Atovaquone oral bioavailability enhancement using electrospraying technology

Publication date: 1 January 2018
Source:European Journal of Pharmaceutical Sciences, Volume 111
Author(s): Aditya Darade, Sulabha Pathak, Shobhona Sharma, Vandana Patravale
Atovaquone in combination with proguanil hydrochloride, marketed as Malarone® tablets by GlaxoSmithKline (GSK), is prescribed for the treatment of malaria. High dose and poor bioavailability are the main hurdles associated with atovaquone oral therapy. The present study reports development of atovaquone nanoparticles, using in house designed and fabricated electrospraying equipment, and the assessment of bioavailability and therapeutic efficacy of the nanoparticles after oral administration. Solid nanoparticles of atovaquone were successfully produced by electrospraying and were characterized for particle size and flow properties. Differential Scanning Calorimetry, X-ray Diffraction, Fourier Transform Infrared Spectroscopy studies were also carried out. Atovaquone nanoparticles along with proguanil hydrochloride and a suitable wetting agent were filled in size 2 hard gelatin capsules. The formulation was compared with Malarone® tablets (GSK) and Mepron® suspension (GSK) in terms of in vitro release profile and in vivo pharmacokinetic studies. It showed 2.9-fold and 1.8-fold improved bioavailability in rats compared to Malarone® tablets and Mepron® suspension respectively. Therapeutic efficacy of the formulation was determined using modified Peter's 4-day suppressive tests and clinical simulation studies using Plasmodium berghei ANKA infected Swiss mice and compared to Malarone®. The developed formulation showed a 128-fold dose reduction in the modified Peter's 4-day suppressive tests and 32-fold dose reduction in clinical simulation studies. Given that only one capsule a day of developed formulation is required to be administered orally compared to 4 Malarone® tablets once a day and that too at a significantly reduced dose, this nanoparticle formulation will definitely reduce the side-effects of the treatment and is also likely to increase patient compliance.

Graphical abstract

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Improvement in the water solubility of drugs with a solid dispersion system by spray drying and hot-melt extrusion with using the amphiphilic polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer and d-mannitol

Publication date: 1 January 2018
Source:European Journal of Pharmaceutical Sciences, Volume 111
Author(s): Noriko Ogawa, Tomoki Hiramatsu, Ryohei Suzuki, Ryohei Okamoto, Kohei Shibagaki, Kosuke Fujita, Chisato Takahashi, Yoshiaki Kawashima, Hiromitsu Yamamoto
The aim of this study was to prepare and characterize solid dispersion particles with a novel amphiphilic polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, as a water-soluble carrier. Solid dispersion particles were prepared by hot-melt extrusion and spray drying. Indomethacin (IMC) was used as a model comprising drugs with low solubility in water and d-mannitol (MAN) was used as an excipient. The physicochemical properties of prepared particles were characterized by scanning electron microscopy, thermal analysis, powder X-ray diffraction (PXRD) analysis, FTIR spectra analysis, and drug release studies. Stability studies were also conducted under stress conditions at 40°C, 75% relative humidity. We found that dissolution behavior of the original drug crystal could be improved by solid dispersion with the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer. The PXRD pattern and thermal analysis indicated that the solid dispersion prepared with the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer and IMC was in an amorphous state. FTIR spectra analysis indicated that the interaction manner between the polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer and IMC may differ with the preparation method and formulation of solid dispersions. Stability studies proved that the amorphous state of IMC in solid dispersion particles was preserved under stress conditions for more than two weeks.

Graphical abstract

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Peristomal psoriasis: an intriguing new subset of psoriasis

http://ift.tt/2xvFImD

Delusional infestation caused by pramipexole

http://ift.tt/2xuiLW3

Efficacy of perilesional and intralesional triamcinolone acetonide injections in pemphigus vulgaris lesions of the scalp: an effective therapeutic option

Summary

The scalp is a common location for pemphigus vulgaris (PV), and scalp lesions may be resistant to standard treatment. Perilesional/intralesional triamcinolone acetonide (TA) injections have been used successfully to treat oropharyngeal and ocular involvement in PV. Data on the efficacy of perilesional and intralesional triamcinolone acetonide injections in scalp lesions in PV are lacking. We report two patients with immunopathologically and histopathologically confirmed PV and residual scalp lesions resistant to standard treatment, who were treated with perilesional and intralesional injections of TA 10 mg/mL. Clearance of scalp lesions was achieved after one after, respectively, one and two perilesional and intralesional injections. Perilesional and intralesional TA injections may serve as an effective and safe treatment for recalcitrant scalp lesions in pemphigus.

http://ift.tt/2xvIeta

First-line treatment in lymphomatoid papulosis: a retrospective multicentre study

Summary

Background

Data regarding response to treatment in lymphomatoid papulosis (LyP) are scarce.

Aim

To assess the daily clinical practice approach to LyP and the response to first-line treatments.

Methods

This was a retrospective study enrolling 252 patients with LyP.

Results

Topical steroids, methotrexate and phototherapy were the most common first-line treatments, prescribed for 35%, 20% and 14% of the patients, respectively. Complete response (CR) was achieved in 48% of treated patients. Eczematous lesions significantly increased relative risk (RR) of not achieving CR (RR = 1.76; 95% CI 1.16–2.11). Overall median time to CR was 10 months (95% CI 6–13 months), and 78% of complete responders showed cutaneous relapse; both results were similar for all treatment groups (P > 0.05). Overall estimated median disease-free survival (DFS) was 11 months (95% CI 9–13 months) but DFS for patients treated with phototherapy was 23 months (95% CI 10–36 months; P < 0.03). Having the Type A LyP variant (RR = 2.04; 95% CI 0.96–4.30) and receiving a first-line treatment other than phototherapy (RR = 5.33; 95% CI 0.84–33.89) were significantly associated with cutaneous early relapse. Of the 252 patients, 31 (13%) had associated mycosis fungoides unrelated to therapeutic approach, type of LyP or T-cell receptor clonality.

Conclusions

Current epidemiological, clinical and pathological data support previous results. Topical steroids, phototherapy and methotrexate are the most frequently prescribed first-line treatments. Although CR and cutaneous relapse rates do not differ between them, phototherapy achieves a longer DFS. Presence of Type A LyP and use of topical steroid or methotrexate were associated with an increased risk of early relapse.

http://ift.tt/2xulMWr

Self-reported minor infections in patients with hidradenitis suppurativa and healthy controls

Summary

Background

Patients with hidradenitis suppurativa (HS) often report opportunistic infections such as herpes and urinary tract infections.

Aim

To compare opportunistic infections in patients with HS against a group of healthy controls (HCs).

Methods

In total, 99 patients with HS and 109 HCs were recruited at random to this retrospective case–control study. We devised a questionnaire to explore the frequency of minor infections, general practitioner (GP) visits and sick days experienced during the past 6 months. Additionally, participants were asked if they felt unwell more often compared with their peers.

Results

Patients with HS felt unwell more often than did HCs (26.3% vs. 7.3%, P < 0.001). Although there was no difference between the groups in five of the seven diseases studied, patients with HS had a higher frequency of the common cold (P < 0.01) and genital herpes (P < 0.01). Number of pack-years of smoking did not affect risk of infections (Pearson correlation, P = 0.51). Subgroup analysis of nonsmokers found the same differences in frequency of minor infections, common cold and genital herpes between patients with HS and controls.

Conclusions

Patients with HS appear to experience more frequently symptoms compatible with minor infections in general, and the common cold and genital herpes specifically. This results in more GP visits and more sick days. Further research is needed to determine if this is caused by an immunological hyper-reactive state in these patients or a reduced threshold for minor infections.

http://ift.tt/2xvGfoS

Eruptive melanocytic naevi secondary to azathioprine: case report and review of the literature

http://ift.tt/2xuAL2k

Ultraviolet filters in hair-care products: a possible link with frontal fibrosing alopecia and lichen planopilaris

http://ift.tt/2xvXkie

Peristomal psoriasis: an intriguing new subset of psoriasis

http://ift.tt/2xvFImD

Delusional infestation caused by pramipexole

http://ift.tt/2xuiLW3

Efficacy of perilesional and intralesional triamcinolone acetonide injections in pemphigus vulgaris lesions of the scalp: an effective therapeutic option

Summary

The scalp is a common location for pemphigus vulgaris (PV), and scalp lesions may be resistant to standard treatment. Perilesional/intralesional triamcinolone acetonide (TA) injections have been used successfully to treat oropharyngeal and ocular involvement in PV. Data on the efficacy of perilesional and intralesional triamcinolone acetonide injections in scalp lesions in PV are lacking. We report two patients with immunopathologically and histopathologically confirmed PV and residual scalp lesions resistant to standard treatment, who were treated with perilesional and intralesional injections of TA 10 mg/mL. Clearance of scalp lesions was achieved after one after, respectively, one and two perilesional and intralesional injections. Perilesional and intralesional TA injections may serve as an effective and safe treatment for recalcitrant scalp lesions in pemphigus.

http://ift.tt/2xvIeta

First-line treatment in lymphomatoid papulosis: a retrospective multicentre study

Summary

Background

Data regarding response to treatment in lymphomatoid papulosis (LyP) are scarce.

Aim

To assess the daily clinical practice approach to LyP and the response to first-line treatments.

Methods

This was a retrospective study enrolling 252 patients with LyP.

Results

Topical steroids, methotrexate and phototherapy were the most common first-line treatments, prescribed for 35%, 20% and 14% of the patients, respectively. Complete response (CR) was achieved in 48% of treated patients. Eczematous lesions significantly increased relative risk (RR) of not achieving CR (RR = 1.76; 95% CI 1.16–2.11). Overall median time to CR was 10 months (95% CI 6–13 months), and 78% of complete responders showed cutaneous relapse; both results were similar for all treatment groups (P > 0.05). Overall estimated median disease-free survival (DFS) was 11 months (95% CI 9–13 months) but DFS for patients treated with phototherapy was 23 months (95% CI 10–36 months; P < 0.03). Having the Type A LyP variant (RR = 2.04; 95% CI 0.96–4.30) and receiving a first-line treatment other than phototherapy (RR = 5.33; 95% CI 0.84–33.89) were significantly associated with cutaneous early relapse. Of the 252 patients, 31 (13%) had associated mycosis fungoides unrelated to therapeutic approach, type of LyP or T-cell receptor clonality.

Conclusions

Current epidemiological, clinical and pathological data support previous results. Topical steroids, phototherapy and methotrexate are the most frequently prescribed first-line treatments. Although CR and cutaneous relapse rates do not differ between them, phototherapy achieves a longer DFS. Presence of Type A LyP and use of topical steroid or methotrexate were associated with an increased risk of early relapse.

http://ift.tt/2xulMWr

Self-reported minor infections in patients with hidradenitis suppurativa and healthy controls

Summary

Background

Patients with hidradenitis suppurativa (HS) often report opportunistic infections such as herpes and urinary tract infections.

Aim

To compare opportunistic infections in patients with HS against a group of healthy controls (HCs).

Methods

In total, 99 patients with HS and 109 HCs were recruited at random to this retrospective case–control study. We devised a questionnaire to explore the frequency of minor infections, general practitioner (GP) visits and sick days experienced during the past 6 months. Additionally, participants were asked if they felt unwell more often compared with their peers.

Results

Patients with HS felt unwell more often than did HCs (26.3% vs. 7.3%, P < 0.001). Although there was no difference between the groups in five of the seven diseases studied, patients with HS had a higher frequency of the common cold (P < 0.01) and genital herpes (P < 0.01). Number of pack-years of smoking did not affect risk of infections (Pearson correlation, P = 0.51). Subgroup analysis of nonsmokers found the same differences in frequency of minor infections, common cold and genital herpes between patients with HS and controls.

Conclusions

Patients with HS appear to experience more frequently symptoms compatible with minor infections in general, and the common cold and genital herpes specifically. This results in more GP visits and more sick days. Further research is needed to determine if this is caused by an immunological hyper-reactive state in these patients or a reduced threshold for minor infections.

http://ift.tt/2xvGfoS

Eruptive melanocytic naevi secondary to azathioprine: case report and review of the literature

http://ift.tt/2xuAL2k

Ultraviolet filters in hair-care products: a possible link with frontal fibrosing alopecia and lichen planopilaris

http://ift.tt/2xvXkie

Mapping the Landscape of Patient-Centric Activities Within Clinical Research

Publication date: Available online 9 October 2017
Source:Clinical Therapeutics
Author(s): Mary Jo Lamberti, Josephine Awatin
PurposeAlthough there has been more involvement by patients in the drug-development process, there are not a lot of published data that quantify patient-centric activities or that document these activities across a large scale. In order to examine the patient-centricity landscape and to quantify the adoption and implementation of these initiatives, the Tufts Center for the Study of Drug Development and the Drug Information Association collaborated on a research study. The study examined patient-centric activities implemented by pharmaceutical, biotechnology, and contract research organizations, as well as activities being piloted or in the planning stages.MethodsA global industry survey was conducted across pharmaceutical, biotechnology, and contract research organizations, assessing 25 patient-centric activities within clinical research. Some of these initiatives involve the use of social media to engage with patients, or the use of social listening to monitor study activity. Initiatives being implemented, planned, or piloted in addition to those not being considered were evaluated by respondents. Twenty-two unique companies responded to the survey, representing a mix of large, mid-sized, and small organizations.FindingsThe most widely adopted patient-centric initiatives, including activities both implemented and piloted across organizations, were patient advisory boards (17/22 companies), professional panels (16), lay-language clinical trial results summaries (13), assessment of the patient–organization landscape (10), and the use of home nursing networks (9).ImplicationsThe results of the study suggest that organizations have a varied approach to the adoption and implementation of patient-centric initiatives, with more activities occurring in the planning stages than are being piloted or implemented. Many factors affect implementation and adoption, including buy-in by senior management, organizational vision, resources, and level of investment.



http://ift.tt/2ycOBFn

Impact of Penicillin Allergy on Time to First Dose of Antimicrobial Therapy and Clinical Outcomes

Publication date: Available online 9 October 2017
Source:Clinical Therapeutics
Author(s): Erin L. Conway, Ken Lin, John A. Sellick, Kari Kurtzhalts, James Carbo, Michael C. Ott, Kari A. Mergenhagen
PurposeThe objective of this study was to evaluate the impact of a listed penicillin allergy on the time to first dose of antibiotic in a Veterans Affairs hospital. Additional clinical outcomes of patients with penicillin allergies were compared with those of patients without a penicillin allergy.MethodsA retrospective chart review of veterans admitted through the emergency department with a diagnosis of pneumonia, urinary tract infection, bacteremia, and sepsis from January 2006 to December 2015 was conducted. The primary outcome was time to first dose of antibiotic treatment, defined as the time from when the patient presented to the emergency department to the medication administration time. Secondary outcomes included total antibiotic therapy duration and treatment outcomes, including mortality, length of stay, and 30-day readmission rate.FindingsA total of 403 patients were included in the final analysis; 57 patients (14.1%) had a listed penicillin allergy. The average age of the population was 75 years and 99% of the population was male. The mean time to first dose of antibiotic treatment for patients with a penicillin allergy was prolonged compared with those without a penicillin allergy (236.1 vs 186.6 minutes; P = 0.03), resulting in an approximately 50-minute delay. Penicillin-allergic patients were more likely to receive a carbapenem or fluoroquinolone antibiotic (P < 0.0001).ImplicationsPatients with a penicillin allergy had a prolonged time to first dose of antibiotic therapy. No significant differences were found in total antibiotic duration, length of stay, or 30-day readmission rate. The small sample size, older population, and single-center nature of this study may limit the generalizability of the present findings to other populations.



http://ift.tt/2y5r4an

miRNA Genetic Variants: as Potential Diagnostic Biomarkers For Oral Cancer

Publication date: Available online 10 October 2017
Source:Pathology - Research and Practice
Author(s): Divya Tandon, Jayant Dewangan, Sonal Srivastava, Vivek Kumar Garg, Srikanta Kumar Rath
MicroRNAs (miRNAs) comprise a novel class of small, non-coding endogenous RNAs that have a role in the plethora of regulatory activities by directing their target mRNAs for degradation or translational repression. Single nucleotide polymorphisms (SNPs) in miRNA genes can lead to alteration in mRNA expression, resulting in serious consequences. Detection of miRNA-polymorphisms can potentially improve diagnosis, treatment, prognosis in patients and has extreme implications in the fields of pharmacogenomics and personalization of medicine. The aim of this study is to investigate the association between miR-499 A/G and miR-149 C/T polymorphisms with susceptibility to development of Oral Squamous Cell Carcinoma (OSCC). 200 histopathologically diagnosed and confirmed samples from OSCC patients and 200 control samples from the general population were recruited for the study. All OSCC patients were graded based on their differentiation, and genetic analysis was performed by PCR-RFLP and sequencing. qRT-PCR was carried out to compare the expression of miR-499 and miR-149 in different grades of various stages of OSCC patients concerning to the controls. Further Immunohistochemistry (IHC) was performed to study the target gene of miR-499. The study shows a probable association of miR-499 A/G and miR-149 C/T with susceptibility of OSCC. Random sequencing analysis and Immunohistochemistry contribute to the result that miR-499 A/G increases the susceptibility of OSCC by targeting SOX-6. PCR- Restriction Fragment Length Polymorphism (RFLP) and multivariable logistic analysis revealed that there is a significant association between miR-149 CT+TT and CT and susceptibility of OSCC. Our study suggests that miR-499 A/G and miR-149 C/T polymorphisms may play crucial roles in susceptibility and development of OSCC in Indian population.



http://ift.tt/2xvDBiR

DNMT1 is associated with cell cycle and DNA replication gene sets in diffuse large B-cell lymphoma

Publication date: Available online 9 October 2017
Source:Pathology - Research and Practice
Author(s): Suet Kee Loo, Suzina Sheikh Ab. Hamid, Mustaffa Musa, Kah Keng Wong
Dysregulation of DNA (cytosine-5)-methyltransferase 1 (DNMT1) is associated with the pathogenesis of various types of cancer. It has been previously shown that DNMT1 is frequently expressed in diffuse large B-cell lymphoma (DLBCL), however its functions remain to be elucidated in the disease. In this study, we gene expression profiled (GEP) shDNMT1-treated germinal center B-cell-like DLBCL (GCB-DLBCL)-derived cell line (i.e. HT) compared with non-silencing shRNA (control shRNA)-treated HT cells. Independent gene set enrichment analysis (GSEA) performed using GEPs of shRNA-treated HT cells and primary GCB-DLBCL cases derived from two publicly-available datasets (i.e. GSE10846 and GSE31312) produced three separate lists of enriched gene sets for each gene sets collection from Molecular Signatures Database (MSigDB). Subsequent Venn analysis identified 268, 145 and six consensus gene sets from analyzing gene sets in C2 collection (curated gene sets), C5 sub-collection [gene sets from gene ontology (GO) biological process ontology] and Hallmark collection, respectively to be enriched in positive correlation with DNMT1 expression profiles in shRNA-treated HT cells, GSE10846 and GSE31312 datasets [false discovery rate (FDR)<0.05]. Cell cycle progression and DNA replication were among the significantly enriched biological processes (FDR<0.05). Expression of genes involved in the activation of cell cycle and DNA replication (e.g. CDK1, CCNA2, E2F2, PCNA, RFC5 and POLD3) were highly correlated (r>0.8) with DNMT1 expression and significantly downregulated (log fold-change <−1.35; p<0.05) following DNMT1 silencing in HT cells. These results suggest the involvement of DNMT1 in the activation of cell cycle and DNA replication in DLBCL cells.



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Combined Detection of Insulin-Like Growth Factor-Binding Protein 7 Promoter Methylation Improves the Diagnostic Efficacy of AFP in Hepatitis B Virus-associated Hepatocellular Carcinoma

Publication date: Available online 9 October 2017
Source:Pathology - Research and Practice
Author(s): Li-Ping Tao, Xiao-Peng Fan, Yu-Chen Fan, Jing Zhao, Shuai Gao, Kai Wang
This study quantitatively assessed serum insulin-like growth factor-binding protein 7 (IGFBP7) promoter methylation in hepatocellular carcinoma (HCC), and explored its clinical value. A total of 80 patients with hepatitis B virus-associated HCC, 35 patients with chronic hepatitis B (CHB), and 20 healthy controls (HC) were enrolled. MethyLight was used to quantitatively assess the methylation levels of serum IGFBP7 promoter. A logistic regression model was established for the combined evaluation of AFP and serum IGFBP7 promoter methylation. The results showed that mean methylation levels of serum IGFBP7 promoter were significantly higher in HCC (5.33%, interquartile range [IQR] 1.14–15.70%) patients than in individuals with CHB (1.54%, IQR 0.64–2.45%; P<0.01) and HC (0.63%, IQR 0.22–0.98%; P<0.01). In HCC subgroups, patients with vascular invasion, tumor size >3cm and advanced tumor node metastasis (TNM) showed higher methylation levels compared with the remaining groups (P<0.05). Compared with AFP alone, combined determination based on logistic regression analysis significantly improved the area under the receiver operating characteristic (ROC) curve (AUC) (0.759 vs 0.623, P<0.05). In addition, the Youden index was increased from 5.71%, 11.25% and 15.18%, when considering AFP alone at cut-off values of 20, 200, and 400ng/mL, respectively, to 45.71% with IGFBP7 promoter methylation taken into consideration (all P<0.05). These results suggested that combined quantitative measurement of serum IGFBP7 promoter methylation could enhance the diagnostic ability of AFP in distinguishing hepatitis B virus-associated HCC from CHB.



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PATHOBIOLOGY OF HER 2 POSITIVE SMALL INVASIVE (T1a,b) BREAST CANCER: A WOLF IN SHEEP'S CLOTHING

Publication date: Available online 9 October 2017
Source:Pathology - Research and Practice
Author(s): Joško Bezić, Ivana Šamija Projić, Petar Projić, Kristina Meljanac Salopek, Piero Marin Živković, Joško Božić, Snježana Tomić
Small invasive breast cancers (cancers with maximum diameter <1cm, T1a,b) become more prevalent form of breast cancer as a result of the introduction of breast cancer mammographic screening programs. Although associated with an excellent prognosis, T1a,b breast cancers are heterogeneous group of tumors with prognostically unfavorable subset of cases, primarily those with axillary lymph node metastases. To determine if the HER2 overexpression is associated with the prognostically unfavorable traditional clinicopathological features in this group of breast cancers, clinicopathological features (age, tumor size, histological type, histological grade, nodal status, hormone receptor status, proliferation index, lymphovascular invasion, ploidy) of 38 HER2 positive T1a,b cancers were compared with those of the control group consisting of 315 HER2 negative T1a,b cancers. The comparison of clinicopathological features was made using χ² and t-test. HER2 positive T1a,b breast cancers were significantly associated with higher tumor grades (p<0.001), negative hormone receptors (p=0.008), presence of lymphovascular invasion (p=0.025), high proliferation index (p<0.001), and abnormal DNA content (p=0.04). We also noticed the higher frequency of lymph node positive cases in the HER2 positive group of cancers (p=0.05). There were no differences in age, tumor size and histological type between investigated groups. Our group of HER2 positive T1a,b breast cancers was associated with many unfavorable traditional prognostic factors, demonstrating that this subtype of early breast cancer has an aggressive biological phenotype which may have potential benefit from adjuvant chemo and immunotherapy.



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The correlation between XIAP gene polymorphisms and esophageal squamous cell carcinoma susceptibility and prognosis in a Chinese population

Publication date: Available online 9 October 2017
Source:Pathology - Research and Practice
Author(s): Hai Peng, Li-Guo Wang, Xue-Zhi Wang, Ai-Jun Liu
ObjectiveThis study aims to explore the correlation between X-linked inhibitor of apoptosis protein (XIAP) gene polymorphisms (rs8371 and rs9856) with the susceptibility and prognosis of esophageal squamous cell carcinoma (ESCC), providing a potential treatment for ESCC.MethodA total of 170 ESCC patients (case group) and 191 healthy people (control group) were enrolled in our study. Genotyping was conducted on the basis of the ligase detection reaction (LDR). The expressions of XIAP polymorphisms were detected. The patients were followed up every three months until death or the last follow-up day. The overall survival (OS) and progression free survival (PFS) were recorded by Kaplan-Meier survival curve, and the relationship between XIAP gene polymorphism and risk and prognosis of ESCC was assessed by Cox multivariate analysis.ResultTT+CT genotype and T allele frequencies of XIAP rs8371 and rs9856 in the case group were significantly lower compared to those of the control group (all P<0.05), suggesting that TT+CT genotype of XIAP rs8371 and rs9856 was associated with ESCC susceptibility. XIAP rs8371 and rs9856 polymorphisms were associated with tumor node metastasis (TNM) staging, depth of invasion and lymph node metastasis. The OS and PFS of TT+CT genotype carriers of rs8371 were longer than those of CC genotype carriers. Smoking, alcohol, TNM staging, depth of invasion, and lymph node metastasis were significantly associated with the OS and PFS in ESCC patients. Higher TNM staging, depth of invasion, and presence of lymph node metastasis were independent risk factors, while XIAP rs8371 was an independent protective factor for the prognosis of ESCC patients.ConclusionThe present study demonstrates that XIAP rs8371 and rs9856 are associated with susceptibility to ESCC, and rs8371 polymorphisms might serve as an indicator for improved clinical efficacy and prognosis of ESCC patients.



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Comparative Assessment of three Methods to Analyze MGMT Methylation Status in a Series of 350 Gliomas and Gangliogliomas

Publication date: Available online 10 October 2017
Source:Pathology - Research and Practice
Author(s): Leiming Wang, Zhuo Li, Cuicui Liu, Li Chen, Li Liu, Zeliang Hu, Lihong Zhao, Dehong Lu, Lianghong Teng
MGMT promoter methylation is considered as a prognostic and predictive biomarker indicating response to chemotherapy and radiotherapy in glioblastoma. A number of different methods and platforms including pyrosequencing (PSQ), quantitative methylation-specific PCR (qMSP) and immunohistochemistry (IHC), methylation-sensitive high resolution melting (MS-HRM) and NGS (Next Generation Sequencing) have been used to detect MGMT promoter methylation in gliomas. However, controversy remains about the most appropriate method to use for analyzing MGMT status. The MGMT promoter methylation status of a total of 350 gliomas and gangliogliomas was examined using PSQ, qMSP and IHC in parallel. Using PSQ as a recommended standard method, the sensitivity, specificity, positive/negative predictive value and correlation with the other assays were calculated. Among 350 glioma- and ganglioglioma cases, the MGMT promoter tested positive for methylation in 53.1%, 55.4%, and 70.3% of the cases by PSQ, qMSP and IHC, respectively. The sensitivity and specificity of qMSP were 97.8% and 92.7%, respectively. Twelve cases that tested positive for methylation using qMSP were negative according to PSQ, and four cases that were negative according to qMSP tested positive according to PSQ. The concordance rate between PSQ and qMSP was 90.8%. The sensitivity and specificity of IHC for the detection of MGMT at the protein level were 84.4% and 45.7%, respectively. The concordance rate between PSQ and IHC was 30.8%.This study demonstrated that qMSP is an effective and rapid detection method for routine use in pathology laboratories for the identification of MGMT promoter methylation. A combination of IHC and qMSP assays can provide high sensitivity and specificity for the prediction of MGMT status. A few cases that tested negative with PSQ did harbor MGMT promoter methylation, as confirmed by qMSP and sequencing, and this subgroup of patients may benefit from temozolomide.



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Synergy between air pollution and urban meteorological changes through aerosol-radiation-diffusion feedback―A case study of Beijing in January 2013

Publication date: Available online 10 October 2017
Source:Atmospheric Environment
Author(s): Mizuo Kajino, Hiromasa Ueda, Zhiwei Han, Rei Kudo, Yayoi Inomata, Hidenori Kaku
The interactions of aerosol-radiation-stratification-turbulence-cloud processes during a severe haze event in Beijing in January 2013 were studied using a numerical model. For the clear days, solar radiation flux was reduced by approximately 15% and surface temperature was slightly decreased from 0 to 0.5 K throughout the day and night, except for a 1.4 K decrease around sunrise when fog was presented. The longwave radiation cooling was intensified by the fog or drizzle droplets near the top of the fog layer. Thus, in Beijing, both in the daytime and at night, the surface air temperature was decreased by air pollutants. In the presence of the low-level stratus and light precipitation, the modification of meteorology by aerosols was amplified and changed the wind speed and direction much more significantly compared to clear days. The non-linear effect (or positive feedback) of pollutant emission control on the surface air concentration was newly assessed―severe air pollution leads to the intensification of stable stratification near the surface at night and delays the evolution of the mixing layer, which in turn causes more severe air pollution. The non-linear effect was not significant for the current emission levels in the current case, approximately 10%. In another word, the mixing ratio of aerosols became higher by 10% due to their radiation effects.



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Involvement of mitochondrial pathway in environmental metal pollutant lead-induced apoptosis of chicken liver: perspectives from oxidative stress and energy metabolism

Abstract

This study aimed to investigate the possible mechanisms of environmental metal pollutant lead (Pb)-induced apoptosis in chicken. Forty 8-day-old healthy chickens were randomly assigned to two groups (n = 20/group) after raising standard commercial diet and drinking water for 1 week: including control group and Pb group ((CH₃COO)₂Pb 350 mg/L of drinking water); the chickens were given euthanasia and collected livers at 90 days. A significant increase of apoptosis rate were found in Pb group and Pb induced obvious ultrastructural changes of chicken liver. The mRNA levels of glycometabolism key enzymes were significantly lower in Pb group than those in controls. Higher levels of malondialdehyde (MDA) and nitric oxide (NO) were observed in Pb group; the activities of antioxidant enzymes and ATPases were significantly lower in Pb group than those in controls, while the inducible nitric oxide synthase (iNOS) activity was on the contrary. The mRNA and protein levels of pro-apoptotic genes were all lower in Pb group than those in controls. Altogether, Pb-induced mitochondrial swelling and nuclear chromatin condensation, oxidative stress, energy metabolism disorder, thereby lead to apoptosis via mitochondrial pathway in chicken liver, suggesting that Pb-induced mitochondrial pathway apoptosis plays an important role in the mechanisms of Pb cytotoxicity to chicken liver.

http://ift.tt/2xuUX4k

Organ-on-chip models of cancer metastasis for future personalized medicine: From chip to the patient

Publication date: December 2017
Source:Biomaterials, Volume 149
Author(s): D. Caballero, S. Kaushik, V.M. Correlo, J.M. Oliveira, R.L. Reis, S.C. Kundu
Most cancer patients do not die from the primary tumor but from its metastasis. Current in vitro and in vivo cancer models are incapable of satisfactorily predicting the outcome of various clinical treatments on patients. This is seen as a serious limitation and efforts are underway to develop a new generation of highly predictive cancer models with advanced capabilities. In this regard, organ-on-chip models of cancer metastasis emerge as powerful predictors of disease progression. They offer physiological-like conditions where the (hypothesized) mechanistic determinants of the disease can be assessed with ease. Combined with high-throughput characteristics, the employment of organ-on-chip technology would allow pharmaceutical companies and clinicians to test new therapeutic compounds and therapies. This will permit the screening of a large battery of new drugs in a fast and economic manner, to accelerate the diagnosis of the disease in the near future, and to test personalized treatments using cells from patients. In this review, we describe the latest advances in the field of organ-on-chip models of cancer metastasis and their integration with advanced imaging, screening and biosensing technologies for future precision medicine applications. We focus on their clinical applicability and market opportunities to drive us forward to the next generation of tumor models for improved cancer patient theranostics.



http://ift.tt/2wL8ost

Translating the role of osteogenic-angiogenic coupling in bone formation: Highly efficient chitosan-pDNA activated scaffolds can accelerate bone regeneration in critical-sized bone defects

Publication date: December 2017
Source:Biomaterials, Volume 149
Author(s): Rosanne M. Raftery, Irene Mencía Castaño, Gang Chen, Brenton Cavanagh, Brian Quinn, Caroline M. Curtin, Sally Ann Cryan, Fergal J. O'Brien
The clinical translation of bioactive scaffolds for the treatment of large segmental bone defects has remained a challenge due to safety and efficacy concerns as well as prohibitive costs. The design of an implantable, biocompatible and resorbable device, which can fill the defect space, allow for cell infiltration, differentiation and neovascularisation, while also recapitulating the natural repair process and inducing cells to lay down new bone tissue, would alleviate the problems with existing treatments. We have developed a gene-activated scaffold platform using a bone-mimicking collagen hydroxyapatite scaffold loaded with chitosan nanoparticles carrying genes encoding osteogenic (BMP-2) and angiogenic (VEGF) proteins. With a single treatment, protein expression by mesenchymal stem cells (MSCs) seeded onto the scaffold is sustained for up to 28 days and is functional in inducing MSC osteogenesis. The in vivo safety and efficacy of this gene-activated scaffold platform was demonstrated resulting in the successful transfection of host cells, abrogating the requirement for multiple procedures to isolate cells or ex vivo cell culture. Furthermore, the level of bone formation at the exceptionally early time-point of 28 days was comparable to that achieved following recombinant BMP-2 protein delivery after 8 weeks in vivo, without the adverse side effects and at a fraction of the cost. This naturally derived cell-free gene-activated scaffold thus represents a new 'off-the-shelf' product capable of accelerating bone repair in critical-sized bone defects.



http://ift.tt/2g7Pby7

Relapsing polychondritis, an underestimated dermatological urgency: case report and literature review

Abstract

Background

Relapsing polychondritis is an autoimmune multisystemic disease with primary chondral involvement. Its high mortality and morbidity make it a real clinical challenge.

Case description

A 32-year-old woman with a history of relapsing polychondritis, refractory to multiple treatments, with multisystem compromise, imminent risk of death due to severe tracheobronchial damage and difficult ventilatory support, and successful treatment with infliximab.

Discussion and evaluation

Several treatments have been described in the literature, such as nonsteroidal anti-inflammatory drugs, corticosteroids, dapsone, azathioprine, cyclosporine, cyclophosphamide, and methotrexate. However, the cases refractory to conventional therapy may lead to chronicity, irreversibility, and death. As a result, a third-line therapy could improve the prognosis of these patients.

Conclusions

Biological therapy is a good option for disease control and quality of life improvement. In addition, the physician should consider these treatments to avoid the chronicity and risk of death of these patients.

http://ift.tt/2ycul6R

Surgical management of apocrine hidrocystoma on the penile shaft

http://ift.tt/2xwn2mY

Macrophage subtypes in recurrent nodular basal cell carcinoma after Mohs micrographic surgery

Abstract

Background

The macrophages associated with solid tumors are related to the progression or regression of tumors, depending on the differentiation in M1 or M2. M2 subtype promotes angiogenesis, remodeling, and tissue repair (tumor proliferation). In contrast, M1 produces toxic mediators and presents antigens, destroying microorganisms and tumor cells. The microenvironment of most aggressive forms of basal cell carcinoma (BCC) shows an increase in macrophages due to M2 phenotype compared to noninvasive forms. The treatment of nodular BCC by Mohs micrographic surgery (MMS) provides high cure rates, but relapses can occur.

Aims

To compare the total population of macrophages and their subpopulations M1 and M2 in cases of recurrent and nonrecurrent nodular BCC after excision by MMS.

Materials & Methods

Histological sections obtained from paraffin blocks of nine cases of recurrent nodular BCC after MMS and 18 cases of nonrecurrent nodular BCC operated by MMS were immunostained for iNOS, CD204, CD163, and CD68. The expression of these markers was analyzed by image analysis.

Results

No significant differences were found between the groups in relation to the average percentage of M1 cells, M2 cells, and total cells.

Discussion and Conclusion

A relationship was not seen between tumor-associated macrophages (TAM) and tumor recurrence.

http://ift.tt/2ycW2wx

Radiation, radionuclides and bacteria: An in-perspective review

Publication date: December 2017
Source:Journal of Environmental Radioactivity, Volume 180
Author(s): Arpit Shukla, Paritosh Parmar, Meenu Saraf
There has been a significant surge in consumption of radionuclides for various academic and commercial purposes. Correspondingly, there has been a considerable amount of generation of radioactive waste. Bacteria and archaea, being earliest inhabitants on earth serve as model microorganisms on earth. These microbes have consistently proven their mettle by surviving extreme environments, even extreme ionizing radiations. Their ability to accept and undergo stable genetic mutations have led to development of recombinant mutants that are been exploited for remediation of various pollutants such as; heavy metals, hydrocarbons and even radioactive waste (radwaste). Thus, microbes have repeatedly presented themselves to be prime candidates suitable for remediation of radwaste. It is interesting to study the behind-the-scenes interactions these microbes possess when observed in presence of radionuclides. The emphasis is on the indigenous bacteria isolated from radionuclide containing environments as well as the five fundamental interaction mechanisms that have been studied extensively, namely; bioaccumulation, biotransformation, biosorption, biosolubilisation and bioprecipitation. Application of microbes exhibiting such mechanisms in remediation of radioactive waste depends largely on the individual capability of the species. Challenges pertaining to its potential bioremediation activity is also been briefly discussed. This review provides an insight into the various mechanisms bacteria uses to tolerate, survive and carry out processes that could potentially lead the eco-friendly approach for removal of radionuclides.

Graphical abstract

http://ift.tt/2yBCvXU

Examining temporal alterations in Social Anxiety Disorder and Posttraumatic Stress Disorder: The relation between autobiographical memory, future goals, and current self-views

Publication date: Available online 9 October 2017
Source:Journal of Anxiety Disorders
Author(s): Julie Krans, Manon Peeters, Gérard Näring, Adam D. Brown, June de Bree, Agnes van Minnen
The self is a multi-faceted and temporally dynamic construct reflecting representations and beliefs about identity in the past, present, and future. Clinical studies have shown that individuals with Posttraumatic Stress Disorder (PTSD) and Social Anxiety Disorder (SAD) exhibit alterations in self-related processing but these studies have focused primarily on memory. Few studies in PTSD and SAD have examined self-related processing for the present and future, and no studies have directly compared these processes across these two disorders. Individuals diagnosed with PTSD (n=21), SAD (n=21), and healthy controls (n=21) completed cognitive tasks related to the past, present, and future. Disorder congruent temporal alterations were found across both disorders. Further, regression analyses revealed that trauma-related memories were significantly predicted by future goals related to the trauma, whereas social anxiety-related recall was predicted by current socially anxious self-views. Thus, although self-related processing may be common in PTSD and SAD, those aspects of the self most strongly associated with disorder-congruent recall differ by disorder. Self-alterations may be modifiable and developing a better understanding of past, present, and future self-processing might aid in the development of interventions that target these process.



http://ift.tt/2g7DOGf

Acute pancreatitis with eruptive xanthoma

Eruptive xanthomas are benign skin lesions caused by localised deposition of lipids in the dermis. Xanthomas can present as early manifestations of systemic disorders, which are typically caused by elevated levels of serum triglycerides and uncontrolled diabetes. Early recognition and treatment of the underlying condition decreases morbidity and mortality. After treatment of the underlying metabolic disorders, lesions mostly disappear without leaving scars. We present a case with multiple yellowish, erythematous papules on the extremities suggestive of eruptive xanthomas admitted to our hospital with acute pancreatitis.

http://ift.tt/2g5M9u8

Ogilvies syndrome treated with an emergency laparotomy, right hemicolectomy and end ileostomy

Acute colonic pseudo-obstruction (ACPO), or Ogilvie's syndrome, is a rare clinical entity in which there is massive non-toxic colonic dilatation in the absence of a mechanically obstructing lesion. It is an important yet poorly recognised cause of surgical morbidity and mortality occurring typically in elderly patients with multiple comorbidities. ACPO can often be reversed conservatively with colonoscopic or nasogastric decompression. Surgical intervention is seldom necessary. We present a case of Ogilvie's syndrome in which a healthy 76-year-old man developed life-threatening pseudo-obstruction following rib polytrauma after a mechanical fall. Pneumatosis coli was evident radiologically, prompting emergency exploratory laparotomy. Operative findings of serosal tearing and ischaemic colitis necessitated treatment with right hemicolectomy and ileostomy formation. Microbiological and histopathological analyses proved negative for inflammatory, obstructive and infectious colitides. The case emphasises the importance of early recognition and timely intervention in the management of this rare yet potentially fatal cause of megacolon.

http://ift.tt/2hYaN0n

ANCA and IgA glomerulonephritis all in one: prognosis and complications

We present the case of a 75-year-old Hispanic woman with known stage 3 chronic kidney disease, long-standing hypertension and type 2 diabetes mellitus who presented with right-sided abdominal pain and acute kidney injury, nephrotic range proteinuria with positive antimyeloperoxidase antibody. A renal biopsy revealed IgA nephropathy with superimposed pauci-immune antineutrophilic cytoplasmic antibody (ANCA)-associated crescentic glomerulonephritis. The patient was treated with pulse intravenous methylprednisolone, cyclophosphamide and plasmapheresis. One week after her second dose of cyclophosphamide, she was readmitted for infectious complications including influenza A respiratory infection, Rothia bacteraemia associated with diarrhoea and herpes zoster of the trunk. In this report, we review the prevalence, treatment and prognosis of coexistent IgA nephropathy and pauci-immune ANCA-associated crescentic glomerulonephritis. We propose that a reduced-dose treatment regimen should be considered in elderly patients due to their higher risk of infectious complications. Current literature suggests that this treatment approach may reduce infectious complications without compromising therapeutic efficacy.

http://ift.tt/2g74pTS

Knee upside down

We present a case of a 19-year-old woman with a forced hyperextension trauma of the knee causing a posteromedial fracture, a medial meniscus root tear and rupture of the posterior cruciate ligament. The posteromedial fracture of the tibial plateau was treated operatively with open reduction and internal fixation. Anatomical reconstruction was achieved. Postoperative treatment included unlimited flexion and minimal weight bearing. After 3 months, the patient had minimal pain after weight bearing and returned to preoperative range of motion.

http://ift.tt/2g7cRlZ

Coating of silicone with mannoside-PAMAM dendrimers to enhance formation of non-pathogenic Escherichia coli biofilms against colonization of uropathogens

Publication date: Available online 9 October 2017
Source:Acta Biomaterialia
Author(s): Zhiling Zhu, Fei Yu, Haoqing Chen, Jun Wang, Analette I. Lopez, Quan Chen, Siheng Li, Yuyu Long, Rabih O. Darouiche, Richard A. Hull, Lijuan Zhang, Chengzhi Cai
Bacterial interference using non-pathogenic Escherichia coli 83972 is a novel strategy for preventing catheter-associated urinary tract infection (CAUTI). Crucial to the success of this strategy is to establish a high coverage and stable biofilm of the non-pathogenic bacteria on the catheter surface. However, this non-pathogenic strain is sluggish to form biofilms on silicone as the most widely used material for urinary catheters. We have addressed this issue by modifying the silicone catheter surfaces with mannosides that promote the biofilm formation, but the stability of the non-pathogenic biofilms challenged by uropathogens over long-term remains a concern. Herein, we report our study on the stability of the non-pathogenic biofilms grown on propynylphenyl mannoside-modified silicone. The result shows that 94% non-pathogenic bacteria were retained on the modified silicone under >0.5 Pa shear stress. After being challenged by three multidrug-resistant uropathogenic isolates in artificial urine for 11 days, large amounts (>4 × 10⁶ CFU cm^-2) of the non-pathogenic bacteria remained on the surfaces. These non-pathogenic biofilms reduced the colonization of the uropathogens by >3.2-log.Statement of SignificanceIn bacterial interference, the non-pathogenic Escherichia coli strains are sluggish to form biofilms on the catheter surfaces, due to rapid removal by urine flow. We have demonstrated a solution to this bottleneck by pre-functionalization of mannosides on the silicone surfaces to promote E. coli biofilm formation. A pre-conjugated high affinity propynylphenyl mannoside ligand tethered to the nanometric amino-terminated poly(amido amine) (PAMAM) dendrimer is used for binding to a major E. coli adhesin FimH. It greatly improves the efficiency for the catheter modification, the non-pathogenic biofilm coverage, as well as the (long-term) stability for prevention of uropathogen infections.

Graphical abstract

http://ift.tt/2g5FSyA

Proteomics of Periodontal Pocket

Abstract

Purpose of Review

This study aims to present and evaluate the findings of the literature referring to proteomic analysis of the periodontal pocket aimed to identify potential biomarkers for periodontal disease.

Recent Findings

A comprehensive examination of data from "shotgun" proteomic analysis has shown that a number of human proteins, previously not extensively investigated in the literature, have emerged as new candidates. Proteins relevant to various biological functions such as actin, profilin, hemoglobin, plastins, alpha-amylase, matrix metalloproteinases, keratins, histones, annexins, antimicrobial peptides including histatins, S-100A9, cathelicidin-related peptide-37 (LL-37), human neutrophil peptides (HNP)-1, -2, and -3, statherin, and cystatins are commonly identified in gingival crevicular fluid (GCF) by proteomic analysis and are upregulated in periodontal disease and therefore could serve as biomarkers.

Conclusions

Proteomic analysis has provided a new insight into the search for biomarkers of periodontal disease presence, progression, prognosis, and endpoints of treatment. Data derived should be validated by larger scale studies, including significant subject samples. These second-stage studies should focus on evaluating the importance of these proposed new biomarkers using standardized procedures.

http://ift.tt/2kBVYBt

Periodontal Abscess: a Review and the Role of Antimicrobial Therapy

Abstract

Purpose of Review

The aim was to summarize current knowledge about periodontal abscesses and describe recent research on antimicrobial treatment.

Recent Findings

For periodontal abscess treatment, antimicrobial therapy is implemented as an adjunct modality to subgingival debridement and/or abscess drainage. Among available systemic antimicrobial agents, amoxicillin (plus clavulanate), metronidazole, and azithromycin are often used with good clinical results. In our studies of patients with acute periodontal lesions, systemic administration of a new fluoroquinolone, sitafloxacin, yielded a significant improvement in clinical parameters, and was effective against subgingival bacteria, with no significant impact on the antimicrobial susceptibility of periodontal bacteria.

Summary

Plaque control during initial periodontal therapy or maintenance care is critical for the prevention and treatment of periodontal abscesses. In the case of acute periodontal abscesses, drainage is considered first. When drainage is not possible or insufficient, antimicrobial therapy should then be considered. Microbiological testing can contribute to the successful treatment.

http://ift.tt/2xsUiQN

Talin regulates integrin {beta}1 dependent and independent cell functions in ureteric bud development [RESEARCH ARTICLE]

Sijo Mathew, Riya J. Palamuttam, Glenda Mernaugh, Harini Ramalingam, Zhenwei Lu, Ming-Zhi Zhang, Shuta Ishibe, David R. Critchley, Reinhard Fässler, Ambra Pozzi, Charles R. Sanders, Thomas J. Carroll, and Roy Zent

Kidney collecting system development requires integrin-dependent cell-extracellular matrix interactions. Integrins, are heterodimeric transmembrane receptors consisting of α and β subunits and critical integrins in the kidney collecting system express the β1subunit. The β1 cytoplasmic tail has two NPxY motifs that mediate functions by binding to cytoplasmic signaling and scaffolding molecules. Talins, scaffolding proteins that bind to the membrane proximal NPxY motif, are proposed to activate integrins and link them to the actin cytoskeleton. We defined the role of talin binding to the β1 proximal NPxY motif in the developing kidney collecting system in mice that selectively express a Y-to-A mutation in this motif. The mice developed a hypoplastic dysplastic collecting system. Collecting duct cells expressing this mutation had moderate abnormalities in cell adhesion, migration, proliferation and growth factor dependent signaling. In contrast, mice lacking talins in the developing ureteric bud developed kidney agenesis and collecting duct cells had severe cytoskeletal, adhesion and polarity defects. Thus, talins are essential for kidney collecting duct development through mechanisms that extend beyond those requiring binding to the β1 integrin subunit NPxY motif.

http://ift.tt/2zcagfB

Myc cooperates with beta-catenin to drive gene expression in the nephron progenitor cells [RESEARCH ARTICLE]

Xinchao Pan, Courtney M. Karner, and Thomas J. Carroll

For organs to achieve their proper size, the processes of stem cell renewal and differentiation must be tightly regulated. We previously showed that in the developing kidney, Wnt9b regulates distinct beta-catenin-dependent transcriptional programs in the renewing and differentiating populations of the nephron progenitor cells. How beta-catenin stimulated these two distinct programs was unclear. Here, we show that beta-catenin cooperates with the transcription factor Myc to activate the progenitor renewal program. Although in multiple contexts Myc is a target of beta-catenin, our characterization of a cell type specific enhancer for the Wnt9b/beta-catenin target gene Fam19a5 shows that Myc and beta-catenin cooperate to activate gene expression controlled by this element. This appears to be a more general phenomenon as we find that Myc is required for the expression of every Wnt9b/beta-catenin progenitor renewal target assessed as well as for proper nephron endowment in vivo. This study suggests that within the developing kidney, tissue-specific beta-catenin activity is regulated by cooperation with cell type-specific transcription factors. This finding not only provides insight into the regulation of beta-catenin target genes in the developing kidney, but will also advance our understanding of progenitor cell renewal in other cell types/organ systems where Myc and beta-catenin are coexpressed.

http://ift.tt/2xsHLwR

The African Zika virus MR-766 is more virulent and causes more severe brain damage than current Asian lineage and Dengue virus [RESEARCH ARTICLE]

Qiang Shao, Stephanie Herrlinger, Ya-Nan Zhu, Mei Yang, Forrest Goodfellow, Steven L. Stice, Xiao-Peng Qi, Melinda A. Brindley, and Jian-Fu Chen

The Zika virus (ZIKV) has two lineages, Asian and African, and their impact on developing brains has not been compared. Dengue virus (DENV) is a close family member of ZIKV and co-circulates with ZIKV. Here we performed intracerebral inoculation of embryonic mouse brains with dengue virus 2 (DENV2), and found that DENV2 is sufficient to cause smaller brain size due to increased cell death in neural progenitor cells (NPCs) and neurons. Compared to the currently circulating Asian lineage of ZIKV (MEX1-44), DENV2 grows slower, causes less neuronal death, and fails to cause postnatal animal death. Surprisingly, our side-by-side comparison uncovered that African ZIKV isolate (MR-766) is more potent in causing brain damage and postnatal lethality than MEX1-44. In comparison to MEX1-44, MR-766 grows faster in NPCs and in the developing brain, and causes more pronounced cell death in NPCs and neurons, resulting in more severe neuronal loss. Together, these results reveal that DENV2 is sufficient to cause smaller brain sizes, and suggest that the ZIKV African lineage is more virulent and causes more severe brain damage than the Asian lineage.

http://ift.tt/2zaAXRv

Graf regulates hematopoiesis through GEEC endocytosis of EGFR [RESEARCH ARTICLE]

Sungdae Kim, Minyeop Nahm, Najin Kim, Yumi Kwon, Joohyung Kim, Sukwoo Choi, Eun Young Choi, Jiwon Shim, Cheolju Lee, and Seungbok Lee

GTPase regulator associated with focal adhesion kinase-1 (Graf1) is an essential component of the GPI-enriched endocytic compartment (GEEC) endocytosis pathway. Mutations in the human graf1 gene are associated with acute myeloid leukemia (AML), but its normal role in myeloid cell development remains unclear. We show that Graf, the Drosophila ortholog of Graf1, is expressed and specifically localizes to GEEC endocytic membranes in macrophage-like plasmatocytes. We also find that loss of Graf impairs GEEC endocytosis, enhances EGFR signaling, and induces a plasmatocyte overproliferation phenotype that requires the EGFR signaling cascade. Mechanistically, Graf-dependent GEEC endocytosis serves as a major route of EGFR internalization at high, but not low, doses of the predominant Drosophila EGFR ligand Spitz (Spi) and is indispensable for efficient EGFR degradation and signal attenuation. Finally, Graf interacts directly with EGFR in a receptor ubiquitination-dependent manner, suggesting a mechanism by which Graf promotes GEEC endocytosis of EGFR at high Spi. Based on our findings, we propose a model in which Graf functions to downregulate EGFR signaling by facilitating Spi-induced receptor internalization through GEEC endocytosis, thereby restraining plasmatocyte proliferation.

http://ift.tt/2xsHIRH

Positive experiences related to living with tinnitus: A cross-sectional survey

Abstract

Objective

The aim of this study was to gain insights related to positive experiences reported by adults with tinnitus living in the UK.

Design

A cross-sectional survey design was used in a sample of adults with tinnitus who were interested in undertaking an Internet-based intervention for tinnitus.

Setting

The study was UK wide and data collection was online.

Participants

Participants consisted of 240 adults (137 males, 103 females), with an average age of 48.16 years and average tinnitus duration of 11.52 years (SD: 11.88).

Main outcome measures

Tinnitus severity was measured by means of the Tinnitus Functional Index. To evaluate the secondary effects of tinnitus, the Insomnia Severity Index, the Hearing Handicap Inventory for Adults-Screening Version and the Cognitive Failures Questionnaires were administered. Positive experiences related to tinnitus were explored using an open-ended question format.

Results

Around a third of participants (32.5%) reported positive experiences associated with tinnitus. The number of positive responses ranged from one to eight responses per participant, although there were fewer participants with more than one positive response. The predominant themes concerned: (1) coping; (2) personal development; (3) support, and to a lesser extent (4) outlook. Younger participants, those with a lower hearing disability and those with fewer cognitive failures were more likely to report positive experiences associated with having tinnitus.

Conclusions

This study has identified that personal development and a positive outlook is possible despite experiencing tinnitus. Ways to facilitate positive experiences related to tinnitus should be promoted, as these may reduce the negative consequences associated with tinnitus.

The most prevalent positive theme was the ability to cope with tinnitus. Positive experiences were also drawn from having clinical and other support networks. This highlights the importance of providing tinnitus interventions that can assist people in coping with tinnitus, particularly to those less likely to relate tinnitus to any positive experiences. Those most likely to be helped include those who are older with greater cognitive difficulties and a greater hearing disability.

This article is protected by copyright. All rights reserved.

http://ift.tt/2gr5Zx4

Positive experiences related to living with tinnitus: A cross-sectional survey

Abstract

Objective

The aim of this study was to gain insights related to positive experiences reported by adults with tinnitus living in the UK.

Design

A cross-sectional survey design was used in a sample of adults with tinnitus who were interested in undertaking an Internet-based intervention for tinnitus.

Setting

The study was UK wide and data collection was online.

Participants

Participants consisted of 240 adults (137 males, 103 females), with an average age of 48.16 years and average tinnitus duration of 11.52 years (SD: 11.88).

Main outcome measures

Tinnitus severity was measured by means of the Tinnitus Functional Index. To evaluate the secondary effects of tinnitus, the Insomnia Severity Index, the Hearing Handicap Inventory for Adults-Screening Version and the Cognitive Failures Questionnaires were administered. Positive experiences related to tinnitus were explored using an open-ended question format.

Results

Around a third of participants (32.5%) reported positive experiences associated with tinnitus. The number of positive responses ranged from one to eight responses per participant, although there were fewer participants with more than one positive response. The predominant themes concerned: (1) coping; (2) personal development; (3) support, and to a lesser extent (4) outlook. Younger participants, those with a lower hearing disability and those with fewer cognitive failures were more likely to report positive experiences associated with having tinnitus.

Conclusions

This study has identified that personal development and a positive outlook is possible despite experiencing tinnitus. Ways to facilitate positive experiences related to tinnitus should be promoted, as these may reduce the negative consequences associated with tinnitus.

The most prevalent positive theme was the ability to cope with tinnitus. Positive experiences were also drawn from having clinical and other support networks. This highlights the importance of providing tinnitus interventions that can assist people in coping with tinnitus, particularly to those less likely to relate tinnitus to any positive experiences. Those most likely to be helped include those who are older with greater cognitive difficulties and a greater hearing disability.

This article is protected by copyright. All rights reserved.

http://ift.tt/2gr5Zx4

Who Would Be Branded With Failure?.

Author: Stevenson, Lynne Warner MD

Page: 1359-1361

http://ift.tt/2zazMBz

Prolonged, Uninterrupted Sedentary Behavior and Glycemic Biomarkers Among US Hispanic/Latino Adults: The HCHS/SOL (Hispanic Community Health Study/Study of Latinos).

Author: Diaz, Keith M. PhD; Goldsmith, Jeff PhD; Greenlee, Heather ND, PhD; Strizich, Garrett MPH; Qi, Qibin PhD; Mossavar-Rahmani, Yasmin PhD; Vidot, Denise C. PhD; Buelna, Christina MA; Brintz, Carrie E. PhD; Elfassy, Tali PhD; Gallo, Linda C. PhD; Daviglus, Martha L. MD, PhD; Sotres-Alvarez, Daniela DrPH; Kaplan, Robert C. PhD

Page: 1362-1373

http://ift.tt/2xtULSX

Effect of Ferric Carboxymaltose on Exercise Capacity in Patients With Chronic Heart Failure and Iron Deficiency.

Author: van Veldhuisen, Dirk J. MD; Ponikowski, Piotr MD; van der Meer, Peter MD; Metra, Marco MD; Bohm, Michael MD; Doletsky, Artem MD; Voors, Adriaan A. MD; Macdougall, Iain C. MD; Anker, Stefan D. MD; Roubert, Bernard MSc; Zakin, Lorraine MD; Cohen-Solal, Alain MD; On Behalf of the EFFECT-HF Investigators

Page: 1374-1383

http://ift.tt/2zbelQY

"Pumping Iron" to Improve Exercise Performance in Heart Failure: New Data and New Guidelines.

Author: Katz, Stuart D. MD, MS

Page: 1384-1386

http://ift.tt/2xsTbk5

Outcomes Associated With Extraction Versus Capping and Abandoning Pacing and Defibrillator Leads.

Author: Pokorney, Sean D. MD, MBA; Mi, Xiaojuan PhD; Lewis, Robert K. MD, MBA, PhD; Greiner, Melissa MS; Epstein, Laurence M. MD; Carrillo, Roger G. MD, MBA; Zeitler, Emily P. MD, MHS; Al-Khatib, Sana M. MD, MHS; Hegland, Donald D. MD; Piccini, Jonathan P. MD, MHS

Page: 1387-1395

http://ift.tt/2zazOcF

Tomo-Seq Identifies SOX9 as a Key Regulator of Cardiac Fibrosis During Ischemic Injury.

Author: Lacraz, Gregory P.A. MSc, PhD *; Junker, Jan Philipp MSc, PhD *; Gladka, Monika M. MSc, PhD; Molenaar, Bas MSc; Scholman, Koen T. MSc; Vigil-Garcia, Marta MSc; Versteeg, Danielle BS; de Ruiter, Hesther BS; Vermunt, Marit W. MSc, PhD; Creyghton, Menno P. MSc, PhD; Huibers, Manon M.H. MSc, PhD; de Jonge, Nicolaas MD; van Oudenaarden, Alexander MSc, PhD; van Rooij, Eva MSc, PhD

Page: 1396-1409

http://ift.tt/2xuaUYk

Spatial Gene Profiling in the Ischemic Heart: Fibroblasts Put on Their SOX.

Author: Khalil, Hadi PhD; Maillet, Marjorie PhD; Molkentin, Jeffery D. PhD

Page: 1410-1411

http://ift.tt/2zb7Fm3

Interferon Regulatory Factor 4 Inhibits Neointima Formation by Engaging Kruppel-Like Factor 4 Signaling.

Author: Cheng, Wen-Lin MD *; She, Zhi-Gang MD, PhD *; Qin, Juan-Juan MD *; Guo, Jun-Hong PhD; Gong, Fu-Han MD; Zhang, Peng PhD; Fang, Chun PhD; Tian, Song BS; Zhu, Xue-Yong BS; Gong, Jun PhD; Wang, Zhi-Hua PhD; Huang, Zan PhD; Li, Hongliang MD, PhD

Page: 1412-1433

http://ift.tt/2xtKeHk

Wine and Cardiovascular Health: A Comprehensive Review.

Author: Haseeb, Sohaib BSc; Alexander, Bryce BSc; Baranchuk, Adrian MD

Page: 1434-1448

http://ift.tt/2zaPMUq

Scientists Correct a Pathogenic Gene Mutation in Human Embryos.

Author: Hampton, Tracy PhD

Page: 1449-1450

http://ift.tt/2xuowmr

Sedentary Behavior and Subclinical Cardiac Injury: Results From the Dallas Heart Study.

Author: Harrington, Josephine L. MD; Ayers, Colby MS; Berry, Jarett D. MD; Omland, Torbjorn MD, PhD; Pandey, Ambarish MD; Seliger, Stephen L. MD, MS; Ballantyne, Christie M. MD; Kulinski, Jacquelyn MD; deFilippi, Christopher R. MD; de Lemos, James A. MD

Page: 1451-1453

http://ift.tt/2zd1IF8

Letter by Vos et al Regarding Article, "Primary Prevention With Statin Therapy in the Elderly: New Meta-Analyses From the Contemporary JUPITER and HOPE-3 Randomized Trials".

Author: Vos, Eddie MEng; Biron, Pierre MD; Rose, Colin P. MD, PhD

Page: 1454-1455

http://ift.tt/2xtQ0so

Letter by Kleipool et al Regarding Article, "Primary Prevention With Statin Therapy in the Elderly: New Meta-Analyses From the Contemporary JUPITER and HOPE-3 Randomized Trials".

Author: Kleipool, Emma E.F. MD; Peters, Mike J.L. MD, PhD; Muller, Majon MD, PhD

Page: 1456-1457

http://ift.tt/2zbRwge

Bacteremia after supragingival scaling and dental extraction: culture and molecular analyses

Abstract

Objective

To study the incidence and magnitude of bacteremia after dental extraction and supragingival scaling.

Subjects and Methods

Blood samples were taken before and 5 and 30 minutes after dental extraction and supragingival scaling from individuals at high (n=42) or negligible risk (n=53) for infective endocarditis. The former received prophylactic antibiotic therapy. Samples were subjected to aerobic and anaerobic culture and quantitative real-time polymerase chain reaction to determine the incidence of bacteremia and total bacterial levels.

Results

Patients who did not receive prophylactic antibiotic therapy had a higher incidence of positive blood cultures (26% 5 min after extraction) than patients who received prophylactic antibiotic therapy (0% 5 min after extraction; P=.01). Molecular analysis did not reveal significant differences in the incidence or magnitude of bacteremia between the two patient groups either 5 or 30 minutes after each of the procedures evaluated. Extraction was associated with higher incidence of bacteremia than supragengival scaling by molecular analysis (P=.05).

Conclusions

Molecular methods revealed that dental extraction and supragingival scaling were associated with similar incidence of bacteremia in groups receiving or not prophylactic antibiotic therapy. However, blood culture revealed that antibiotic therapy reduced viable cultivable bacteria in the bloodstream in the extraction group.

This article is protected by copyright. All rights reserved.

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Have we pushed the needle for treatment of Type 1 diabetes?

Nida Naushad | Ana Luisa Perdigoto | Jinxiu Rui | Kevan C Herold

http://ift.tt/2g7t76L

Pathogenesis of infections in HIV-infected individuals: insights from primary immunodeficiencies

Qian Zhang | Pierre Frange | Stéphane Blanche | Jean-Laurent Casanova

http://ift.tt/2yBq9PF

Landmarks for the preservation of the middle temporal artery during mastoid surgery: Cadaveric dissection study

The middle temporal artery flap is a vascularized periosteal flap that is highly useful for otologic reconstruction including the middle cranial fossa, mastoidectomy defect, and external auditory canal. The course of the artery is close to the external auditory canal and is easily injured during preliminary exposure and elevation of flaps.

http://ift.tt/2ycuHuv

The role of explorative tympanotomy in patients with sudden sensorineural hearing loss with and without perilymphatic fistula

The purpose of this study was to describe the role of explorative tympanotomy in patients with Profound Sudden Sensorineural Hearing Loss (SSNHL) without clinical evidence of perilymphatic or labyrinthine fistula and to compare intraoperative findings with the postoperative hearing outcome.

http://ift.tt/2gqglwW

Outcome of spray cryotherapy plus functional endoscopic sinus surgery on management of healing in nasal polyposis

Nasal Polyposis is a benign tumor in nasal or paranasal mucosa, which confronts difficulties in management of healing after treatments with surgery. The aim of this study was to evaluate the effects of Spray Cryotherapy (SCT) on management of healing in patients with nasal polyposis who undergone functional endoscopic sinus surgery.

http://ift.tt/2yb7UiF

Landmarks for the preservation of the middle temporal artery during mastoid surgery: Cadaveric dissection study

The middle temporal artery flap is a vascularized periosteal flap that is highly useful for otologic reconstruction including the middle cranial fossa, mastoidectomy defect, and external auditory canal. The course of the artery is close to the external auditory canal and is easily injured during preliminary exposure and elevation of flaps.

http://ift.tt/2ycuHuv

The role of explorative tympanotomy in patients with sudden sensorineural hearing loss with and without perilymphatic fistula

The purpose of this study was to describe the role of explorative tympanotomy in patients with Profound Sudden Sensorineural Hearing Loss (SSNHL) without clinical evidence of perilymphatic or labyrinthine fistula and to compare intraoperative findings with the postoperative hearing outcome.

http://ift.tt/2gqglwW

Outcome of spray cryotherapy plus functional endoscopic sinus surgery on management of healing in nasal polyposis

Nasal Polyposis is a benign tumor in nasal or paranasal mucosa, which confronts difficulties in management of healing after treatments with surgery. The aim of this study was to evaluate the effects of Spray Cryotherapy (SCT) on management of healing in patients with nasal polyposis who undergone functional endoscopic sinus surgery.

http://ift.tt/2yb7UiF

Endoscopic versus microscopic approach in attic cholesteatoma surgery

Compare the outcomes of primary exclusive endoscopic ear surgery with those of the microscopic ear surgery in a group of patients affected by attic cholesteatoma.

http://ift.tt/2gqggcC

Payer database and geospatial analysis to evaluate practice patterns in treating allergy in North Carolina

The objective of this study was to characterize the delivery of allergy care in North Carolina using a large payer charge database and visualization techniques.

http://ift.tt/2ycuHdZ

Write your first article, but …

Publication date: Available online 9 October 2017
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): F. Rubin, H. Maisonneuve, C. Martin, O. Laccourreye




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Using principal trabecular orientation to differentiate joint loading orientation in the 3rd metacarpal heads of humans and chimpanzees

Publication date: December 2017
Source:Journal of Human Evolution, Volume 113
Author(s): Meir M. Barak, Emma Sherratt, Daniel E. Lieberman
If Wolff's law is valid, then quantifying the three-dimensional architecture of trabecular bone, specifically 3D principal trabecular orientation (3D-PTO), can reveal joint loading direction among different taxa. This study measured the architecture of trabecular bone in the 3rd metacarpal head of humans and chimpanzees, and then tested their association with expected joint loading direction. We postulate that since chimpanzees, unlike humans, directly load their metacarpal bones during knuckle-walking, trabecular structure in the dorsal aspect of the 3rd metacarpal head will be significantly more organized and robust in chimpanzees. To test this hypothesis, we micro-CT scanned the 3rd metacarpal from 11 chimpanzees and 12 humans. Three 6 mm volumes of interest (VOI; palmar, center and dorsal) were selected and trabecular bone properties and 3D-PTO were measured. The results revealed many similarities between humans and chimpanzees: in both taxa the dorsal VOI demonstrated the lowest bone volume fraction (BV/TV), the most rod-like trabecular structure, the fewest and thinnest trabeculae, and low organization of the trabecular architecture (degree of anisotropy). Nevertheless, 3D-PTO in the dorsal VOI differed significantly between humans and chimpanzees. While 3D-PTO in humans was clustered together and aligned nearly along the bone long axis, in chimpanzees 3D-PTO was divided into two distinct groups and aligned with an angle toward either the medial or lateral orientations. Our results suggest that loading effects on trabecular bone properties such as BV/TV might be partially constrained by genetic factors. On the other hand, 3D-PTO is continually affected by active loading (i.e., modeling) and thus may serve as a useful tool to infer differences in joint loading directions.



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Comparison of the renoprotective effect of dexmedetomidine and dopamine in high-risk renal patients undergoing cardiac surgery: A double-blind randomized study

Rabie Soliman, Mohamed Hussien

Annals of Cardiac Anaesthesia 2017 20(4):408-415

Objective: The purpose of the current study was to compare the renoprotective effects of continuous infusion of dexmedetomidine and dopamine in high-risk renal patients undergoing cardiac surgery. Design: A double-blind randomized study. Setting: Cardiac Centers. Patients: One hundred and fifty patients with baseline serum creatinine level ≥1.4 mg/dl were scheduled for cardiac surgery with cardiopulmonary bypass. Intervention: The patients were classified into two groups (each = 75): Group Dex – the patients received a continuous infusion of dexmedetomidine 0.4 μg/kg/h without loading dose during the procedure and the first 24 postoperative hours and Group Dopa – the patients received a continuous infusion of dopamine 3 μg/kg/min during the procedure and the first 24 postoperative hours. Measurements: The monitors included serum creatinine, creatinine clearance, blood urea nitrogen, and urine output. Main Results: The creatinine levels and blood urea nitrogen decreased at days 1, 2, 3, 4, and 5 in Dex group and increased in patients of Dopa group (P < 0.05). The creatinine clearance increased at days 1, 2, 3, 4, and 5 in Dex group and decreased in patients of Dopa group (P < 0.05). The amount of urine output was too much higher in the Dex group than the Dopa group (P < 0.05). Conclusions: The continuous infusion of dexmedetomidine during cardiac surgery has a renoprotective effect and decreased the deterioration in the renal function in high-risk renal patients compared to the continuous infusion of dopamine.

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A case report of combined radical pericardiectomy and beating heart coronary artery bypass grafting in a patient with tubercular chronic constrictive pericarditis with coronary artery disease

Gauranga Majumdar, Surendra Kumar Agarwal, Shantanu Pande, Bipin Chandra, Prabhat Tewari

Annals of Cardiac Anaesthesia 2017 20(4):465-467

We here report a successful midterm outcome following combined off-pump radical pericardiectomy and coronary artery bypass surgery (CABG) in a 65-year-old male patient who was suffering from chronic constrictive calcified tubercular pericarditis with coronary artery disease. Simultaneous off-pump CABG and radical pericardiectomy for nonsurgical constrictive pericarditis is reported very rarely in English literature.

http://ift.tt/2kBt0BN

Think beyond right bundle branch block in atrial septal defect

Monish S Raut, Arvind Verma, Arun Maheshwari, Ganesh Shivnani

Annals of Cardiac Anaesthesia 2017 20(4):475-476



http://ift.tt/2yUXst5

An uncommon intraoperative implantable cardiac device complication and subsequent troubleshooting

Rekha Suthar, Omar Viswanath, S Howard Wittels, Gerald P Rosen

Annals of Cardiac Anaesthesia 2017 20(4):483-484



http://ift.tt/2kCMc24

Bifid epiglottis: What perioperative physician should know about it?

Rupesh Yadav, Sohan Lal Solanki, Jeson R Doctor

Annals of Cardiac Anaesthesia 2017 20(4):479-480



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Comparison of dexmedetomidine and ketamine versus propofol and ketamine for procedural sedation in children undergoing minor cardiac procedures in cardiac catheterization laboratory

Vidya Sagar Joshi, Sandeep S Kollu, Ram Murti Sharma

Annals of Cardiac Anaesthesia 2017 20(4):422-426

Background: The ideal anaesthetic technique for management of paediatric patients scheduled to undergo cardiac catheterisation is still not standardised. Aim: To compare the effects of ketamine-propofol and ketamine-dexmedetomidine combinations on hemodynamic parameters and recovery time in paediatric patients undergoing minor procedures and cardiac catheterisation under sedation for various congenital heart diseases. Material and Methods: 60 children of either sex undergoing cardiac catheterisation were randomly assigned into two groups Dexmedetomidine-ketamine group (DK) and Propofol-ketamine (PK) of 30 patients each. All patients were premedicated with glycopyrrolate and midazolam (0.05mg/kg) intravenously 5-10 min before anaesthetic induction. Group 'DK'received dexmedetomidineiv infusion 1 μg/kg over 10 min + ketamine1mg/kg bolus, followed by iv infusion of dexmedetomidine 0.5μg/kg/hr and of ketamine1 mg/kg/hr. Group 'PK' received propofol 1mg/kg and ketamine 1mg/kg/hr for induction followed by iv infusion of propofol 100 μg/kg/hr and ketamine 1 mg/kg/hr for maintenance. Haemodynamic parameters and recovery time was recorded postoperatively. Statistical Analysis: Independent sample t test was used to compare the statistical significance of continuous variables of both the groups.Chi square test was used for numerical data like gender.Fischer exact test was applied for non parametric data like ketamine consumption. Results: We observed that heart rate in dexmedetomidine (DK) group was significantly lower during the initial 25 mins after induction compared to the propofol (PK) group. Recovery was prolonged in the DK group compared to the PK group (40.88 vs. 22.28 min). Even ketamine boluses consumption was higher in DK group. Conclusion: Use of dexmedetomidine-ketamine combination is a safe alternative, without any hemodynamic orrespiratory effects during the cardiac catheterization procedure but with some delayed recovery.

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Rhabdomyolysis and compartment syndrome in a bodybuilder undergoing minimally invasive cardiac surgery

Sebastian John Baxter, Madhusudan Rao Puchakayala, Vinayak N Bapat

Annals of Cardiac Anaesthesia 2017 20(4):453-455

Rhabdomyolysis is the result of skeletal muscle tissue injury and is characterized by elevated creatine kinase levels, muscle pain, and myoglobinuria. It is caused by crush injuries, hyperthermia, drugs, toxins, and abnormal metabolic states. This is often difficult to diagnose perioperatively and can result in renal failure and compartment syndrome if not promptly treated. We report a rare case of inadvertent rhabdomyolysis and compartment syndrome in a bodybuilder undergoing minimally invasive cardiac surgery. The presentation, differential diagnoses, and management are discussed. Hyperkalemia may be the first presenting sign. Early recognition and management are essential to prevent life-threatening complications.

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Ischemic mitral regurgitation

Praveen Kerala Varma, Neethu Krishna, Reshmi Liza Jose, Ashish Narayan Madkaiker

Annals of Cardiac Anaesthesia 2017 20(4):432-439

Ischemic mitral regurgitation (IMR) is a frequent complication of left ventricular (LV) global or regional pathological remodeling due to chronic coronary artery disease. It is not a valve disease but represents the valvular consequences of increased tethering forces and reduced closing forces. IMR is defined as mitral regurgitation caused by chronic changes of LV structure and function due to ischemic heart disease and it worsens the prognosis. In this review, we discuss on etiology, pathophysiology, and mechanisms of IMR, its classification, evaluation, and therapeutic corrective methods of IMR.

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Impact on sleep and mood in infants and mothers

Establishment of a consistent bedtime routine is often recommended to families with young children with sleep difficulties. However, there are limited studies assessing specific bedtime routines in the treatment of infant and toddler sleep disturbances. Thus, the purpose of this study was to examine the impact of a massage-based bedtime routine on infant sleep, maternal sleep, and maternal mood. 123 mothers and their 3- to 18-month-old infant were randomly assigned to a routine (1-week baseline of usual bedtime routine, 2-weeks intervention) or control group (3-weeks of their usual bedtime routine).

http://ift.tt/2y5zVIV

A standardized test to document cataplexy

/Background: Cataplexy is the pathognomonic symptom of narcolepsy type 1 (NT1). Since it is considered difficult to be directly observed or documented by clinicians, its diagnosis relies mainly on history taking. Our study aimed at testing the feasibility of a standardized video recording procedure under emotional stimulation to document cataplexy in the diagnostic work-up of suspected hypersomnia of central origin.

http://ift.tt/2gqCZFo

Actigraphy: A useful tool to monitor sleep-related hypermotor seizures

Sleep-related hypermotor epilepsy (SHE) is a rare form of focal epilepsy characterized by repeated episodes of vigorous hyperkinetic limb movements commonly confined to sleep. Seizures are highly stereotyped within patients and usually last less than two minutes.1 Wrist-actigraphy is commonly used to estimate the sleep-waking rhythm.2 Limb accelerometer sensors have been occasionally used for the detection of epileptic events during sleep,3-6 but routine wrist-actigraphy has not been described in SHE.

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Clinical significance of periodic limb movements during sleep: The HypnoLaus study

Periodic limb movements during sleep (PLMS) are prevalent in the general population, but their impact on sleep and association with cardiometabolic disorders are a matter of debate.

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Identifying the Best Sleep Measure to Screen Clinical Insomnia in a Psychiatric Population

Insomnia symptoms are highly prevalent among patients with psychiatric disorders and this mandates the need to identify the best self-administered sleep measure to screen for insomnia disorder among them.

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Short sleep and risk of proteinuria in 3-year-olds in Japan: A population-based cohort study

To examine whether short sleep at 18 months of age is associated with risk of proteinuria at 3 years of age.

http://ift.tt/2gpBOpZ

Revision repair of type IV laryngotracheoesophageal cleft using multiple long tapered engaging grafts

An 8 year-old female with esophageal atresia and a type IV laryngotracheoesophageal cleft underwent tracheostomy, gastric pull-up and fundoplication with G-tube insertion at birth. She remained nil per os due to aspiration. The trachealis was separated from the esophagus that was reapproximated and clavicular periosteum was placed. A long posterior costal cartilage graft that engaged behind the cricoid plate and tapered inferiorly was inserted. A second thin cartilage graft was sutured to it distally to extend the length of the repair.

http://ift.tt/2fWZyAU

Intrasinusal locking technique: a novel use of the ring block technique at sinus perforations for simultaneous implant placement

Ten patients who underwent sinus lift surgery with simultaneous implant placement using the intrasinusal locking technique were evaluated retrospectively. All patients were scheduled for sinus floor elevation procedures with simultaneous implant placement. Schneiderian membrane perforation occurred during the lifting procedure, and conventional methods failed to repair the perforation. Therefore, an autogenous bone ring was placed at the base of the maxillary sinus and was locked to the alveolar crest with a dental implant.

http://ift.tt/2kAJnyt

SPECT bone scintigraphy for the assessment of condylar growth activity in mandibular asymmetry: is it accurate?

The comparison of serial radiographs and clinical photographs is considered the current accepted standard for the diagnosis of active condylar hyperplasia in patients with facial asymmetry. Single photon emission computed tomography (SPECT) has recently been proposed as an alternative method. SPECT can be interpreted using three reported methods absolute difference in uptake, uptake ratio, and relative uptake. SPECT findings were compared to those from serial comparisons of radiographs and clinical photographs taken at the time of SPECT and a year later; the sensitivities and specificities were determined.

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Late-occurring nivolumab-induced cryptogenic organising pneumonia mimicking lung progression in a patient with metastatic non–small cell lung cancer

Publication date: November 2017
Source:European Journal of Cancer, Volume 85
Author(s): Linda Mahjoubi, Anas Gazzah, Aurélien Marabelle, François Le Roy Ladurie, Olivier Lambotte, Caroline Caramella, Julien Adam, Benjamin Besse, Jean-Charles Soria




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A systematic review of economic evaluation in pancreatic ductal adenocarcinoma

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Claire Gérard, Philippe Fagnoni, Angélique Vienot, Christophe Borg, Samuel Limat, Franck Daval, François Calais, Julie Vardanega, Marine Jary, Virginie Nerich
ObjectivesThe economic evaluation (EE) of healthcare interventions has become a necessity. However, high quality needs to be ensured in order to achieve validated results and help making informed decisions. Thus, the objective of the present study was to systematically identify and review published pancreatic ductal adenocarcinoma-related EEs and to assess their quality.MethodsSystematic literature research was conducted in PubMed and Cochrane to identify published EEs between 2000 and 2015. The quality of each selected EE was assessed by two independent reviewers, using the Drummond's checklist.ResultsOur systematic review was based on 32 EEs and showed a wide variety of methodological approaches, including different perspectives, time horizon, and cost effectiveness analyses. Nearly two-thirds of EEs are full EEs (n = 21), and about one-third of EEs had a Drummond score ≥7, synonymous with 'high quality'. Close to 50% of full EEs had a Drummond score ≥7, whereas all of partial EEs had a Drummond score <7 (n = 11).ConclusionsOver the past 15 years, a lot of interest has been evinced over the EE of pancreatic ductal adenocarcinoma (PDAC) and its direct impact on therapeutic advances in PDAC. To provide a framework for health care decision-making, to facilitate transferability and to lend credibility to health EEs, their quality must be improved. For the last 4 years, a tendency towards a quality improvement of these studies has been observed, probably coupled with a context of rational decision-making in health care, a better and wider spread of recommendations and thus, medical practitioners' full endorsement.



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Accuracy of screening women at familial risk of breast cancer without a known gene mutation: Individual patient data meta-analysis

Publication date: November 2017
Source:European Journal of Cancer, Volume 85
Author(s): Xuan-Anh Phi, Nehmat Houssami, Maartje J. Hooning, Christopher C. Riedl, Martin O. Leach, Francesco Sardanelli, Ellen Warner, Isabelle Trop, Sepideh Saadatmand, Madeleine M.A. Tilanus-Linthorst, Thomas H. Helbich, Edwin R. van den Heuvel, Harry J. de Koning, Inge-Marie Obdeijn, Geertruida H. de Bock
IntroductionWomen with a strong family history of breast cancer (BC) and without a known gene mutation have an increased risk of developing BC. We aimed to investigate the accuracy of screening using annual mammography with or without magnetic resonance imaging (MRI) for these women outside the general population screening program.MethodsAn individual patient data (IPD) meta-analysis was conducted using IPD from six prospective screening trials that had included women at increased risk for BC: only women with a strong familial risk for BC and without a known gene mutation were included in this analysis. A generalised linear mixed model was applied to estimate and compare screening accuracy (sensitivity, specificity and predictive values) for annual mammography with or without MRI.ResultsThere were 2226 women (median age: 41 years, interquartile range 35–47) with 7478 woman-years of follow-up, with a BC rate of 12 (95% confidence interval 9.3–14) in 1000 woman-years. Mammography screening had a sensitivity of 55% (standard error of mean [SE] 7.0) and a specificity of 94% (SE 1.3). Screening with MRI alone had a sensitivity of 89% (SE 4.6) and a specificity of 83% (SE 2.8). Adding MRI to mammography increased sensitivity to 98% (SE 1.8, P < 0.01 compared to mammography alone) but lowered specificity to 79% (SE 2.7, P < 0.01 compared with mammography alone).ConclusionIn this population of women with strong familial BC risk but without a known gene mutation, in whom BC incidence was high both before and after age 50, adding MRI to mammography substantially increased screening sensitivity but also decreased its specificity.



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The tenting technique: A novel filler technique in the danger zones

http://ift.tt/2ycj4nl

The 'Y' technique: An attempt to standardize nail dressing

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Clinical and dermoscopic characterization of pediatric and childhood melanomas. Multicenter study of 52 cases

Knowledge regarding the morphologic spectrum of pediatric melanoma (PM) is sparse and this may in part contribute to delay in detection and thicker tumors.

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Trends in US dermatology residency and fellowship programs and positions, 2006 to 2016

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87th Annual Meeting of the American Thyroid Association October 18–22, 2017, Victoria, British Columbia, Canada

Angela M. Leung and Mingzhao Xing
2017 ATA Annual Meeting Co-Chairs.

 We are excited that the 87th annual meeting of the American Thyroid Association (ATA) is almost upon us! On behalf of the Program Committee, we look forward to welcoming attendees and their guests to the annual meeting that will be held October 18–22, 2017, at the Fairmont Empress and Victoria Conference Centre in Victoria, British Columbia, Canada. Over this past year, the committee, comprised of experts from all thyroid disciplines, has thoughtfully worked to put together a program featuring the latest advances in basic, translational, and clinical thyroidology. Read More….

The post 87th Annual Meeting of the American Thyroid Association October 18–22, 2017, Victoria, British Columbia, Canada appeared first on American Thyroid Association.

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87th Annual Meeting of the American Thyroid Association October 18–22, 2017, Victoria, British Columbia, Canada

Angela M. Leung and Mingzhao Xing
2017 ATA Annual Meeting Co-Chairs.

 We are excited that the 87th annual meeting of the American Thyroid Association (ATA) is almost upon us! On behalf of the Program Committee, we look forward to welcoming attendees and their guests to the annual meeting that will be held October 18–22, 2017, at the Fairmont Empress and Victoria Conference Centre in Victoria, British Columbia, Canada. Over this past year, the committee, comprised of experts from all thyroid disciplines, has thoughtfully worked to put together a program featuring the latest advances in basic, translational, and clinical thyroidology. Read More….

The post 87th Annual Meeting of the American Thyroid Association October 18–22, 2017, Victoria, British Columbia, Canada appeared first on American Thyroid Association.

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Cardiac pathologic findings in three unusual cases of sudden cardiac death related to anorexiant drugs

Publication date: Available online 9 October 2017
Source:Human Pathology
Author(s): Ornella Leone, Valentina Agostini, Alberto Foà, Bruna Cerbelli, Cira Rosaria Tiziana di Gioia, Mariarosaria Aromatario, Costantino Ciallella, Joaquin Lucena, Giulia d'Amati
Amphetamine congeners can be prescribed as anorexiant drugs, despite their potential side effects, including cardiac toxicity. However, the morphologic features of cardiac damage related to protracted use of these compounds are unknown. We provide a detailed description of cardiac autopsy findings in three cases of sudden death associated with protracted use of high-doses of phendimetrazine and/or phenylpropanolamine or bupropion prescribed as anorexiants, in association with other compounds. The main cardiac findings were similar in all three cases: i) mild–moderate hypertrophy of the left ventricle and/or the septum; ii) myocardial non-ischemic scarring (mid-mural and/or sub-epicardial) appearing as discrete foci or with a band/like morphology; iii) mild–moderate intramural small vessel disease, in absence of significant epicardial coronary artery stenosis; iv) acute/recent inflammatory lesions consistent with toxic myocarditis. In summary, the detailed pathology examination of the heart in these three cases revealed myocardial lesions identical to those reported in catecholamine myocardial damage, in all their various stages of evolution. In presence of a clinical history of long-term intake of anorexiants of this category, it is most important at autopsy to recognize and correctly interpret the acute and chronic myocardial lesions of the type herein described, since they represent an anatomical substrate for arrhythmic death.



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Calcium channel blockers for lung function improvement in asthma

For decades, calcium channel blockers (CCBs) have been believed to play a role in asthma treatment. However, the clinical efficacy of CCBs for lung function improvement in patients with asthma has not been qualitatively evaluated.

http://ift.tt/2wJYW8K

Calcium channel blockers for lung function improvement in asthma

For decades, calcium channel blockers (CCBs) have been believed to play a role in asthma treatment. However, the clinical efficacy of CCBs for lung function improvement in patients with asthma has not been qualitatively evaluated.

http://ift.tt/2wJYW8K

Calf hemodialysate hypothesis: Nutritive value plus placebo effect

Publication date: November 2017
Source:Medical Hypotheses, Volume 109
Author(s): Sergei V. Jargin




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Reactions between methylglyoxal and its scavengers in-vivo appear to be catalyzed enzymatically

Publication date: Available online 9 October 2017
Source:Medical Hypotheses
Author(s): Benjamin Szwergold
Methylglyoxal (MGO) is an important contributor to the development of diabetic complications. In this paper I propose that MGO, not detoxified by the glyoxalase system, is removed from circulation by MGO-scavengers. Furthermore, since rates of reactions between MGO and its scavengers in-vitro are low, I propose that in-vivo these reactions are catalyzed enzymatically.



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M. biceps femoris - a wolf in sheep’s clothing: The downside of a lower limb injury prevention training

Publication date: Available online 9 October 2017
Source:Medical Hypotheses
Author(s): Thomas Ertelt, Thomas Gronwald
Both, hamstring and ACL injuries are amongst the most typical injuries, particularly in change of direction and high speed running sports. They're also difficult to treat. Therefore, in the past few years, sports medicine practitioners and exercise scientists have mainly been focusing on the de velopment and implementation of preventive programs in order to reduce the number of lower limb injuries, mainly by improving knee alignment. A number of studies have been able to prove the success of these training interventions, which are mainly addressing sensorimotor abilities and plyometric activities. The number of non‐contact hamstring injuries has nevertheless been on the rise, particularly in sports like soccer and football. Therefore, the purpose of the following article is to introduce the hypothesis that the above‐mentioned training interventions have a massive influence on the activation patterns on the targeted muscle group, and on the biceps femoris in particular. Muscle function and the resulting internal load are directly related to muscle architec ture at the insertion. Training induced adaptations in hamstring activation patterns can thus lead to an increased injury susceptibility. In this case, a simulation model that directly relates to an acute deceleration maneuver provides valuable insights into the function of the biceps femoris muscle, especially when the rate of activity and the muscle geometry at the insertion area are taken into consideration. We conclude that there needs to be a greater individualization of pre vention programs, especially in regards to anatomical requirements, in order to further reduce injury rates in elite sports. Moreover, it would also seem reasonable to apply a similar approach to aspects of chronic pain such as chronic non‐specific low back pain.



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