Cadmium (Cd) is an environmental toxin that induces nephrotoxicity. Complement factor H (CFH), an inhibitor of complement activation, is involved in the pathogenesis of various renal diseases. In this study, we investigated the effects of Cd on CFH production by the kidney. In C57B6/J mice, an increased CFH level was found in renal blood and glomerular endothelial cells after Cd treatment. In vitro, Cd induces an increased CFH secretion and mRNA expression in human renal glomerular endothelial cells but not in human podocytes or human mesangial cells. Cd activates the JNK pathway and increases c-Jun and c-Fos in human renal glomerular endothelial cells. A JNK inhibitor, SP600125, specifically abolishes Cd-induced CFH production. By chromatin immunoprecipitation assay and EMSA, the –1635 AP-1 motif on human CFH promoter was identified as the binding element for c-Jun and c-Fos. In a luciferase activity assay, mutation of the AP1 site eliminates Cd-induced increase of CFH promoter activity. Thus, the –1635 AP-1 motif on the CFH promoter region mediates Cd-inducible CFH gene expression.
http://bit.ly/2UHzEDO
Cutting Edge: ICOS-Deficient Regulatory T Cells Display Normal Induction of Il10 but Readily Downregulate Expression of Foxp3 [CUTTING EDGE]
The ICOS pathway has been implicated in the development and functions of regulatory T (Treg) cells, including those producing IL-10. Treg cell–derived IL-10 is indispensable for the establishment and maintenance of intestinal immune homeostasis. We examined the possible involvement of the ICOS pathway in the accumulation of murine colonic Foxp3- and/or IL-10–expressing cells. We show that ICOS deficiency does not impair induction of IL-10 by intestinal CD4 T cells but, instead, triggers substantial reductions in gut-resident and peripherally derived Foxp3+ Treg cells. ICOS deficiency is associated with reduced demethylation of Foxp3 CNS2 and enhanced loss of Foxp3. This instability significantly limits the ability of ICOS-deficient Treg cells to reverse ongoing inflammation. Collectively, our results identify a novel role for ICOS costimulation in imprinting the functional stability of Foxp3 that is required for the retention of full Treg cell function in the periphery.
http://bit.ly/2UE1vEL
Neutrophil Cathepsin G Regulates Dendritic Cell Production of IL-12 during Development of CD4 T Cell Responses to Antigens in the Skin [ALLERGY AND OTHER HYPERSENSITIVITIES]
Contact hypersensitivity (CHS) is a CD8 T cell–mediated response to hapten skin sensitization and challenge. Sensitization of wild-type (WT) mice induces hapten-reactive effector CD8 T cells producing IFN- and IL-17– and IL-4–producing CD4 T cells that cannot mediate CHS. Although CXCR2-dependent Ly6G+ (neutrophil) cell recruitment into hapten-challenged skin is required to direct effector CD8 T cell infiltration into the challenge site to elicit CHS, 2,4-dinitrofluorobenezene (DNFB) sensitization of CXCR2–/– mice and neutrophil-depleted WT mice induced both hapten-reactive CD4 and CD8 T cells producing IFN- and IL-17. CD4 T cell–mediated CHS responses were not generated during DNFB sensitization of neutrophil-depleted WT mice treated with anti–IL-12 mAb or neutrophil-depleted IL-12–/– mice. Neutrophil depletion during DNFB sensitization of WT mice markedly increased IL-12–producing hapten-primed dendritic cell numbers in the skin-draining lymph nodes. Sensitization of mice lacking the neutrophil serine protease cathepsin G (CG)–induced hapten-reactive CD4 and CD8 T cells producing IFN- and IL-17 with elevated and elongated CHS responses to DNFB challenge. Induction of CHS effector CD4 T cells producing IFN- in neutrophil-depleted WT mice was eliminated by s.c. injection of active, but not inactivated, CG during sensitization. Thus, hapten skin sensitization induces neutrophil release of CG that systemically inhibits hapten-presenting dendritic cell production of IL-12 and the development of hapten-reactive CD4 T cells to IFN-–producing CHS effector cells.
http://bit.ly/2SbzRCo
Immune Cell Infiltration into the Eye Is Controlled by IL-10 in Recoverin-Induced Autoimmune Retinopathy [AUTOIMMUNITY]
Autoimmune retinopathy (AIR) is a treatable condition that manifests in acute and progressive vision loss in patients. It has recently been determined that AIR is associated with an imbalance of TH1 versus regulatory T cell immunity toward the retinal protein, recoverin. This study describes a new murine model to understand the immunopathology of AIR and its association with T cell responses toward recoverin. Immunization of C57BL/6 mice with recoverin resulted in ocular inflammation including infiltration of CD4+ and CD8+ T lymphocytes, B cells, and CD11b+Ly6C+ inflammatory monocytes in the eyes. Production of IFN- and IL-17 from T cells was exacerbated in IL-10 knockout (KO) mice and kinetics of disease development was accelerated. Infiltration of T cells and inflammatory monocytes into the eyes dramatically increased in recoverin-immunized IL-10 KO mice. An immunodominant peptide of recoverin, AG-16, was capable of inducing disease in IL-10 KO mice and resulted in expansion of AG-16 tetramer-specific CD4+ T cells in lymphoid organs and eyes. Adoptive transfer of recoverin-stimulated cells into naive mice was sufficient to induce AIR, and immunization of B cell–deficient mice led to a milder form of the disease. This model supports the hypothesis that recoverin-specific T cell responses are major drivers of AIR pathogenesis and that IL-10 is an important factor in protection.
http://bit.ly/2UE1u3F
Angiogenic Host Defense Peptide AG-30/5C and Bradykinin B2 Receptor Antagonist Icatibant Are G Protein Biased Agonists for MRGPRX2 in Mast Cells [INNATE IMMUNITY AND INFLAMMATION]
AG-30/5C is an angiogenic host defense peptide that activates human mast cells (MC) via an unknown mechanism. Using short hairpin RNA–silenced human MC line LAD2 and stably transfected RBL-2H3 cells, we demonstrate that AG-30/5C induces MC degranulation via Mas-related G protein–coupled receptor X2 (MRGPRX2). Most G protein–coupled receptors signal via parallel and independent pathways mediated by G proteins and β-arrestins. AG-30/5C and compound 48/80 induced similar maximal MC degranulation via MRGPRX2, which was abolished by pertussis toxin. However, compound 48/80 induced a robust β-arrestin activation as determined by transcriptional activation following arrestin translocation (Tango), but AG-30/5C did not. Overnight culture of MC with compound 48/80 resulted in reduced cell surface MRGPRX2 expression, and this was associated with a significant decrease in subsequent MC degranulation in response to compound 48/80 or AG-30/5C. However, AG-30/5C pretreatment had no effect on cell surface MRGPRX2 expression or degranulation in response to compound 48/80 or AG-30/5C. Icatibant, a bradykinin B2 receptor antagonist, promotes MC degranulation via MRGPRX2 and causes pseudoallergic drug reaction. Icatibant caused MC degranulation via a pertussis toxin–sensitive G protein but did not activate β-arrestin. A screen of the National Institutes of Health Clinical Collection library led to the identification of resveratrol as an inhibitor of MRGPRX2. Resveratrol inhibited compound 48/80–induced Tango and MC degranulation in response to compound 48/80, AG-30/5C, and Icatibant. This study demonstrates the novel finding that AG-30/5C and Icatibant serve as G protein–biased agonists for MRGPRX2, but compound 48/80 signals via both G protein and β-arrestin with distinct differences in receptor regulation.
http://bit.ly/2UAmVmi
The Autoimmune Susceptibility Gene C5orf30 Regulates Macrophage-Mediated Resolution of Inflammation [AUTOIMMUNITY]
Genetic variants in C5orf30 have been associated with development of the autoimmune conditions primary biliary cirrhosis and rheumatoid arthritis. In rheumatoid arthritis, C5orf30 expression is cell-specific, with highest expression found in macrophages and synovial fibroblasts. C5orf30 is highly expressed in inflamed joints and is a negative regulator of tissue damage in a mouse model of inflammatory arthritis. Transcriptomic analysis from ultrasound-guided synovial biopsy of inflamed joints in a well characterized clinical cohort of newly diagnosed, disease-modifying antirheumatic drugs–naive rheumatoid arthritis patients was used to determine the clinical association of C5orf30 expression with disease activity. A combined molecular and computational biology approach was used to elucidate C5orf30 function in macrophages both in vitro and in vivo. Synovial expression of C5orf30 is inversely correlated with both clinical measures of rheumatoid arthritis disease activity and with synovial TNF mRNA expression. C5orf30 plays a role in regulating macrophage phenotype and is differentially turned over in inflammatory and anti-inflammatory macrophages. Inhibition of C5orf30 reduces wound healing/repair–associated functions of macrophages, reduces signaling required for resolution of inflammation, and decreases secretion of anti-inflammatory mediators. In an animal model of wound healing (zebrafish), C5orf30 inhibition increases the recruitment of macrophages to the wound site. Finally, we demonstrate that C5orf30 skews macrophage immunometabolism, demonstrating a mechanism for C5orf30-mediated immune regulation.
http://bit.ly/2S7WpUu
Growth Factor-like Gene Regulation Is Separable from Survival and Maturation in Antibody-Secreting Cells [SYSTEMS IMMUNOLOGY]
Recurrent mutational activation of the MAP kinase pathway in plasma cell myeloma implicates growth factor–like signaling responses in the biology of Ab-secreting cells (ASCs). Physiological ASCs survive in niche microenvironments, but how niche signals are propagated and integrated is poorly understood. In this study, we dissect such a response in human ASCs using an in vitro model. Applying time course expression data and parsimonious gene correlation network analysis (PGCNA), a new approach established by our group, we map expression changes that occur during the maturation of proliferating plasmablast to quiescent plasma cell under survival conditions including the potential niche signal TGF-β3. This analysis demonstrates a convergent pattern of differentiation, linking unfolded protein response/endoplasmic reticulum stress to secretory optimization, coordinated with cell cycle exit. TGF-β3 supports ASC survival while having a limited effect on gene expression including upregulation of CXCR4. This is associated with a significant shift in response to SDF1 in ASCs with amplified ERK1/2 activation, growth factor–like immediate early gene regulation and EGR1 protein expression. Similarly, ASCs responding to survival conditions initially induce partially overlapping sets of immediate early genes without sustaining the response. Thus, in human ASCs growth factor–like gene regulation is transiently imposed by niche signals but is not sustained during subsequent survival and maturation.
http://bit.ly/2UGlTVP
A Functional Idiotype/Anti-Idiotype Network Is Active in Genetically Gluten-Intolerant Individuals Negative for Both Celiac Disease-Related Intestinal Damage and Serum Autoantibodies [AUTOIMMUNITY]
An unbalance between Abs that recognize an autoantigen (idiotypes; IDs) and Igs that bind such Abs (anti-IDs) is considered a functional event in autoimmune disorders. We investigated the presence of an ID/anti-ID network in celiac disease (CD), a condition in which antitissue transglutaminase 2 (TG2) Abs are suspected to contribute to CD pathogenesis. To characterize the ID side, we reproduced by in vitro yeast display the intestine-resident Abs from CD and control patients. These TG2-specific IDs were used to identify potential anti-IDs in the serum. We observed elevated titers of anti-IDs in asymptomatic patients with predisposition to CD and demonstrated that anti-ID depletion from the serum restores a detectable humoral response against TG2. Our study provides an alternative approach to quantify CD-related autoantibodies in cases that would be defined "negative serology" with current diagnostic applications. Therefore, we suggest that developments of this technology could be designed for perspective routine tests.
http://bit.ly/2UG7OHY
Cyclic Dinucleotide-Adjuvanted Dengue Virus Nonstructural Protein 1 Induces Protective Antibody and T Cell Responses [IMMUNOTHERAPY AND VACCINES]
Endothelial dysfunction and vascular leak, pathogenic hallmarks of severe dengue disease, are directly triggered by dengue virus (DENV) nonstructural protein 1 (NS1). Previous studies have shown that immunization with NS1, as well as passive transfer of NS1-immune serum or anti-NS1 mAb, prevent NS1-mediated lethality in vivo. In this study, we evaluated the immunogenicity and protective capacity of recombinant DENV NS1 administered with cyclic dinucleotides (CDNs), potent activators of innate immune pathways and highly immunogenic adjuvants. Using both wild-type C57BL/6 mice and IFN-α/β receptor–deficient mice, we show that NS1-CDN immunizations elicit serotype-specific and cross-reactive Ab and T cell responses. Furthermore, NS1-CDN vaccinations conferred significant homotypic and heterotypic protection from DENV2-induced morbidity and mortality. In addition, we demonstrate that high anti-NS1 Ab titers are associated with protection, supporting the role of humoral responses against DENV NS1 as correlates of protection. These findings highlight the potential of CDN-based adjuvants for inducing Ab and T cell responses and validate NS1 as an important candidate for dengue vaccine development.
http://bit.ly/2S7WpDY
Histone H3K27 Demethylase Negatively Controls the Memory Formation of Antigen-Stimulated CD8+ T Cells [IMMUNE REGULATION]
Although the methylation status of histone H3K27 plays a critical role in CD4+ T cell differentiation and its function, the role of Utx histone H3K27 demethylase in the CD8+ T cell–dependent immune response remains unclear. We therefore generated T cell–specific Utxflox/flox Cd4-Cre Tg (Utx KO) mice to determine the role of Utx in CD8+ T cells. Wild-type (WT) and Utx KO mice were infected with Listeria monocytogenes expressing OVA to analyze the immune response of Ag-specific CD8+ T cells. There was no significant difference in the number of Ag-specific CD8+ T cells upon primary infection between WT and Utx KO mice. However, Utx deficiency resulted in more Ag-specific CD8+ T cells upon secondary infection. Adoptive transfer of Utx KO CD8+ T cells resulted in a larger number of memory cells in the primary response than in WT. We observed a decreased gene expression of effector-associated transcription factors, including Prdm1 encoding Blimp1, in Utx KO CD8+ T cells. We confirmed that the trimethylation level of histone H3K27 in the Prdm1 gene loci in the Utx KO cells was higher than in the WT cells. The treatment of CD8+ T cells with Utx-cofactor α-ketoglutarate hampered the memory formation, whereas Utx inhibitor GSK-J4 enhanced the memory formation in WT CD8+ T cells. These data suggest that Utx negatively controls the memory formation of Ag-stimulated CD8+ T cells by epigenetically regulating the gene expression. Based on these findings, we identified a critical link between Utx and the differentiation of Ag-stimulated CD8+ T cells.
http://bit.ly/2S6u7ts
Ablation and Inhibition of the Immunoproteasome Catalytic Subunit LMP7 Attenuate Experimental Abdominal Aortic Aneurysm Formation in Mice [INNATE IMMUNITY AND INFLAMMATION]
Low–molecular mass protein 7 (LMP7) is a proteolytic subunit of the immunoproteasome that is involved in regulating inflammatory responses. However, the role of LMP7 in the pathogenesis of abdominal aortic aneurysm (AAA) remains unknown. In this study, ApoE knockout (KO) or LMP7/ApoE double KO (dKO) mice were infused with angiotensin II (Ang II, 1000 ng/kg per minute) for up to 28 d. We found that LMP7 expression was significantly upregulated in AAA tissues from ApoE KO mice and human patients. Moreover, Ang II infusion markedly increased the incidence and severity of AAA in ApoE KO mice, which was considerably reduced in LMP7/ApoE dKO mice. Histological alterations, including aortic wall thickening, collagen deposition, elastin fragmentation, and vascular smooth muscle cell apoptosis in AAA tissue of ApoE KO mice, were also significantly attenuated in LMP7/ApoE dKO mice. Interestingly, LMP7/ApoE dKO mice showed a marked reduction of infiltration of CD3+ T cells, especially CD4+ T cells in AAA tissues compared with ApoE KO mice. Moreover, ablation of LMP7 substantially inhibited the differentiation of CD4+ T cells into Th1 and Th17 cells by reducing the activation of multiple transcriptional factors. We also investigated the effects of an LMP7-specific inhibitor PR-957 (also known as ONX 0914) on AAA formation in ApoE KO mice. PR-957 treatment could reduce the AAA incidence and severity. In conclusion, our results provide, to our knowledge, novel evidence that ablation or pharmacological inhibition of LMP7 attenuates Ang II–induced AAA formation, and LMP7 might be a novel therapeutic target for treating AAA in humans.
http://bit.ly/2SdC3sX
ADAR1 Is Required for Dendritic Cell Subset Homeostasis and Alveolar Macrophage Function [IMMUNE REGULATION]
RNA editing by adenosine deaminases acting on dsRNA (ADAR) has become of increasing medical relevance, particularly because aberrant ADAR1 activity has been associated with autoimmunity and malignancies. However, the role of ADAR1 in dendritic cells (DC), representing critical professional APCs, is unknown. We have established conditional murine CD11c Cre-mediated ADAR1 gene ablation, which did not induce general apoptosis in CD11c+ cells but instead manifests in cell type–specific effects in DC subpopulations. Bone marrow–derived DC subset analysis revealed an incapacity to differentiate CD103 DC+ in both bulk bone marrow and purified pre-DC lineage progenitor assays. ADAR1 deficiency further resulted in a preferential systemic loss of CD8+/CD103+ DCs, revealing critical dependency on ADAR1, whereas other DC subpopulations were moderately affected or unaffected. Additionally, alveolar macrophages were depleted and dysfunctional, resembling pulmonary alveolar proteinosis. These results reveal an unrecognized role of ADAR1 in DC subset homeostasis and unveils the cell type–specific effects of RNA editing.
http://bit.ly/2UE1oJl
C1s Inhibition by BIVV009 (Sutimlimab) Prevents Complement-Enhanced Activation of Autoimmune Human B Cells In Vitro [INNATE IMMUNITY AND INFLAMMATION]
The classical pathway of complement (CP) can mediate C3 opsonization of Ags responsible for the costimulation and activation of cognate B lymphocytes. In this manner, the complement system acts as a bridge between the innate and adaptive immune systems critical for establishing a humoral response. However, aberrant complement activation is often observed in autoimmune diseases in which C3 deposition on self-antigens may serve to activate self-reactive B cell clones. In this study, we use BIVV009 (Sutimlimab), a clinical stage, humanized mAb that specifically inhibits the CP-specific serine protease C1s to evaluate the impact of upstream CP antagonism on activation and proliferation of normal and autoimmune human B cells. We report that BIVV009 significantly inhibited complement-mediated activation and proliferation of primary human B cells. Strikingly, CP antagonism suppressed human Ig–induced activation of B cells derived from patients with rheumatoid arthritis. These results suggest that clinical use of CP inhibitors in autoimmune patients may not only block complement-mediated tissue damage, but may also prevent the long-term activation of autoimmune B cells and the production of autoantibodies that contribute to the underlying pathologic condition of these diseases.
http://bit.ly/2S9q3ca
Lack of Ikaros Deregulates Inflammatory Gene Programs in T Cells [IMMUNE REGULATION]
CD4 Th cells are organizers of the immune response, directing other immune cells to initiate and maintain effective humoral and cellular immunity. CD4 T cells differentiate into distinct Th effector or regulatory subsets in response to signals delivered to them during the course of infection. Ikaros is a transcription factor that is expressed in blood cells from the level of the hematopoietic stem cell. It is required for normal thymic T cell development and serves as a tumor suppressor, as lack of Ikaros in developing lymphoid cells results in leukemia. To study the role of Ikaros in CD4 T cell differentiation and function, an Ikaros conditional knockout mouse was developed such that Ikaros expression was deleted specifically in mature T cells, thus avoiding defects observed in germline Ikaros mutant mice. Using this model system, we have shown that in the absence of Ikaros, CD4 T cells are able to attain Th1, Th2, and Th17, but not inducible regulatory T, cell fates. However, they show enhanced expression of a cohort of proinflammatory cytokines, resulting in differentiation of Th17 cells with a phenotype that has been associated with autoimmunity and pathological inflammation. In addition, we define Ikaros as a repressor of the gene program associated with the response to type I IFNs, another key pathway whose deregulation is linked to autoimmunity. Taken together, these data definitively define Ikaros as a critical regulator at the center of the inflammatory response in T cells and highlight a potential role in suppressing autoimmunity.
http://bit.ly/2SbtaAi
Impact of regulatory focus on express packaging waste recycling behavior: moderating role of psychological empowerment perception
Abstract
To effectively solve environmental pollution and resource waste problems caused by the rapid growth of express packaging waste, government intervention is needed in the separation and recycling of household waste at the source. Considering the correlation between behavior and individual psychological preference and concerns, this study administered a questionnaire survey (N = 847) and used factor analysis, hierarchical regression, and sensitivity analysis to evaluate the responses and determine the influence of individual focus tendency and empowerment perception on waste recycling behavior. The results showed that individuals with a high prevention focus or a high promotion focus were more likely to have good waste recycling behaviors. Furthermore, the higher the psychological perception of waste recycling empowerment (reflected in the meaning, competence, choice, and impact), the more inclined an individual to participate in recycling and waste reduction activities. In terms of interaction effect, psychological empowerment perception and its dimensions can positively moderate the effect of promotion focus on waste recycling behaviors. In other words, psychological empowerment perception acts as an "amplifier," and its dimension of meaning was the most important moderating variable. The study results supported policy suggestions to promote individuals' active participation in waste source separation and recycling activities.
http://bit.ly/2Dc5jWE
Multi-objective optimized scheduling model for hydropower reservoir based on improved particle swarm optimization algorithm
Abstract
In order to make hydropower station's development and operation harmonious with ecological protection, the optimal operation of hydropower stations to meet the needs of ecological protection is studied. Firstly, the ecological protection function of river course is defined according to the minimum ecological runoff and suitable ecological runoff. Then, a multi-objective optimal running model of reservoir which can maximize the capacity of ecological protection and generation is proposed. Finally, an improved multi-objective particle swarm optimization algorithm (MOPSO), which can construct a neighborhood for each particle and choose the neighborhood optimal solution by adopting self-organizing mapping (SOM) method, is proposed to solve the model. The model is applied to the Shui-Kou Hydropower Station in Minjiang, China. The results show that the model can get the optimal schedule with balanced consideration of ecological benefits and power generation benefits, which has not a great impact on the economic benefits of reservoirs while achieving the goal of ecological environment. The research results can provide theoretical basis and concrete scheme reference for reservoir operation.
http://bit.ly/2Gb5BRK
Liver disorders related to exposure to gasoline fumes in male rats and role of fenugreek seed supplementation
Abstract
Progressive effects of inhalation of gasoline fumes on the liver and the protective potential with fenugreek seed supplementation were evaluated in adult male rats. Twenty-four rats were divided into four groups, unexposed control and fenugreek groups, as well as exposed groups to gasoline fumes for 6 h/6 days/week for 10 weeks, with and without supplementation of fenugreek seed powder in food (5%w/w). Exposure to gasoline fumes resulted in a significant elevation in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, total bilirubin, total cholesterol, total triglycerides, and low-density lipoprotein, along with a significant decrease in high-density lipoprotein, total protein, and albumin contents compared to the control. Meanwhile, liver oxidative stress markers, malondialdehyde, hydrogen peroxide, and nitric oxide, were highly detected with decreased antioxidants, superoxide dismutase and catalase. Also, levels of inflammatory markers, interleukin(IL)-1β and IL-6, were significantly elevated with fibrotic markers, transforming growth factor (TGFβ1), fibroblast growth factor (FGF1), and collagen I. Histopathological studies illustrated that rats exposed to gasoline fumes have degenerated hepatocytes with cellular infiltration and necrotic areas, along with remarkable deposition of collagen fibers, suggesting an incidence of liver fibrosis. Administration of fenugreek seeds, rich with antioxidant and anti-inflammatory components, during gasoline exposure showed significant amelioration through suppressing oxidative stress and inflammation.
http://bit.ly/2DbxAwH
HSPF-based watershed-scale water quality modeling and uncertainty analysis
Abstract
This paper presents findings on uncertainties, introduced through digital elevation model (DEM) resolution and DEM resampling, in watershed-scale flow and water quality (NO3, P, and total suspended sediment) simulations. The simulations were performed using the Better Assessment Science Integrating Point and Nonpoint Sources/Hydrological Simulation Program Fortran watershed modeling system for two representative study watersheds delineated with both the original DEMs of four different resolutions (including 3.5, 10, 30, and 100 m) and the resampled DEMs of three different resolutions (including 10, 30, and 100 m), creating 14 simulation scenarios. Parameter uncertainties were quantified by means of the GLUE approach and compared to input data uncertainties. Results from the 14 simulation scenarios showed that there was a common increasing trend in errors of simulated flow and water quality parameters when the DEM resolution became coarser. The errors involved in the watershed with a mild slope were found to be substantially (up to 10 times) greater than those of the other watershed with a relatively steep slope. It was also found that sediment was the most sensitive and NO3 was the least sensitive parameters to the variation in DEM resolution, as evidenced by the maximum normalized root mean square error (NRMSE) of 250% in the simulated sediment concentration and 11% in the simulated NO3 concentration, respectively. Moreover, results achieved from the resampled (particularly coarser) DEMs were significantly different from corresponding ones from original DEMs. By comparing uncertainties from different sources, it was found that the parameter-induced uncertainties were higher than the resolution-induced uncertainties particularly in simulated NO3 and P concentrations for studied watersheds. The findings provide new insights into the sensitivity and uncertainty of water quality parameters and their simulation results, serving as the guidelines for developing and implementing water quality management and watershed restoration plans.
http://bit.ly/2Gaz0vh
Migration characteristics and toxicity evaluation of heavy metals during the preparation of lightweight aggregate from sewage sludge
Abstract
A lightweight aggregate (LWA) was manufactured from municipal sewage sludge, gangue, and coal ash. The product performance and environmental safety of the sintered material were evaluated by changing the sludge blending ratio and sintering temperature. The distribution and migratory transformation characteristics of heavy metals in LWA were examined by BCR sequential extraction in combination with inductively coupled plasma optical emission spectrometry (ICP-OES). The environmental safety performance of LWA was comprehensively evaluated by the OPTI index for the first time. The leaching concentration of the heavy metals Pb, Ni, Cu, and Zn in raw materials without sintering reached 1.17, 1.6, 7.84, and 7.56 mg/L, respectively, far exceeding the regulatory threshold value. At 1250 °C, sintering with 60% sludge content resulted in Cu and Zn leaching concentrations of only 0.41 mg/L and 0.37 mg/L, respectively. Furthermore, a big portion of heavy metals were in the residual fraction of sintered LWA. The proportion of comprehensive pollutant toxicity index is only 199.17. Additionally, the mechanical properties of sintered LWA exceed the standards stipulated in the GB/T1743.1-2010 standard. Using sewage sludge to manufacture lightweight aggregate is not only environmentally safe but also produces LWA with good engineering characteristics.
http://bit.ly/2D8qHwc
Characteristics and management modes of domestic waste in rural areas of developing countries: a case study of China
Abstract
A huge accumulation of domestic waste has caused serious environmental contamination in rural areas of developing countries (RADIC). The characteristics and management of domestic waste are carefully discussed, based on field surveys and a literature review. The results indicate that the generation in most of RADIC is less than the median of 0.521 kg day−1 per capita in China, and much smaller than in rural areas of developed countries (RADEC). Organic waste and inert waste with an accumulative mass percentage of 72.31% are dominant components of domestic waste in the rural areas of China. There are trends of increasing amounts of kitchen waste, paper/cardboard, and plastic/rubber and a decreasing trend of ash waste. The RADIC composition of domestic waste had a high content of organic waste and a low content of recyclable waste compared to the RADEC. Domestic waste has good compressibility and a light bulk density ranging from 40 to 650 kg m−3. The moisture, ash, combustible, and calorific values of domestic waste were 53.31%, 18.03%, 28.67%, and 5368 kJ kg−1, respectively. The domestic waste has an abundance of nutrients including organic matter (39.05%), nitrogen (1.02%), phosphorus (0.50%), and potassium (1.42%). In RADIC, domestic waste can be used as an agricultural manure only after it has been collected and sorted for the potential risk of heavy metal accumulation. Based on these characteristics of domestic waste and the different situations of rural areas, four waste management modes including centralized treatment, decentralized treatment, group treatment, and mobile treatment are designed and discussed.
http://bit.ly/2GbBlpA
The efficacy and limitations of USI for diagnosing TMJ internal derangements
Abstract
Introduction
This study was conducted to determine the effectiveness of ultrasonographic imaging for diagnosing temporomandibular joint internal derangements.
Materials and methods
Ultrasonographic and magnetic resonance imaging scans of temporomandibular joints were obtained bilaterally in 55 patients who had temporomandibular joint disorders and who were diagnosed with temporomandibular joint internal derangements following a clinical examination. Diagnostic accuracy of ultrasonographic imaging was assessed considering magnetic resonance imaging as the gold standard method.
Results
When the results of ultrasonographic imaging and magnetic resonance imaging were compared, the diagnostic accuracy of ultrasonographic imaging was 0.81 for detecting TMJ disc displacement. The diagnostic accuracy of ultrasonographic imaging in detecting TMJ disc position was 0.81 in the closed-mouth position and 0.93 in the open-mouth position.
Conclusion
As a noninvasive and reproducible imaging method acquiring dynamic images, ultrasonographic imaging is a successful method in the evaluation of temporomandibular joint disc displacement.
http://bit.ly/2SsxOJn
Levels of horse allergen Equ C 4 in dander and saliva from ten horse breeds
Abstract
Background
Horses are an important source of allergens, but the distribution of horse allergens is poorly understood. Five horse allergens have been identified, Equ c 1‐4 and 6. Equ c 4 seems to be an important allergen, with an IgE‐binding frequency of 77% in horse‐sensitized individuals.
Objectives
The aim of this study was to investigate levels of horse allergen Equ c 4 in dander, saliva and urine from ten horse breeds.
Method: The study population included 170 horses (87 mares, 27 stallions, 56 geldings) from ten breeds. Horse dander, saliva and urine samples were collected. Levels of horse allergen Equ c 4 were quantified using a two‐site sandwich ELISA (mAb 103 and 14G4) and were expressed as Equ c 4 U/μg protein.
Results
The horse allergen Equ c 4 was present in all dander and saliva samples from ten horse breeds, with high within‐breed and inter‐breed variations; GM values were 639 Equ c 4 U /μg protein (range 5 – 15264) for dander and 39.5 (4 – 263) for saliva. Equ c 4 was found in 19/21 urine samples. Adjusted for age, sex and changes over time, no differences between breeds could be seen in dander, while in saliva the North Swedish horse showed lower levels of Equ c 4 than any other breed. The levels of Equ c 4 protein in dander and saliva were significantly higher in samples from stallions compared to mares and geldings, independent of breed.
Conclusions & Clinical Relevance
The results show a high variability in allergen levels of Equ c 4 in dander and saliva both within and between breeds. Significantly higher levels were found in stallions compared to mares and geldings, independent of breed. Results suggest that none of the horse breeds studied can be recommended for individuals allergic to Equ c 4.
This article is protected by copyright. All rights reserved.
http://bit.ly/2Tvxqar
Alopecic patches of the scalp: a variant of primary cutaneous follicle center B‐cell lymphoma reported in a series of 14 cases
Abstract
Primary cutaneous follicle center lymphoma (PCFCL) is the most frequent primary cutaneous B‐cell lymphoma. It presents usually with erythematous papules, plaques and tumors that predominate on the head, neck and upper trunk. The evolution is indolent but relapses are frequent. Atypical presentations of PCFCL have been occasionally described, such as diffuse facial erythema, one case of scarring alopecia (1), macular lesions, including 2 cases of scarring alopecia (2), miliary agminated papules (3), or extensive telangiectasia of the scalp (4). The incidence and prognosis of these atypical forms are unknown.
This article is protected by copyright. All rights reserved.
http://bit.ly/2WP3U1s
Assessment of acute toxicity and cytotoxicity of fluorescent markers produced by cardanol and glycerol, which are industrial waste, to different biological models
Abstract
The amphyphylic triazoanilines recently synthesized 1-(4-(3-aminophenyl)-1H-1,2,3- triazole-1-yl)-3-(3-pentadecylphenoxy)propan-2-ol (1) and 1-(4-(4-aminophenyl)-1H- 1,2,3-triazole-1-yl)-3-(3-pentadecylphenoxy)propan-2-ol (2), synthesized from cardanol and glycerol, have photophysical properties which allow their use in the development of fluorescent biomarkers with applicability in the biodiesel quality control. Based on this, the present research evaluated the toxic effects of both compounds in different biological models through the investigation of survival and mortality percentages as a measure of acute toxicity on Daphnia similis and Oreochromis niloticus, larvicidal assay against Aedes aegypti, and cytotoxic activity on mammary cells. Results demonstrate that these triazoanilines 1 and 2 have shown low acute toxicity to the biological models investigated in this study up to the following concentrations: 4.0 mg L-1 (D. similis), 4.0 mg L-1 (A. aegypti larvae), 1.0 mg L-1 (O. niloticus), and 1.0 mg mL-1 (mammary cells). This fact suggests the potential for safe use of compounds 1 and 2 as fluorescent markers for the monitoring of biodiesel quality, even in the case of environmental exposure. Besides all of that, the reuse of cardanol and glycerol, both industrial wastes, favors the maintenance of environmental health and is in agreement with the assumptions of green chemistry.
Graphical abstract
ᅟ
http://bit.ly/2SxrRuY
Clinical perspectives in congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase type 2 deficiency
Abstract
Purpose
3β-hydroxysteroid dehydrogenase type 2 deficiency (3βHSD2D) is a very rare variant of congenital adrenal hyperplasia (CAH) causing less than 0.5% of all CAH. The aim was to review the literature.
Methods
PubMed was searched for relevant articles.
Results
3βHSD2D is caused by HSD3B2 gene mutations and characterized by impaired steroid synthesis in the gonads and the adrenal glands and subsequent increased dehydroepiandrosterone (DHEA) concentrations. The main hormonal changes observed in patients with 3βHSD2D are elevated ratios of the Δ5-steroids over Δ4-steroids but molecular genetic testing is recommended to confirm the diagnosis. Several deleterious mutations in the HSD3B2 gene have been associated with salt-wasting (SW) crisis in the neonatal period, while missense mutations have been associated with a non-SW phenotype. Boys may have ambiguous genitalia, whereas girls present with mild or no virilization at birth. The existence of non-classic 3βHSD2D is controversial. In an acute SW crisis, the treatment includes prompt rehydration, correction of hypoglycemia, and parenteral hydrocortisone. Similar to other forms of CAH, glucocorticoid and mineralocorticoid replacement is needed for long-term management. In addition, sex hormone replacement therapy may be required if normal progress through puberty is failing. Little is known regarding possible negative long-term consequences of 3βHSD2D and its treatments, e.g., fertility, final height, osteoporosis and fractures, adrenal and testicular tumor risk, and mortality.
Conclusion
Knowledge is mainly based on case reports but many long-term outcomes could be presumed to be similar to other types of CAH, mainly 21-hydroxylase deficiency, although in 3βHSD2D it seems to be more difficult to suppress the androgens.
http://bit.ly/2GnuWXZ
A deep convolutional neural network for the diagnosis of thyroid nodules on ultrasound
Abstract
Background
We designed a deep convolutional neural network (CNN) to diagnose thyroid malignancy on ultrasound (US) and compared the diagnostic performance of CNN with that of experienced radiologists.
Methods
Between May 2012 and February 2015, 589 thyroid nodules in 519 patients were diagnosed as benign or malignant by surgical excision. Experienced radiologists retrospectively reviewed the US of the thyroid nodules in a test set. CNNs were trained and tested using retrospective data of 439 and 150 US images, respectively. Diagnostic performances were compared between the two groups.
Results
Of the 589 thyroid nodules, 396 were malignant and 193 were benign. The area under the curve (AUC) for diagnosing thyroid malignancy was 0.805‐0.860 for radiologists. The AUCs for diagnosing thyroid malignancy for the three CNNs were 0.845, 0.835, and 0.850. There was no significant difference in AUC between radiologists and CNNs.
Conclusions
CNNs showed comparable diagnostic performance compared to experienced radiologists in differentiating thyroid malignancy on US.
http://bit.ly/2BdGWI7
Clinical perspectives in congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase type 2 deficiency
Abstract
Purpose
3β-hydroxysteroid dehydrogenase type 2 deficiency (3βHSD2D) is a very rare variant of congenital adrenal hyperplasia (CAH) causing less than 0.5% of all CAH. The aim was to review the literature.
Methods
PubMed was searched for relevant articles.
Results
3βHSD2D is caused by HSD3B2 gene mutations and characterized by impaired steroid synthesis in the gonads and the adrenal glands and subsequent increased dehydroepiandrosterone (DHEA) concentrations. The main hormonal changes observed in patients with 3βHSD2D are elevated ratios of the Δ5-steroids over Δ4-steroids but molecular genetic testing is recommended to confirm the diagnosis. Several deleterious mutations in the HSD3B2 gene have been associated with salt-wasting (SW) crisis in the neonatal period, while missense mutations have been associated with a non-SW phenotype. Boys may have ambiguous genitalia, whereas girls present with mild or no virilization at birth. The existence of non-classic 3βHSD2D is controversial. In an acute SW crisis, the treatment includes prompt rehydration, correction of hypoglycemia, and parenteral hydrocortisone. Similar to other forms of CAH, glucocorticoid and mineralocorticoid replacement is needed for long-term management. In addition, sex hormone replacement therapy may be required if normal progress through puberty is failing. Little is known regarding possible negative long-term consequences of 3βHSD2D and its treatments, e.g., fertility, final height, osteoporosis and fractures, adrenal and testicular tumor risk, and mortality.
Conclusion
Knowledge is mainly based on case reports but many long-term outcomes could be presumed to be similar to other types of CAH, mainly 21-hydroxylase deficiency, although in 3βHSD2D it seems to be more difficult to suppress the androgens.
http://bit.ly/2GnuWXZ
Stepwise approach towards adoption of allergen immunotherapy for allergic rhinitis and asthma patients in daily practice in Belgium: a BelSACI-Abeforcal-EUFOREA statement
Allergic rhinitis (AR) affects 23–30% of the European population with equal prevalence reported in Belgium. Despite guidelines on the correct use of effective treatment, up to 40% of AR patients remain uncontr...
http://bit.ly/2Sur9hO
Using Data Mining Techniques to Examine Domestic Violence Topics on Twitter
Violence and Gender, Ahead of Print.
http://bit.ly/2S9XLOD
Disruption of Cortical Dopaminergic Modulation Impairs Preparatory Activity and Delays Licking Initiation
Abstract
Dysfunction of motor cortices is thought to contribute to motor disorders such as Parkinson's disease (PD). However, little is known on the link between cortical dopaminergic loss, abnormalities in motor cortex neural activity and motor deficits. We address the role of dopamine in modulating motor cortical activity by focusing on the anterior lateral motor cortex (ALM) of mice performing a cued-licking task. We first demonstrate licking deficits and concurrent alterations of spiking activity in ALM of head-fixed mice with unilateral depletion of dopaminergic neurons (i.e., mice injected with 6-OHDA into the medial forebrain bundle). Hemilesioned mice displayed delayed licking initiation, shorter duration of licking bouts, and lateral deviation of tongue protrusions. In parallel with these motor deficits, we observed a reduction in the prevalence of cue responsive neurons and altered preparatory activity. Acute and local blockade of D1 receptors in ALM recapitulated some of the key behavioral and neural deficits observed in hemilesioned mice. Altogether, our data show a direct relationship between cortical D1 receptor modulation, cue-evoked, and preparatory activity in ALM, and licking initiation.http://bit.ly/2WCZ9YC
Early Interactive Acoustic Experience with Non-speech Generalizes to Speech and Confers a Syllabic Processing Advantage at 9 Months
Abstract
During early development, the infant brain is highly plastic and sensory experiences modulate emerging cortical maps, enhancing processing efficiency as infants set up key linguistic precursors. Early interactive acoustic experience (IAE) with spectrotemporally-modulated non-speech has been shown to facilitate optimal acoustic processing and generalizes to novel non-speech sounds at 7-months-of-age. Here we demonstrate that effects of non-speech IAE endure well beyond the immediate training period and robustly generalize to speech processing. Infants who received non-speech IAE differed at 9-months-of-age from both naïve controls and those with only passive acoustic exposure, demonstrating broad modulation of oscillatory dynamics. For the standard syllable, increased high-gamma (>70 Hz) power within auditory cortices indicates that IAE fosters native speech processing, facilitating establishment of phonemic representations. The higher left beta power seen may reflect increased linking of sensory information and corresponding articulatory patterns, while bilateral decreases in theta power suggest more mature automatized speech processing, as less neuronal resources were allocated to process syllabic information. For the deviant syllable, left-lateralized gamma (<70 Hz) enhancement suggests IAE promotes phonemic-related discrimination abilities. Theta power increases in right auditory cortex, known for favoring slow-rate decoding, implies IAE facilitates the more demanding processing of the sporadic deviant syllable.http://bit.ly/2RzRZAN
Histological and MRI Study of the Development of the Human Indusium Griseum
Abstract
To uncover the ontogenesis of the human indusium griseum (IG), 28 post-mortem fetal human brains, 12–40 postconceptional weeks (PCW) of age, and 4 adult brains were analyzed immunohistochemically and compared with post-mortem magnetic resonance imaging (MRI) of 28 fetal brains (14–41 PCW). The morphogenesis of the IG occurred between 12 and 15 PCW, transforming the bilateral IG primordia into a ribbon-like cortical lamina. The histogenetic transition of sub-laminated zones into the three-layered cortical organization occurred between 15 and 35 PCW, concomitantly with rapid cell differentiation that occurred from 18 to 28 PCW and the elaboration of neuronal connectivity during the entire second half of gestation. The increasing number of total cells and neurons in the IG at 25 and 35 PCW confirmed its continued differentiation throughout this period. High-field 3.0 T post-mortem MRI enabled visualization of the IG at the mid-fetal stage using T2-weighted sequences. In conclusion, the IG had a distinct histogenetic differentiation pattern than that of the neighboring intralimbic areas of the same ontogenetic origin, and did not show any signs of regression during the fetal period or postnatally, implying a functional role of the IG in the adult brain, which is yet to be disclosed.http://bit.ly/2WCUGFv
Multimodal Parcellations and Extensive Behavioral Profiling Tackling the Hippocampus Gradient
Abstract
The hippocampus displays a complex organization and function that is perturbed in many neuropathologies. Histological work revealed a complex arrangement of subfields along the medial–lateral and the ventral–dorsal dimension, which contrasts with the anterior–posterior functional differentiation. The variety of maps has raised the need for an integrative multimodal view. We applied connectivity-based parcellation to 1) intrinsic connectivity 2) task-based connectivity, and 3) structural covariance, as complementary windows into structural and functional differentiation of the hippocampus. Strikingly, while functional properties (i.e., intrinsic and task-based) revealed similar partitions dominated by an anterior–posterior organization, structural covariance exhibited a hybrid pattern reflecting both functional and cytoarchitectonic subdivision. Capitalizing on the consistency of functional parcellations, we defined robust functional maps at different levels of partitions, which are openly available for the scientific community. Our functional maps demonstrated a head–body and tail partition, subdivided along the anterior–posterior and medial–lateral axis. Behavioral profiling of these fine partitions based on activation data indicated an emotion–cognition gradient along the anterior–posterior axis and additionally suggested a self-world-centric gradient supporting the role of the hippocampus in the construction of abstract representations for spatial navigation and episodic memory.http://bit.ly/2RE2cMC
The Cortical Neuroimmune Regulator TANK Affects Emotional Processing and Enhances Alcohol Drinking: A Translational Study
Abstract
Alcohol abuse is a major public health problem worldwide. Understanding the molecular mechanisms that control regular drinking may help to reduce hazards of alcohol consumption. While immunological mechanisms have been related to alcohol drinking, most studies reported changes in immune function that are secondary to alcohol use. In this report, we analyse how the gene "TRAF family member-associated NF-κB activator" (TANK) affects alcohol drinking behavior. Based on our recent discovery in a large GWAS dataset that suggested an association of TANK, SNP rs197273, with alcohol drinking, we report that SNP rs197273 in TANK is associated both with gene expression (P = 1.16 × 10−19) and regional methylation (P = 5.90 × 10−25). A tank knock out mouse model suggests a role of TANK in alcohol drinking, anxiety-related behavior, as well as alcohol exposure induced activation of insular cortex NF-κB. Functional and structural neuroimaging studies among up to 1896 adolescents reveal that TANK is involved in the control of brain activity in areas of aversive interoceptive processing, including the insular cortex, but not in areas related to reinforcement, reward processing or impulsiveness. Our findings suggest that the cortical neuroimmune regulator TANK is associated with enhanced aversive emotional processing that better protects from the establishment of alcohol drinking behavior.http://bit.ly/2WIpfts
Mapping Alterations of the Functional Structure of the Cerebral Cortex in Obsessive–Compulsive Disorder
Abstract
We mapped alterations of the functional structure of the cerebral cortex using a novel imaging approach in a sample of 160 obsessive–compulsive disorder (OCD) patients. Whole-brain functional connectivity maps were generated using multidistance measures of intracortical neural activity coupling defined within isodistant local areas. OCD patients demonstrated neural activity desynchronization within the orbitofrontal cortex and in primary somatosensory, auditory, visual, gustatory, and olfactory areas. Symptom severity was significantly associated with the degree of functional structure alteration in OCD-relevant brain regions. By means of a novel imaging perspective, we once again identified brain alterations in the orbitofrontal cortex, involving areas purportedly implicated in the pathophysiology of OCD. However, our results also indicated that weaker intracortical activity coupling is also present in each primary sensory area. On the basis of previous neurophysiological studies, such cortical activity desynchronization may best be interpreted as reflecting deficient inhibitory neuron activity and altered sensory filtering.http://bit.ly/2RE2vqy
The Subplate: A Potential Driver of Cortical Folding?
Abstract
In many species of Mammalia, the surface of the brain develops from a smooth structure to one with many fissures and folds, allowing for vast expansion of the surface area of the cortex. The importance of understanding what drives cortical folding extends beyond mere curiosity, as conditions such as preterm birth, intrauterine growth restriction, and fetal alcohol syndrome are associated with impaired folding in the infant and child. Despite being a key feature of brain development, the mechanisms driving cortical folding remain largely unknown. In this review we discuss the possible role of the subplate, a developmentally transient compartment, in directing region-dependent development leading to sulcal and gyral formation. We discuss the development of the subplate in species with lissencephalic and gyrencephalic cortices, the characteristics of the cells found in the subplate, and the possible presence of molecular cues that guide axons into, and out of, the overlying and multilayered cortex before the appearance of definitive cortical folds. An understanding of what drives cortical folding is likely to help in understanding the origins of abnormal folding patterns in clinical pathologies.http://bit.ly/2WJbWZo
Treatment of oral cancers during pregnancy: a case-based discussion
Malignancies occur in approximately 1:1000 pregnancies; the most common being breast (46%) and hematological (18%) malignancies. Oral cancers account for only 2% of all cancers in pregnant women, and there are...
http://bit.ly/2UGyacY
Pressure induced tissue resection in the larynx: A preliminary canine study
Objectives
The application of laser (light amplification by stimulated emission of radiation) energy in the larynx relies on thermal injury. The impact of this injury on adjacent tissue can be undesirable. Attempts have been made to limit the extent and range of injury to adjacent tissue. The O‐Pel Surgical System (Precise Light Surgical, Inc., Campbell, CA), a new technology, utilizes kinetic energy through Pressure Induced Tissue Resection (PITR) (Precise Light Surgical, Inc.) to cut tissue, theoretically eliminating injury to adjacent tissue. The purpose of this study was to evaluate the PSL in canine vocal folds.
Methods
Four dogs underwent PITR incisions (4 mJ pulses at 200 Hz) on their vocal folds, through mucosa into the muscle. The animals were sacrificed at days 0, 3, 7, and 21 days postsurgery. The larynges were harvested and histology was performed with hematoxylin and eosin, Masson trichrome, and Verhoeff‐van Gieson.
Results
At day 0, focal denudation of the epithelium and coagulation necrosis in the lamina propria and adjacent connective tissue are noted. On days 3 and 7, an inflammatory infiltrate of neutrophils is seen within the lamina propria and surrounding connective tissue with minimal edema and early deposition of collagen. At day 21, the mucosa is completely regenerated with the area of previous PITR into the muscle replaced with thick bundles of collagen.
Conclusion
The unique PITR characteristics offer a potentially unique cutting technology for laryngeal microsurgery. The current canine study suggests appropriate and rapid healing. With refinements of the tip size of the probe and adjustment of energy, PITR will likely be an appropriate alternate to traditional lasers in laryngeal surgery.
Level of Evidence
NA. Laryngoscope, 2019
http://bit.ly/2SsWMZg
Toripalimab or Placebo With Paclitaxel and Cisplatin in Esophageal Squamous Cell Carcinoma
Condition: Advanced or Metastatic Esophageal Squamous Cell Cancer Without Previous Systemic Chemotherapy
Intervention: Biological: JS001
Sponsor: Shanghai Junshi Bioscience Co., Ltd.
Recruiting
http://bit.ly/2I3HMx5
Intervention: Biological: JS001
Sponsor: Shanghai Junshi Bioscience Co., Ltd.
Recruiting
http://bit.ly/2I3HMx5
TreatmENT of AnastomotiC Leakage After Esophagectomy
Conditions: Esophageal Cancer; Esophageal Neoplasms
Intervention: Other: Intervantions for anastomotic leakage after esophagectomy
Sponsors: Radboud University; Dutch Upper-GI Cancer Audit group (DUCA); Oesophago-Gastric Anastomosis Audit (OGAA)
Not yet recruiting
http://bit.ly/2t5qNQw
Intervention: Other: Intervantions for anastomotic leakage after esophagectomy
Sponsors: Radboud University; Dutch Upper-GI Cancer Audit group (DUCA); Oesophago-Gastric Anastomosis Audit (OGAA)
Not yet recruiting
http://bit.ly/2t5qNQw
Radiotherapy, Carboplatin/Paclitaxel and Nivolumab for High Risk HPV-related Head and Neck Cancer
Condition: Oropharynx Squamous Cell Carcinoma
Interventions: Drug: Nivolumab; Drug: Carboplatin; Drug: Paclitaxel; Radiation: Radiation Therapy
Sponsors: University of Michigan Rogel Cancer Center; Bristol-Myers Squibb
Not yet recruiting
http://bit.ly/2HPI6iB
Interventions: Drug: Nivolumab; Drug: Carboplatin; Drug: Paclitaxel; Radiation: Radiation Therapy
Sponsors: University of Michigan Rogel Cancer Center; Bristol-Myers Squibb
Not yet recruiting
http://bit.ly/2HPI6iB
TPST-1120 as Monotherapy and in Combination With (Nivolumab, Docetaxel or Cetuximab) in Subjects With Advanced Cancers
Conditions: Hepatocellular Carcinoma; Metastatic Castration Resistant Prostate Cancer; Renal Cell Carcinoma; Non-small Cell Lung Cancer; Colorectal Cancer; Squamous Cell Carcinoma of Head and Neck; Triple-Negative Breast Cancer; Urothelial Carcinoma; Cholangiocarcinoma; GastroEsophageal Cancer; Pancreatic Cancer; Sarcoma
Interventions: Drug: Part 1 TPST-1120; Drug: Part 2a TPST-1120 + nivolumab; Drug: Part 2b TPST-1120 + docetaxel; Drug: Part 2c TPST-1120 + cetuximab; Drug: Part 3 TPST-1120; Drug: Part 4a TPST-1120 + nivolumab; Drug: Part 4b TPST-1120 + docetaxel; Drug: Part 4c TPST-1120 + cetuximab
Sponsor: Tempest Therapeutics
Not yet recruiting
http://bit.ly/2G8dbMR
Interventions: Drug: Part 1 TPST-1120; Drug: Part 2a TPST-1120 + nivolumab; Drug: Part 2b TPST-1120 + docetaxel; Drug: Part 2c TPST-1120 + cetuximab; Drug: Part 3 TPST-1120; Drug: Part 4a TPST-1120 + nivolumab; Drug: Part 4b TPST-1120 + docetaxel; Drug: Part 4c TPST-1120 + cetuximab
Sponsor: Tempest Therapeutics
Not yet recruiting
http://bit.ly/2G8dbMR
Safety and Efficacy of KY1044 and Atezolizumab in Advanced Cancer
Conditions: Squamous Cell Carcinoma of Head and Neck; Non-small Cell Lung Cancer; Hepatocellular Carcinoma; Esophageal Cancer; Gastric Cancer; Melanoma; Renal Cell Carcinoma; Pancreatic Cancer; Cervical Cancer; Triple Negative Breast Cancer; Advanced Cancer
Interventions: Drug: KY1044; Drug: KY1044 and atezolizumab
Sponsor: Kymab Limited
Recruiting
http://bit.ly/2D7Dm2g
Interventions: Drug: KY1044; Drug: KY1044 and atezolizumab
Sponsor: Kymab Limited
Recruiting
http://bit.ly/2D7Dm2g
Photon Therapy Versus Proton Therapy in Early Tonsil Cancer.
Condition: Tonsil Cancer
Intervention: Radiation: Radiotherapy
Sponsor: Lund University Hospital
Recruiting
http://bit.ly/2GeoFi7
Intervention: Radiation: Radiotherapy
Sponsor: Lund University Hospital
Recruiting
http://bit.ly/2GeoFi7
PD-L1 ImagiNg to prediCt Durvalumab Treatment Response in HNSCC
Condition: Head and Neck Cancer
Interventions: Diagnostic Test: PD-L1 imaging; Drug: Durvalumab
Sponsors: Radboud University; AstraZeneca
Not yet recruiting
http://bit.ly/2D9Ywwy
Interventions: Diagnostic Test: PD-L1 imaging; Drug: Durvalumab
Sponsors: Radboud University; AstraZeneca
Not yet recruiting
http://bit.ly/2D9Ywwy
Toripalimab or Placebo With Paclitaxel and Cisplatin in Esophageal Squamous Cell Carcinoma
Condition: Advanced or Metastatic Esophageal Squamous Cell Cancer Without Previous Systemic Chemotherapy
Intervention: Biological: JS001
Sponsor: Shanghai Junshi Bioscience Co., Ltd.
Recruiting
http://bit.ly/2I3HMx5
Intervention: Biological: JS001
Sponsor: Shanghai Junshi Bioscience Co., Ltd.
Recruiting
http://bit.ly/2I3HMx5
TreatmENT of AnastomotiC Leakage After Esophagectomy
Conditions: Esophageal Cancer; Esophageal Neoplasms
Intervention: Other: Intervantions for anastomotic leakage after esophagectomy
Sponsors: Radboud University; Dutch Upper-GI Cancer Audit group (DUCA); Oesophago-Gastric Anastomosis Audit (OGAA)
Not yet recruiting
http://bit.ly/2t5qNQw
Intervention: Other: Intervantions for anastomotic leakage after esophagectomy
Sponsors: Radboud University; Dutch Upper-GI Cancer Audit group (DUCA); Oesophago-Gastric Anastomosis Audit (OGAA)
Not yet recruiting
http://bit.ly/2t5qNQw
Radiotherapy, Carboplatin/Paclitaxel and Nivolumab for High Risk HPV-related Head and Neck Cancer
Condition: Oropharynx Squamous Cell Carcinoma
Interventions: Drug: Nivolumab; Drug: Carboplatin; Drug: Paclitaxel; Radiation: Radiation Therapy
Sponsors: University of Michigan Rogel Cancer Center; Bristol-Myers Squibb
Not yet recruiting
http://bit.ly/2HPI6iB
Interventions: Drug: Nivolumab; Drug: Carboplatin; Drug: Paclitaxel; Radiation: Radiation Therapy
Sponsors: University of Michigan Rogel Cancer Center; Bristol-Myers Squibb
Not yet recruiting
http://bit.ly/2HPI6iB
TPST-1120 as Monotherapy and in Combination With (Nivolumab, Docetaxel or Cetuximab) in Subjects With Advanced Cancers
Conditions: Hepatocellular Carcinoma; Metastatic Castration Resistant Prostate Cancer; Renal Cell Carcinoma; Non-small Cell Lung Cancer; Colorectal Cancer; Squamous Cell Carcinoma of Head and Neck; Triple-Negative Breast Cancer; Urothelial Carcinoma; Cholangiocarcinoma; GastroEsophageal Cancer; Pancreatic Cancer; Sarcoma
Interventions: Drug: Part 1 TPST-1120; Drug: Part 2a TPST-1120 + nivolumab; Drug: Part 2b TPST-1120 + docetaxel; Drug: Part 2c TPST-1120 + cetuximab; Drug: Part 3 TPST-1120; Drug: Part 4a TPST-1120 + nivolumab; Drug: Part 4b TPST-1120 + docetaxel; Drug: Part 4c TPST-1120 + cetuximab
Sponsor: Tempest Therapeutics
Not yet recruiting
http://bit.ly/2G8dbMR
Interventions: Drug: Part 1 TPST-1120; Drug: Part 2a TPST-1120 + nivolumab; Drug: Part 2b TPST-1120 + docetaxel; Drug: Part 2c TPST-1120 + cetuximab; Drug: Part 3 TPST-1120; Drug: Part 4a TPST-1120 + nivolumab; Drug: Part 4b TPST-1120 + docetaxel; Drug: Part 4c TPST-1120 + cetuximab
Sponsor: Tempest Therapeutics
Not yet recruiting
http://bit.ly/2G8dbMR
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