Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

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Πέμπτη 12 Νοεμβρίου 2020

Analysis of a Fractional Reaction-Diffusion HBV Model with Cure of Infected Cells

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In this paper, we propose a fractional reaction-diffusion model in order to better understand the mechanisms and dynamics of hepatitis B virus (HBV) infection in human body. The infection transmission is modeled by Hattaf–Yousfi functional response, and the fractional derivative is in the sense of Caputo. The global stability of the model equilibria is analyzed by means of Lyapunov functionals. Finally, numerical simulations are presented to support our analytical results.
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Using the Robson Classification to Explain the Fluctuations in Cesarean Section

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Purpose.tempspacetempspaceAs the rate of cesarean sections (CS) continues to rise in Flanders (northern part of Belgium), it is important to understand the reasons behind this evolution and to find ways to achieve appropriate CS rates.tempspacetempspaceFor this analysis, we categorized CS changes between 1992 and 2016, applying the Robson 10-Group Classification System (TGCS).tempspacetempspaceWe also applied the TGCS to analyze the information of the only clinics where between 2008 and 2016, the absolute CS rate had fallen by more than two percent.tempspacetempspaceMethods.tempspacetempspaceThis paper is based on a population-based cross-sectional study.tempspacetempspaceRobson's TGCS was used to analyze CS rates for the years 1992, 2000, 2008, and 2016, using the Flemish population-based birth register.temps pacetempspaceResults.tempspacetempspaceBetween 1992 and 2016, the overall CS rate increased from 11.8% in 1992 to 20.9% in 2016.tempspacetempspaceThe major contributors to that increase were (a) single, cephalic nulliparous women, at term in spontaneous labor (Robson group 1); (b) single, cephalic nulliparous women, at term in induced labor or CS before labor (group 2); and (c) multiparous women with single cephalic at term pregnancy with history of CS (group 5).tempspacetempspaceIn the subgroup of the seven clinics where the collective CS rate had decreased from 23.2% in 2008 to 19.3% in 2016, the main contributors to this decrease were Robson groups 1 and 2.tempspacetempspaceConclusions.tempspacetempspaceThe CS increase in Flanders between 1992 and 2016 is mainly the result of the absolute CS increase in the childbirth of nulliparous women with a single cephalic baby at term in spontaneous or induced labor and in women with a single cephalic presentation at term and a previous CS. tempspacetempspaceFurther research in these aforementioned groups is needed to identify the real reasons for the CS increase.
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Maternal Deaths due to Obstetric Haemorrhage in Dodoma Regional Referral Hospital, Tanzania

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Background.tempspacetempspaceDespite the availability of comprehensive emergency obstetric care at Dodoma Regional Referral Hospital, deaths due to obstetric haemorrhage are still high.tempspacetempspaceThis study was carried out to analyse the circumstances that had caused these deaths.tempspacetempspaceMethods.tempspacetempspaceA retrospective review of all files of women who had died of obstetric haemorrhage from January 2018 to December 2019 was made.tempspacetempspaceResults.tempspacetempspaceA total of 18,296 women gave birth at DRRH; out of these, 61 died of pregnancy-related complications of the deceased while 23 (38%) died of haemorrhage, with many of them 10 (44%) between the age of 30 and 34.tempspacetempspaceMany were grand multiparous women 8 (35%) and almost half of them (11 (48%)) had stayed at DRRH for less than 24 hours.tempspacetempspaceMore than half (12 (52%)) had delivered by caesarean section followed by laparotomy due to ruptured uterus (8 (35%)).tempspacetempspaceThe leading contributing factors to the deaths of these women were late referral (6 (26%)), delays in managing postpartum haemorrhage due to uterine atony (4 (17%)), inadequate preparations in patients with the possibility of developing PPH (4 (17%)), and delay in performing caesarean section (3 (13%)).tempspacetempspaceConclusion.tempspacetempspaceMaternal mortality due to obstetric haemorrhage is high at Dodoma Regional Referral Hospital where more than one-third of women died between 2018 and 2019.tempspacetempspaceAlmost all of these deaths were avoidable.tempspacetempspaceThe leading contributing factors were late referral from other health facilities, inadequate skills in managing PPH due to uterine atony, delays in performing caesarean section at DRRH, and inadequate preparation for managing PPH i n patients with abruptio placentae and IUFD which are risk factors for the condition.tempspacetempspaceThere is a need of conducting supportive supervision, mentorship, and other modes of teaching programmes on the management of obstetric haemorrhage to health care workers of referring facilities as well as those at DRRH.tempspacetempspaceMonitoring of labour by using partograph and identifying pregnant women at risk should also be emphasized in order to avoid uterine rupture.
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Can Mobile Technology Help Prevent the Burden of Dementia in Low- and Mid-Income Countries?

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Lifetime Duration of Exposure to Biomechanical Factors at Work as a Mediator of the Relationship Between Socioeconomic Position and Walking Speed

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The study aimed to assess the proportion mediated by the duration of exposure to ergonomic factors at work on the relationship between socioeconomic position (SEP) and low walking speed. This cross-sectional study was performed on data collected at baseline on 19,704 men and 20,273 women 45–70 years old, currently or previously employed, enrolled in the Constances cohort. SEP was assigned through current or last occupation, categorized in three classes, based on the European Socioeconomic Classification. W alking speed was assessed through one measurement of normal walking for 3 m and dichotomized at the lowest quintile of the sex- and age- (5-year) specific distribution. Self-reported workplace exposure throughout working life to repetitive work, intense physical work, and lifting/carrying heavy loads was used to assess the duration of exposure to each factor, categorized in four classes. Through Poisson regression models, adjusted for BMI, smoking, alcohol intake, hypertension, physical activity, diabetes, cardiovascular diseases, and a cognitive score, the attenuation in the prevalence ratio (PR) of low walking speed by SEP produced by the inclusion of duration of exposure to each factor was evaluated. The mediating effect of work ergonomic exposures on the relationship between SEP and low walking speed was assessed using the weighted method by Vanderweele. In the fully adjusted model without ergonomic exposures, both men and women in the middle and the lowest SEP had a significant ly increased risk of low walking speed compared with those in the highest SEP (men: PR = 1.30 and PR = 1.46, respectively; women: PR = 1.24 and PR = 1.45, respectively). The inclusion in separate regression models of exposure duration to repetitive work, intense physical work, and handling of heavy loads produced modest risk attenuations in both men and women, all smaller or around 10%. Mediation analysis revealed in both sexes significant mediation effects for most ergonomic exposures considered, although also with low mediation effects. Significant differences in walking speed by SEP were observed in this large sample, but the proportion of such differences explained by the duration of exposure to ergonomic factors at work was low using either the risk attenuation or the mediation analysis methods.

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Genome‐wide search for genes affecting the age at diagnosis of type 1 diabetes

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Genome‐wide search for genes affecting the age at diagnosis of type 1 diabetes


Abstract

Background

Type 1 diabetes (T1D) is an autoimmune disease affecting individuals in the early years of life. Although previous studies have identified genetic loci influencing T1D diagnosis age, these studies did not investigate the genome with high resolution.

Objective and methods

We performed a genome‐wide meta‐analysis for age at diagnosis with cohorts from Finland (Finnish Diabetic Nephropathy Study), the United Kingdom (UK Genetic Resource Investigating Diabetes) and Sardinia. Through SNP associations, transcriptome‐wide association analysis linked T1D diagnosis age and gene expression.

Results

We identified two chromosomal regions associated with T1D diagnosis age: multiple independent variants in the HLA region on chromosome 6 and a locus on chromosome 17q12. We performed gene‐level association tests with transcriptome prediction models from two whole blood datasets, lymphocyte cell line, spleen, pancreas and small intestine tissues. Of the non‐HLA genes, lower PNMT expression in whole blood, and higher IKZF3 and ZPBP2, and lower ORMDL3 and GSDMB transcription levels in multiple tissues were associated with lower T1D diagnosis age (FDR = 0.05). These genes lie on chr17q12 which is associated with T1D, other autoimmune diseases, and childhood asthma. Additionally, higher expression of PHF20L1, a gene not previously implicated in T1D, was associated with lower diagnosis age in lymphocytes, pancreas, and spleen. Altogether, the non‐HLA associations were enriched in open chromatin in various blood cells, blood vesse l tissues and foetal thymus tissue.

Conclusion

Multiple genes on chr17q12 and PHF20L1 on chr8 were associated with T1D diagnosis age and only further studies may elucidate the role of these genes for immunity and T1D onset.

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Application of spectral CT in the diagnosis of contrast encephalopathy following carotid artery stenting: a case report

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Abstract

Background

Contrast encephalopathy is a rare complication of carotid artery stenting (CAS). Contrast encephalopathy is a diagnosis of exclusion that often needs to be distinguished from high perfusion syndrome, cerebral haemorrhage, subarachnoid haemorrhage (SAH), cerebral infarction and so on.

Case presentation

In this study, we report on a 70-year-old man who was admitted to the hospital with transient ischaemic attacks presenting paroxysmal weakness of limbs in the previous 2 years. He had severe stenosis of the left internal carotid artery diagnosed by digital subtraction angiography (DSA) and underwent CAS. Two hours after the operation, the patient developed paralysis of the right upper limb, unclear speech, fever and restlessness. Emergency skull computed tomography (CT) showed swelling and a linear high-density area in the left cerebral hemisphere. To clarify the components of this high-density area in the traditional CT, the patient had spectral CT, which made the diagnosis of the leakage of contrast clear. After 1 week of supportive treatment, the patient improved.

Conclusions

Spectral CT can easily distinguish the components of high-density areas on traditional CT, which is haemorrhage, calcification or iodine contrast leakage. Therefore, spectral CT is worth consideration for the differential diagnosis of complications of vascular intervention.

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Vaccines, Vol. 8, Pages 673: SARS-CoV-2 Proteins Induce IFNG in Th1 Lymphocytes Generated from CD4+ Cells from Healthy, Unexposed Polish Donors

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Vaccines, Vol. 8, Pages 673: SARS-CoV-2 Proteins Induce IFNG in Th1 Lymphocytes Generated from CD4+ Cells from Healthy, Unexposed Polish Donors

Vaccines doi: 10.3390/vaccines8040673

Authors: Anna Sałkowska Iwona Karwaciak Kaja Karaś Jarosław Dastych Marcin Ratajewski

The outbreak of the SARS-CoV-2 virus in December 2019 has caused the deaths of several hundred thousand people worldwide. Currently, the pathogenesis of COVID-19 is poorly understood. During the course of COVID-19 infection, many patients experience deterioration, which might be associated with systemic inflammation and cytokine storm syndrome; however, other patients have mild symptoms or are asymptomatic. There are some suggestions that impaired cellular immunity through a reduction in Th1 response and IFNG (interferon gamma) expression, as well as cross-reactivity with common cold coronaviruses, might be involved in the differential COVID-19 course. Here, we show that CD4+ cells isolated from unexposed healthy donors that were differentiated towards the Th1 lineage in the presence of SARS-CoV-2 proteins exhibited induction of IFNG. Interestingly, the same cells induced to differentiate towards a Th17 lineage did not exhibit changes in IFNG expression or Th17-related cytokines. This suggests the cellular response to SARS-CoV-2 viral proteins is primarily associated with Th1 lymphocytes and may be dependent on past infections with common cold coronaviruses or vaccinations that induce unspecific cellular responses, e.g., BCG (Bacillus Calmette-Guérin). Thus, our results might explain the high variability in the course of COVID-19 among populations of different countries.

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Metastatic Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Current Treatment Standards and Future Perspectives

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Background: The basis of improved systemic therapy for inoperable or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer is formed by HER2-targeting monoclonal antibodies. Dual HER2 blockade with pertuzumab and trastuzumab in combination with docetaxel in previously untreated patients, and trastuzumab emtansine (T-DM1, an antibody-drug conjugate [ADC] consisting of trastuzumab, a linker and a cytotoxic payload) after prior trastuzumab therapy have demonstrated progression-free survival (PFS) and overall survival (OS) superior to what was achieved with the previous treatment routine. Therefore, pertuzumab and trastuzumab with chemotherapy (preferably with a taxane) and T-DM1 are considered the current standard of care in the first- and second-line settings, respectively. For later lines of therapy, no uniformly recognized standard of care has been defined. Accepted options include treatment with trastuzumab beyond progression, in combi nation with a broad variety of single-agent chemotherapies used sequentially, or lapatinib (an HER2-targeting tyrosine kinase inhibitor [TKI]) in combination with either trastuzu­mab or capecitabine. However, most of these options have not been formally tested in patients receiving the current standard of care therapy for metastatic disease. Summary: In patients previously treated with today's standard of care, including a significant subgroup with untreated or progressing brain metastases, the combination of tucatinib, a novel HER2-targeting TKI, with trastuzumab and capecitabine, demonstrates a clinically meaningful improvement in PFS and OS when compared to placebo with trastuzumab and capecitabine. Neratinib, another HER2 TKI, in combination with capecitabine, compared to lapatinib and capecitabine, as well as margetuximab, an HER2-directed monoclonal antibody with a fragment c (Fc) domain engineered to enhance immune activation, compared to trastuzumab, both co mbined with the investigator's choice of chemotherapy, showed a statistically significantly longer PFS. However, not all patients in the respective trials had received pertuzumab and T-DM1 prior to enrollment and, so far, no improvement in OS has been demonstrated. After a median of 6 prior lines of therapy, trastuzumab deruxtecan (T-DXd), a novel ADC, showed a meaningful overall response and PFS. Although the safety profile was generally manageable, treatment-related interstitial lung disease (ILD) might pose a challenge in routine practice. Pyrotinib, another HER2 TKI, was evaluated in combination with capecitabine in patients after prior exposure to trastuzumab when pertuzumab and T-DM1 were not available. In this setting, PFS was better than with lapatinib and capecitabine. Key Messages: In 2020, pertuzumab and trastuzumab with taxane-based chemotherapy in the first line, and T-DM1 in the second line, remain the standard of care. Tucatinib, neratinib, margetuxima b, and T-DXd expand the armamentarium for treatment beyond the second line. Pyrotinib might be another option, especially for patients, who do not have access to pertuzumab and T-DM1.
Breast Care
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Vaccines, Vol. 8, Pages 674: The Impact of Serotype Cross-Protection on Vaccine Trials: DENVax as a Case Study

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Vaccines, Vol. 8, Pages 674: The Impact of Serotype Cross-Protection on Vaccine Trials: DENVax as a Case Study

Vaccines doi: 10.3390/vaccines8040674

Authors: Maíra Aguiar Nico Stollenwerk

There is a growing public health need for effective preventive interventions against dengue, and a safe, effective and affordable dengue vaccine against the four serotypes would be a significant achievement for disease prevention and control. Two tetravalent dengue vaccines, Dengvaxia (CYD-TDV—Sanofi Pasteur) and DENVax (TAK 003—Takeda Pharmaceutical Company), have now completed phase 3 clinical trials. Although Dengvaxia resulted in serious adverse events and had to be restricted to individuals with prior dengue infections, DENVax has shown, at first glance, some encouraging results. Using the available data for the TAK 003 trial, we estimate, via the Bayesian approach, vaccine efficacy (VE) of the post-vaccination surveillance periods of 12 and 18 months. Although better measurement over a long time was expected for the second part of the post-vaccination surveillance, variation in serotype-specific efficacy needs careful consideration. Besides observing tha t individual serostatus prior to vaccination is determinant of DENVax vaccine efficacy, such as for Dengvaxia, we also noted, after comparing the VE estimations for 12- and 18-month periods, that vaccine efficacy is decreasing over time. The comparison of efficacies over time is informative and very important, and brings up the discussion of the role of temporary cross-immunity in dengue vaccine trials and the impact of serostatus prior to vaccination in the context of dengue fever epidemiology.

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Validation of a Modified CDC Assay and Performance Comparison with the NeuMoDx™ and DiaSorin® automated assays for Rapid Detection of SARS-CoV-2 in Respiratory Specimens

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Publication date: Available online 11 November 2020

Source: Journal of Clinical Virology

Author(s): Amorce Lima, Vicki Healer, Elaine Vendrone, Suzane Silbert

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Vaccines, Vol. 8, Pages 675: Association between Exposure to Influenza Vaccination and COVID-19 Diagnosis and Outcomes

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Vaccines, Vol. 8, Pages 675: Association between Exposure to Influenza Vaccination and COVID-19 Diagnosis and Outcomes

Vaccines doi: 10.3390/vaccines8040675

Authors: Pietro Ragni Massimiliano Marino Debora Formisano Eufemia Bisaccia Stefania Scaltriti Emanuela Bedeschi Roberto Grilli

We explored whether influenza vaccination (IV) affects susceptibility to SARS-CoV-2 infection and clinical outcomes in COVID-19 patients in 17,608 residents of the Italian province of Reggio Emilia undergoing a SARS-CoV-2 test. Exposure to IV was ascertained and the strength of the association with SARS-CoV-2 positivity expressed with odds ratios (OR). Rates of hospitalisations and death in those found positive were assessed and hazard ratios (HR) were estimated. The prevalence of IV was 34.3% in the 4885 SARS-CoV-2 positive and 29.5% in the 12,723 negative subjects, but the adjusted OR indicated that vaccinated individuals had a lower probability of testing positive (OR = 0.89; 95% CI 0.80–0.99). Among the 4885 positive individuals, 1676 had received IV. After adjusting for confounding factors, there was no association between IV and hospitalisation (1.00; 95% CI 0.84–1.29) or death (HR = 1.14; 95% CI 0.95–1.37). However, for patients age ≥65 vaccinated close to the SARS-CoV-2 outbreak, HRs were 0.66 (95% CI: 0.44–0.98) and 0.70 (95% CI 0.50–1.00), for hospitalisation and death, respectively. In this study, IV was associated with a lower probability of COVID-19 diagnosis. In COVID-19 patients, overall, IV did not affect outcomes, although a protective effect was observed for the elderly receiving IV almost in parallel with the SARS-CoV-2 outbreak. These findings provide reassurance in planning IV campaigns and underscore the need for exploring further their impact on COVID-19.

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