Membrane binding and lipid-protein interaction of the C2 domain from coagulation factor V.

Anchoring of coagulation factors to anionic regions of the membrane involves the C2 domain as a key player. The rate of enzymatic reactions of the coagulation factors is increased by several orders of magnitude upon membrane binding. However, the precise mechanisms behind the rate acceleration remain unclear, primarily because of a lack of understanding of the conformational dynamics of the C2-containing factors and corresponding complexes. We elucidate the membrane-bound form of the C2 domain from human coagulation factor V (FV-C2) by characterizing its membrane binding the specific lipid-protein interactions. Employing all-atom molecular dynamics simulations and leveraging the highly mobile membrane-mimetic (HMMM) model, we observed spontaneous binding of FV-C2 to a phosphatidylserine (PS)-containing membrane within 2-25 ns across twelve independent simulations. FV-C2 interacted with the membrane through three loops (spikes 1-3), achieving a converged, stable orientation. Multiple HMMM trajectories of the spontaneous membrane binding provided extensive sampling and ample data to examine the membrane-induced effects on the conformational dynamics of C2 as well as specific lipid-protein interactions. Despite existing crystal structures representing presumed "open" and "closed" states of FV-C2, our results revealed a continuous distribution of structures between these states, with the most populated structures differing from both "open" and "closed" states observed in crystal environments. Lastly, we characterized a putative PS-specific binding site formed by K23, Q48, and S78 located in the groove enclosed by spikes 1-3 (PS-specificity pocket), suggesting a different orientation of a bound headgroup moiety compared to previous proposals based upon analysis of static crystal structures.

Enhancing predictability of IDH mutation status in glioma patients at initial diagnosis: a comparative analysis of radiomics from MRI, [18F]FET PET, and TSPO PET.

PURPOSE: According to the World Health Organization classification for tumors of the central nervous system, mutation status of the isocitrate dehydrogenase (IDH) genes has become a major diagnostic discriminator for gliomas. Therefore, imaging-based prediction of IDH mutation status is of high interest for individual patient management. We compared and evaluated the diagnostic value of radiomics derived from dual positron emission tomography (PET) and magnetic resonance imaging (MRI) data to predict the IDH mutation status non-invasively. METHODS: Eighty-seven glioma patients at initial diagnosis who underwent PET targeting the translocator protein (TSPO) using [18F]GE-180, dynamic amino acid PET using [18F]FET, and T1-/T2-weighted MRI scans were examined. In addition to calculating tumor-to-background ratio (TBR) images for all modalities, parametric images quantifying dynamic [18F]FET PET information were generated. Radiomic features were extracted from TBR and parametric images. The area under the receiver operating characteristic curve (AUC) was employed to assess the performance of logistic regression (LR) classifiers. To report robust estimates, nested cross-validation with five folds and 50 repeats was applied. RESULTS: TBRGE-180 features extracted from TSPO-positive volumes had the highest predictive power among TBR images (AUC 0.88, with age as co-factor 0.94). Dynamic [18F]FET PET reached a similarly high performance (0.94, with age 0.96). The highest LR coefficients in multimodal analyses included TBRGE-180 features, parameters from kinetic and early static [18F]FET PET images, age, and the features from TBRT2 images such as the kurtosis (0.97). CONCLUSION: The findings suggest that incorporating TBRGE-180 features along with kinetic information from dynamic [18F]FET PET, kurtosis from TBRT2, and age can yield very high predictability of IDH mutation status, thus potentially improving early patient management.

Allelic strengths of encephalopathy-associated UBA5 variants correlate between in vivo and in vitro assays.

Protein UFMylation downstream of the E1 enzyme UBA5 plays essential roles in development and endoplasmic reticulum stress. Variants in the UBA5 gene are associated with developmental and epileptic encephalopathy 44 (DEE44), an autosomal recessive disorder characterized by early-onset encephalopathy, movement abnormalities, global developmental delay, intellectual disability, and seizures. DEE44 is caused by at least 12 different missense variants described as loss of function (LoF), but the relationships between genotypes and molecular or clinical phenotypes remain to be established. We developed a humanized UBA5 fly model and biochemical activity assays in order to describe in vivo and in vitro genotype-phenotype relationships across the UBA5 allelic series. In vivo, we observed a broad spectrum of phenotypes in viability, developmental timing, lifespan, locomotor activity, and bang sensitivity. A range of functional effects was also observed in vitro across comprehensive biochemical assays for protein stability, ATP binding, UFM1 activation, and UFM1 transthiolation. Importantly, there is a strong correlation between in vivo and in vitro phenotypes, establishing a classification of LoF variants into mild, intermediate, and severe allelic strengths. By systemically evaluating UBA5 variants across in vivo and in vitro platforms, this study provides a foundation for more basic and translational UBA5 research, as well as a basis for evaluating current and future individuals afflicted with this rare disease.

Although rare diseases only impact a small fraction of the population, they still affect hundreds of millions of people around the world. Many of these conditions are caused by variations in inherited genetic material, which nowadays can be readily detected using advanced sequencing technologies. However, establishing a connection between these genetic changes and the disease they cause often requires further in-depth study. One such rare inherited disorder is developmental and epileptic encephalopathy type 44 (DEE44), which is caused by genetic variations within the gene for UBA5 (short for ubiquitin-like modifier activating enzyme 5). For DEE44 to occur, both copies of the gene for UBA5, known as alleles, must contain one or more detrimental variation. Although all these variations prevent UBA5 from working correctly, the level of disruption they cause, known as allelic strength, varies between them. However, it remained unclear whether the severity of the DEE44 disease directly corresponds with the allelic strength of these variants. To answer this question, Pan et al. tested how different genetic variants found in patients with DEE44 affected the behavior and health of fruit flies. These results were then compared against in vitro biochemical assays testing how alleles containing these variants impacted the function of UBA5. When the fly gene for the enzyme was replaced with the human gene containing variations associated with DEE44, flies exhibited changes in their survival rates, developmental progress, lifespan, and neurological well-being. However, not all of the variants caused ill effects. Using this information, the patient variants were classified into three categories based on the severity of their effect: mild, intermediate, and severe. Biochemical assays supported this classification and revealed that the variants that caused more severe symptoms tended to inhibit the activity of UBA5 more significantly. Pan et al. further analyzed the nature of the variants in the patients and showed that most patients typically carried one mild and one strong variant, although some individuals did have two intermediate variants. Notably, no patients carried two severe variants. This indicates that DEE44 is the result of UBA5 only partially losing its ability to work correctly. The study by Pan et al. provides a framework for assessing the impact of genetic variants associated with DEE44, aiding the diagnosis and treatment of the disorder. However, further research involving more patients, more detailed clinical data, and testing other newly identified DEE44-causing variants is needed to solidify the correlation between allelic strength and disease severity.

On choosing the vehicles of metaphors 2.0: the interactive effects of semantic neighborhood density and body-object interaction on metaphor production.

In a metaphor, such as language is a bridge, two distinct concepts known as the topic (i.e., language) and vehicle (i.e., bridge) are juxtaposed to produce figurative meaning. Previous work demonstrated that, when creating metaphors, participants choose vehicles that are concrete, rather than abstract, and are also a moderate semantic distance away from the topic. However, little is known about the semantic representations underlying metaphor production beyond topic-vehicle semantic distance and vehicle concreteness. Here, we studied the role of two semantic richness variables in metaphor production - semantic neighborhood density (SND), which measures the proximity of a word and its associations in semantic space, and body-object interaction (BOI), which reflects the ease with which a human body can motorically interact with a word's referent. In each trial, participants were presented with an abstract topic, such as miracle, and were instructed to make an apt and comprehensible metaphor by choosing a vehicle word (e.g., lighthouse). All of the topics were abstract but half were high-SND (from dense semantic neighborhoods) and half were low-SND (from sparse semantic neighborhoods). Similarly, half of the potential vehicle words were either high or low in SND and also differed on BOI such that half were high-BOI (e.g., bicycle), whereas half were low-BOI (e.g., rainbow). We observed a three-way interaction such that participants selected low-BOI, rather than high-BOI, vehicle words when topics or vehicles were high-SND. We interpret this finding to suggest that participants attempt to reduce the overall semantic richness of their created metaphors.

Allelic strengths of encephalopathy-associated UBA5 variants correlate between in vivo and in vitro assays.

Protein UFMylation downstream of the E1 enzyme UBA5 plays essential roles in development and ER stress. Variants in the UBA5 gene are associated with developmental and epileptic encephalopathy 44 (DEE44), an autosomal recessive disorder characterized by early-onset encephalopathy, movement abnormalities, global developmental delay, intellectual disability, and seizures. DEE44 is caused by at least twelve different missense variants described as loss of function (LoF), but the relationships between genotypes and molecular or clinical phenotypes remains to be established. We developed a humanized UBA5 fly model and biochemical activity assays in order to describe in vivo and in vitro genotype-phenotype relationships across the UBA5 allelic series. In vivo, we observed a broad spectrum of phenotypes in viability, developmental timing, lifespan, locomotor activity, and bang sensitivity. A range of functional effects was also observed in vitro across comprehensive biochemical assays for protein stability, ATP binding, UFM1 activation, and UFM1 transthiolation. Importantly, there is a strong correlation between in vivo and in vitro phenotypes, establishing a classification of LoF variants into mild, intermediate, and severe allelic strengths. By systemically evaluating UBA5 variants across in vivo and in vitro platforms, this study provides a foundation for more basic and translational UBA5 research, as well as a basis for evaluating current and future individuals afflicted with this rare disease.

Influence of the sickle cell trait on Plasmodium falciparum infectivity from naturally infected gametocyte carriers.

BACKGROUND: Sickle cell trait (SCT) refers to the carriage of one abnormal copy of the ß-globin gene, the HbS allele. SCT offers protection against malaria, controlling parasite density and preventing progression to symptomatic malaria. However, it remains unclear whether SCT also affects transmission stages and mosquito infection parameters. Deciphering the impact of the SCT on human to mosquito malaria transmission is key to understanding mechanisms that maintain the trait in malaria endemic areas. METHODS: The study was conducted from June to July 2017 among asymptomatic children living in the locality of Mfou, Cameroon. Blood samples were collected from asymptomatic children to perform malaria diagnosis by microscopy, Plasmodium species by PCR and hemoglobin typing by RFLP. Infectiousness of gametocytes to mosquitoes was assessed by membrane feeding assays using blood from gametocyte carriers of HbAA and HbAS genotypes. A zero-inflated model was fitted to predict distribution of oocysts in mosquitoes according to hemoglobin genotype of the gametocyte source. RESULTS: Among the 1557 children enrolled in the study, 314 (20.16%) were of the HbAS genotype. The prevalence of children with P. falciparum gametocytes was 18.47% in HbAS individuals and 13.57% in HbAA, and the difference is significant (χ2 = 4.61, P = 0.032). Multiplicity of infection was lower in HbAS gametocyte carriers (median = 2 genotypes/carrier in HbAS versus 3.5 genotypes/carrier in HbAA, Wilcoxon sum rank test = 188, P = 0.032). Gametocyte densities in the blood donor significantly influenced mosquito infection prevalence in both HbAS and HbAA individuals. The HbAS genotype had no significant effect on mosquito infection outcomes when using immune or naïve serum in feeding assays. In AB replacement feeding experiments, the odds ratio of mosquito infection for HbAA blood as compared to HbAS was 0.56 (95% CI 0.29-1.10), indicating a twice higher risk of infection in mosquitoes fed on gametocyte-containing blood of HbAS genotype. CONCLUSION: Plasmodium transmission stages were more prevalent in SCT individuals. This may reflect the parasite's enhanced investment in the sexual stage to increase their survival rate when asexual replication is impeded. The public health impact of our results points the need for intensive malaria control interventions in areas with high prevalence of HbAS. The similar infection parameters in feeding experiments where mosquitoes received the original serum from the blood donor indicated that immune responses to gametocyte surface proteins occur in both HbAS and HbAA individuals. The higher risk of infection in mosquitoes fed on HbAS blood depleted of immune factors suggests that changes in the membrane properties in HbAS erythrocytes may impact on the maturation process of gametocytes within circulating red blood cells.

COVID-19-Induced Redundancy and Socio-Psychological Well-Being of Tourism Employees: Implications for Organizational Recovery in a Resource-Scarce Context.

Drawing on social and psychological well-being literature underpinned by the concept of resilience, this study examines the impact of COVID-19 induced redundancy on the socio-psychological well-being of redundant employees (laid-off or working reduced hours), and its effect on their commitment to work and support recovery in the tourism industry. Utilizing a quantitative-dominant mixed methods design, 457 questionnaires were administered, and 15 interviews conducted with redundant employees in Ghana between May and August 2020. Results from a binary logistic regression analysis of the survey data supported by qualitative interview analysis indicate that marital status, education, status of dependents, and the types of tourism businesses employed in, significantly influenced psychological well-being while marital status, age, education, and rank in the organization influenced the social well-being of respondents. Meanwhile, psychological well-being significantly influenced future work commitment in the industry. Managerial implications for supporting employee resilience, well-being, and future recovery strategies are critically examined.

The CHALLENGE trial: the effects of a virtual reality-assisted exposure therapy for persistent auditory hallucinations versus supportive counselling in people with psychosis: study protocol for a randomised clinical trial.

BACKGROUND: Many patients suffering from schizophrenia spectrum disorders continue having distressing auditory hallucinations in spite of treatment with antipsychotic medication. The aim of this trial is to examine the effect of a targeted virtual reality therapy for persistent auditory hallucinations in individuals with psychosis. The trial explores whether this type of therapy can decrease the severity, frequency and distress of auditory hallucinations and, additionally, whether it can reduce clinical symptoms and enhance daily functioning in individuals with psychosis. METHODS: The study is a randomised, assessor-blinded parallel-group superiority clinical trial, allocating a total of 266 patients to either the experimental intervention or supportive counselling. The participants will be randomised to either (1) seven sessions of virtual reality therapy or (2) seven sessions of supportive counselling to be delivered within the first 12 weeks after inclusion in the study. All participants will be assessed at baseline and 12 and 24 weeks post-baseline. Independent assessors blinded to the treatment allocation will evaluate the outcome. The primary outcome is the level of auditory hallucinations measured with the Psychotic Symptoms Rating Scales (PSYRATS-AH) total score at the cessation of treatment at 12 weeks. Secondary outcomes are frequency of auditory hallucinations, the distress caused by auditory hallucinations, perceived voice power, patient acceptance of voices, patients' ability to respond to voices in an assertive way and social and daily function. DISCUSSION: Promising evidence of the efficacy of this immersive virtual reality-based therapy for auditory hallucinations exist, but evidence needs to be established in a large, methodological rigorous trial. If the therapy proves to be beneficial in reducing the severity of refractory auditory hallucinations, a large group of patients with schizophrenia and related disorders could be the target group of this short-term psychotherapeutic intervention.

Genetic Diversity of Plasmodium falciparum and Distribution of Antimalarial Drug Resistance Mutations in Symptomatic and Asymptomatic Infections.

Malaria control relies on passive case detection, and this strategy fails detecting asymptomatic infections. In addition, infections in endemic areas harbor multiple parasite genotypes that could affect case management and malaria epidemiology. Here, we performed AmpSeq genotyping to capture polymorphisms associated with antimalarial resistance and the genetic diversity within natural Plasmodium falciparum infections. Known genetic polymorphisms associated with altered drug susceptibility were screened for the five most common marker genes, pfdhfr, pfdhps, pfmdr1, pfcrt, and pfK13, and genetic diversity was established from two known AmpSeq markers, cpmp and csp. Relative abundance of the different genotypes within mixed infections was calculated from the number of reads per genotype. Genotyping was performed on 117 samples, 63 from asymptomatic and 54 from symptomatic individuals. We identified up to 15 genotypes within an infection, and the median multiplicity of infection was higher in asymptomatic infections (median MOI = 5 in asymptomatics versus median MOI = 2 in symptomatics, P < 0.001). No genetic differentiation on parasites from asymptomatic and symptomatic individuals was found. No mutation associated with ART resistance was identified. Prevalence of the P. falciparum chloroquine resistance wild-type genotype (CVMNK) reached 80%, confirming a return to chloroquine (CQ) sensitive parasites in Cameroon. In addition, the CQ-associated resistant genotype (CVIET) was present at very low density in polyclonal infections. Persistence of low-density chloroquine resistant parasites indicates competition-survival trade-offs may contribute to maintaining genetic diversity in natura. Thus, monitoring the expansion of these low-density genotypes in different immune backgrounds will be critical to evaluate drug policy changes.

Predictors of HIV Among 1 Million Clients in High-Risk Male Populations in Tanzania.

The World Health Organization identified men as an essential group to target with HIV testing and treatment strategies;: men who have sex with men (MSM) and male clients of female sex workers (CFSW) account for 35% of new HIV infections globally. Using a cross-sectional design from a community-based HIV prevention project in Tanzania (October 2015-September 2018) and multivariable logistic regression, we identified predictors of HIV seropositivity among men. Of 1,041,343 men on their initial visit to the project, 36,905 (3.5%) were MSM; 567,005 (54.5%) were CFSW; and 437,343 (42.0%) were other men living near hotspots (OMHA). Three predictors of HIV seropositivity emerged across all three groups: being uncircumcised, having sexually transmitted infection symptoms, and harmful drinking of alcohol before sex. Any reported form of gender-based violence among MSM and OMHA and inconsistent condom use among CFSW were associated with HIV seropositivity. These findings may inform community HIV strategies like self-testing, delivery of pre-exposure prophylaxis and antiretroviral therapy, and behavioral change communication targeting men at higher risk of infection.

MRI-based contrast clearance analysis shows high differentiation accuracy between radiation-induced reactions and progressive disease after cranial radiotherapy.

BACKGROUND: Pseudoprogression (PsP) or radiation necrosis (RN) may frequently occur after cranial radiotherapy and show a similar imaging pattern compared with progressive disease (PD). We aimed to evaluate the diagnostic accuracy of magnetic resonance imaging-based contrast clearance analysis (CCA) in this clinical setting. PATIENTS AND METHODS: Patients with equivocal imaging findings after cranial radiotherapy were consecutively included into this monocentric prospective study. CCA was carried out by software-based automated subtraction of imaging features in late versus early T1-weighted sequences after contrast agent application. Two experienced neuroradiologists evaluated CCA with respect to PsP/RN and PD being blinded for histological findings. The radiological assessment was compared with the histopathological results, and its accuracy was calculated statistically. RESULTS: A total of 33 patients were included; 16 (48.5%) were treated because of a primary brain tumor (BT), and 17 (51.1%) because of a secondary BT. In one patient, CCA was technically infeasible. The accuracy of CCA in predicting the histological result was 0.84 [95% confidence interval (CI) 0.67-0.95; one-sided P = 0.051; n = 32]. Sensitivity and specificity of CCA were 0.93 (95% CI 0.66-1.00) and 0.78 (95% CI 0.52-0.94), respectively. The accuracy in patients with secondary BTs was 0.94 (95% CI 0.71-1.00) and nonsignificantly higher compared with patients with primary BT with an accuracy of 0.73 (95% CI 0.45-0.92), P = 0.16. CONCLUSIONS: In this study, CCA was a highly accurate, easy, and helpful method for distinguishing PsP or RN from PD after cranial radiotherapy, especially in patients with secondary tumors after radiosurgical treatment.

Evaluation of the MGDRx eyebag treatment in young and older subjects with dry eye symptoms.

OBJECTIVES: This study aims to evaluate the relationship between application of the MGDRx thermal eyebag and dry eye signs and symptoms in young and older subjects and to compare the results between the two groups. METHODS: Thirty young, healthily volunteers between 18 and 31 years of age (23.95±3.94 years) and thirty older subjects between 61 and 90 years of age (77.97±8.11 years) participated in this study. Ocular surface parameters were assessed using the Oculus Keratograph 5M, following the guidelines of the Tear Film and Ocular Surface Dry Eye Workshop II Diagnostic Methodology report. Only subjects with a positive score on at least one questionnaire and an initial Non-Invasive Keratograph Break-Up Time (NIKBUT) under 10seconds were included in the study. After thermal bag self-application in both eyes every day for 2 weeks, the protocol was carried out again. Lid massage was performed after lid warming. Compliance and degree of improvement were also assessed. MAIN RESULTS: The young volunteer group showed an improvement in NIKBUT, lipid layer score, upper eyelid gland drop-out percentage and dry eye symptoms over the two week treatment period. Improvements in meibum quality, gland obstruction, telangiectasia scores, and dry eye symptoms were found in the older subjects. Mixed ANOVA revealed better NIKBUT and lipid layer values in the young subjects. Despite the treatment compliance being statistically higher in the older group than in the younger subjects (P=0.002), there were no significant differences in subjective improvement between groups (P=0.097). CONCLUSION: Dry eye-related symptoms were improved after thermal bag application, while NIKBUT and lipid layer thickness were improved only in the younger subjects.

Men's comfort in distributing or receiving HIV self-test kits from close male social network members in Dar Es Salaam, Tanzania: baseline results from the STEP project.

BACKGROUND: A variety of strategies have been used to reach men with HIV self-testing services, including social network-based HIV self-test kits distribution. However, few studies have assessed men's comfort to distribute to or receive HIV self-test kits from close male friends within the same social network. In this study, we assessed men's comfort to distribute to and/or receive HIV self-test kits from close male friends and associated factors among men who socialize in networks locally referred to as "camps" in Tanzania. METHODS: Data are from the baseline survey of a cluster-randomized controlled trial conducted in June 2019 with 18 social networks or "camps" in Dar es Salaam, Tanzania. Participants were 18-year-old or older male camp members who were HIV-negative at the time of enrolment. We used the Generalized Estimating Equations (GEE) to assess factors associated with being comfortable to distribute to and/or receive HIV self-test kits from close male members within one's social network. RESULTS: Of 505 participants, 67.9% (n = 342) reported being comfortable to distribute to while 68.2% (n = 344) were comfortable to receive HIV self-test kits from their close male friends. Ever having heard about HIV self-testing (Adjusted Prevalence Ratio (Adj. PR): 1.6; 95% Confidence Interval [CI]: 1.3, 1.9), willingness to self-test for HIV in front of a sexual partner (Adj. PR: 3.0; 95%CI: 1.5, 6.1) and exposure to peer-led HIV self-testing education and promotion (Adj. PR: 1.4; 95%CI: 1.2, 1.7) were significantly associated with being comfortable to distribute HIV self-test kits to close male members within one's social network. Similar results were observed for being comfortable to receive HIV self-test kits from a close male friend within one's social network. CONCLUSIONS: Overall, these findings suggest that distribution of HIV self-test kits through close male friends could improve the proportion of men reached with HIV self-testing services and improve HIV testing rates in this population where uptake remains low. However, additional promotional strategies such as peer-led HIV self-testing education are needed to raise awareness and increase the proportion of men who are comfortable to receive and/or distribute HIV self-testing kits.

Expression of Retroelements in Cervical Cancer and Their Interplay with HPV Infection and Host Gene Expression.

Retroelements are expressed in diverse types of cancer and are related to tumorigenesis and to cancer progression. We characterized the expression of retroelements in cervical cancer and explored their interplay with HPV infection and their association with expression of neighboring genes. Forty biopsies of invasive cervical carcinoma (squamous cell carcinomas and adenocarcinomas) with genotyped HPV were selected and analyzed for human endogenous retrovirus (HERV) and long interspersed nuclear element 1 (L1) expression through RNA-seq data. We found 8060 retroelements expressed in the samples and a negative correlation of DNA methyltransferase 1 expression with the two most expressed L1 elements. A total of 103 retroelements were found differentially expressed between tumor histological types and between HPV types, including several HERV families (HERV-K, HERV-H, HERV-E, HERV-I and HERV-L). The comparison between HPV mono- and co-infections showed the highest proportion of differentially expressed L1 elements. The location of retroelements affected neighboring gene expression, such as shown for the interleukin-20 gene family. Three HERVs and seven L1 were located close to this gene family and two L1 showed a positive association with IL20RB expression. This study describes the expression of retroelements in cervical cancer and shows their association with HPV status and host gene expression.

The psychology of saying what you don't mean: Celebrating the research career of Professor Albert Katz-A personal reflection.

Throughout his 45-year career, Professor Albert Katz (Department of Psychology, Western University) has tackled challeng ing aspects of human communication in a way that creatively merges the theoretical insights and empirical rigor of cognitive linguistics, psycholinguistics, and cognitive neuroscience. In this personal reflection, Professor Katz writes a short biographical piece on the life journey that led to his research programs. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Risk factors assessment in fibular free flap mandibular reconstruction.

INTRODUCTION: The fibular free flap (FFF) is the best choice method for mandibular reconstruction. However, the failure and the complications risk factors (RF) are not yet fully identified. This study aims to analyze these RF in order to improve the success rate. MATERIAL: This retrospective study includes all patients who benefited from a FFF mandibular reconstruction between the first of January, 2014 and the thirty-first of December, 2018 in the Department of Stomatology and Maxillofacial Surgery department of the CHU Saint-Pierre Hospital, Brussels, Belgium. RESULTS: Thirty patients benefited from this intervention. The overall success rate was 90%. Majority of the patients were men (67%) (mean age: 52 years). The main associated co-morbidities were: alcohol (50%), tobacco consumption (67%) and previous radiotherapy (20%). The mean operative time was 9,5hours. The morbidities rates at the receiving site (RS) and the donor site (DS) were respectively 43% and 30%. Infection and dehiscence of the RS were the main complications. Statistical analysis identified RF for RS infections: atherosclerosis and operative time; RS dehiscence (previous cervical dissection and secondary reconstruction); flap necrosis (ischemia time, rate of infection at the recipient site, history of radiation therapy, alcohol consumption, National Nosocomial Infection Surveillance score (NNISS), and history of cervical dissection); and DS morbidities (NNISS and dehiscence rate at the DS in the early period). CONCLUSION: The FFF mandibular reconstruction offers a significant success rate. Nevertheless, this study highlighted several failure and complications RF of the procedure. Previous neck dissection and radiotherapy, operative and the ischemia time, were RF associated with complication at the RS. Furthermore, the NNIS score and the dehiscence rate were also reported as RF for FFF necrosis.

Controlling the first wave of the COVID-19 pandemic in Malawi: results from a panel study

Many African countries have experienced a first wave of the COVID-19 pandemic between June and August of 2020. According to case counts reported daily by epidemiological surveillance systems, infection rates remained low in most countries. This defied early models of the potential impact of COVID-19 on the continent, that projected large outbreaks and massive strain on health systems. Theories proposed to explain the apparently limited spread of the novel coronavirus in most African countries have emphasized 1) early actions by health authorities (e.g., border closures) and 2) biological or environmental determinants of the transmissibility of SARS-CoV-2 (e.g., warm weather, cross-immunity). In this paper, we explored additional factors that might contribute to the low recorded burden of COVID-19 in Malawi, a low-income country in Southeastern Africa. To do so, we used 4 rounds of panel data collected among a sample of adults during the first 6 months of the pandemic in the country. Our analyses of survey data on SARS-CoV-2 testing and COVID-related symptoms indicate that the size of the outbreak that occurred in June-August 2020 might be larger than recorded by surveillance systems that rely on RT-PCR testing. Our data also document the widespread adoption of physical distancing and mask use in response to the outbreak, whereas most measured patterns of social contacts remained stable during the course of the panel study. These findings will help better project, and respond to, future waves of the pandemic in Malawi and similar settings.

External jugular vein pierced by supraclavicular branches in a neonatal cadaver: a case report.

Anatomical variations in the venous structure and drainage patterns in the neck are not uncommon. However, this is the first known report on the external jugular vein being pierced by supraclavicular branches. In the lateral cervical region of a neonatal cadaver, the supraclavicular branches penetrated the external jugular vein superior to the clavicle, resulting in a circular venous channel formed around the nerve trunk. Variations such as these are important to note in order to minimize possible intra-operative complications sustained during surgical interventions such as venous catherization or nerve grafts.

The position of the common facial vein in neonates: An alternate route for central venous catheter placement.

INTRODUCTION: We determine the location of the common facial vein (CFV) in a sample of neonates and assess the safety of this vein as an alternative access route for a central venous catheter (CVC). MATERIALS AND METHODS: We dissected both the left and right sides of the neck region in 24 neonatal, formalin-fixed cadavers, exposing the underlying soft tissues and neurovascular structures. We identified the CFV, which we then pinned together with the internal jugular vein, cervical branch of facial nerve, marginal mandibular branch of the facial nerve, the cricoid cartilage, brachiocephalic vein, and the mastoid and sternal attachments of the sternocleidomastoid muscle. We measured the CFV and the related pinned structures. RESULTS: In neonates, the CFV intersected the anterior border of sternocleidomastoid on average 19.53 mm (left) and 21.73 mm (right) from its sternal attachment. CONCLUSION: We found the CFV inferior to the upper one third and just superior to half of the length of the sternocleidomastoid muscle, indicating a possible "safe-zone" where a skin incision could be made over the anteromedial border of sternocleidomastoid. The CFV is easily identified from surrounding landmarks. It could be used as a safe, alternative route for inserting a CVC if its average length (8.72 mm) and diameter (1.50 mm) are taken into account.