Rare case of combined vascular malformation of the face: a successful surgical management.

Combined vascular malformation affecting the facial region is an extremely rare clinical entity that is debilitating both functionally and emotionally. Treatment warrants a multidisciplinary approach with the aim of removing the vascular anomalies and ameliorating any functional facial disfigurement. Here, we present a case of a 40-year-old female with combined vascular malformation of the face who was treated successfully with surgical intervention accompanying significant resolution of facial disfigurement.

INNOVATIONS IN ARTIFICIAL ORGANS AND TISSUE ENGINEERING: FROM 3D PRINTING TO STEM CELL THERAPY.

"Every year, many individuals with tissue or organ problems require urgent care due to medical emergencies, burns, congenital anomalies, and other causes". Regenerative medicine was created because there aren't enough donors, issues with graft rejection, and insufficient organs or tissues for patients to replace, repair, and regenerate. However, significant tissue defects are difficult to fill with injections alone, making stem cell therapy a crucial component of the area of regenerative medicine. To achieve the intended outcome, the researchers combine stem cells with three-dimensional (3D) printed organs tissue engineering scaffolding. These scaffolds can resemble bone, cartilage, or "extracellular matrix (ECM)" in that they provide structural support and promote adhesion, proliferation, and differentiation, finally resulting in the production of functional tissues or organs. In this study on stem cell regenerative medicine, the therapeutic focused mostly on scaffolding for 3D printed organ tissue engineering. The following applications are demonstrated and compared using various 3D printing processes and starting materials. Then, we go over the benefits of 3D printing over conventional methods, touch on certain issues and restrictions, and make some assumptions about potential applications in the future.

Immunogenicity and safety of Mebella™ vaccine developed by Human Biologicals Institute in a Phase II/III, randomized, multicentric, non-inferiority study.

BACKGROUND: The goal of 'Measles and Rubella Strategic Framework 2021-2030' is to make "A world free from measles and rubella". To be a part of this journey, Human Biologicals Institute has developed Mebella™ vaccine, which is a lyophilized Measles and Rubella (Live) vaccine. A randomized, single blind, comparative, multicenter Phase II/III trial was conducted to compare the immunogenicity and safety of Mebella™ vaccine with MR-VAC® vaccine in healthy subjects. METHODS: A total of 888 subjects were enrolled in four age groups (222 subjects in each group) of 18 years to 49 years; 2 years to below 18 years; 12 months to below 24 months; and 9 months to below 12 months of age. The subjects were randomized in 2:1 ratio to receive single dose of either Mebella™ vaccine of Human Biologicals Institute or MR-VAC® vaccine. Immunogenicity was assessed at 42 days after the vaccination and was compared between the vaccine arms in each group. Safety was also assessed and compared between the vaccine arms during the study period. RESULTS: A total of 875 subjects completed the study out of 888 enrolled subjects. The seroprotection rates, seroconversion rates, and geometric mean titres for both Measles and Rubella components of Mebella™ vaccine were found to be comparable and non-inferior to the MR-VAC® vaccine after 42 days of vaccination. Injection site pain was the most common local adverse event reported whereas fever was the only systemic adverse event reported in both the vaccine arms. No serious adverse event was reported. CONCLUSION: It was concluded from the study results that the test vaccine, Mebella™, was immunogenic and well tolerated and was non-inferior to the comparator vaccine, MR-VAC®, when administered to healthy subjects of 9 months to 49 years of age. Clinical Trial Registry of India Identifier: CTRI/2020/07/026930.

Evaluation of cold atmospheric plasma for the decontamination of flexible endoscopes.

BACKGROUND: Despite adherence to standard protocols, residues including live micro-organisms may remain on the various surfaces of reprocessed flexible endoscopes. Prions are infectious proteins that are notoriously difficult to eliminate. AIM: To test the potential of cold atmospheric plasma (CAP) for the decontamination of various surfaces of flexible endoscopes, measuring total proteins and prion residual infectivity as indicators of efficacy. METHODS: New PTFE endoscope channels and metal test surfaces spiked with test soil or prion-infected tissues were treated using different CAP-generating prototypes. Surfaces were examined for the presence of residues using very sensitive fluorescence epimicroscopy. Prion residual infectivity was determined using the wire implant animal model and a more sensitive cell infectivity assay. FINDINGS: A CAP jet applied perpendicularly at close range on flat test surfaces removed soil within 3 min, but left microscopic residues and failed to eliminate prion infectivity according to the wire implant animal assay. The longitudinal gas flow from CAP prototypes developed for the treatment of long channels led to the displacement and sedimentation of residual soil towards the distal end, when applied alone. Observations of the plasma inside glass tubes showed temporal and spatial heterogeneity within a limited range. After the standard enzymatic manual pre-wash, 'CAP-activated' gas effluents prevented prion transmission from treated endoscope channels according to the prion infectivity cell assay. CONCLUSION: CAP shows promising results as a final step for decontamination of surgical surfaces. Optimizing CAP delivery could further enhance CAP efficacy, offering a safe, chemical-free alternative for the reprocessing of all luminal flexible endoscope surfaces.

Surgical outcomes of T4b oral cancers: assessment of prognostic factors and a need to re-evaluate the current staging system.

T4b oral cancer is a broad umbrella term for all advanced oral cancers, the prognosis of which varies drastically for disease of the same stage, according to the extent of the masticator space involvement. This was a retrospective observational study including all consecutive T4b oral squamous cell carcinoma patients treated surgically between January 2015 and January 2016 and followed up until January 2020. The disease was classified as upper disease or lower disease based on the anatomical location in relation to an imaginary plane passing through the base of the retromolar trigone. The prime objective was to evaluate overall survival and prognostic factors affecting overall survival. The projected 5-year overall and disease-free survival rates were 40.7% and 35.6%, respectively. The assessment of prognostic factors revealed that lower disease (lower anatomical subsites), bone invasion, and lymph nodal spread significantly affected survival. Patients with disease in an upper anatomical location without bone and nodal involvement can achieve fairly good survival (projected 5-year overall survival of 64.2%) when compared to the other subsets of patients. We propose a re-evaluation of the current staging system based on the prognostic features, so that all patients are not considered under a single stage, since their survival differs significantly.

Long-Term Exposure to AIR Pollution and COVID-19 Mortality and Morbidity in DENmark: Who Is Most Susceptible? (AIRCODEN).

INTRODUCTION: Early ecological studies have suggested a link between air pollution and Coronavirus Diseases 2019 (COVID-19); however, the evidence from individual-level prospective cohort studies is still sparse. Here, we have examined, in a general population, whether long-term exposure to air pollution is associated with the risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and developing severe COVID-19, resulting in hospitalization or death and who is most susceptible. We also examined whether long-term exposure to air pollution is associated with hospitalization or death due to COVID-19 in those who have tested positive for SARS-CoV-2. METHODS: We included all Danish residents 30 years or older who resided in Denmark on March 1, 2020. and followed them in the National COVID-19 Surveillance System until first positive test (incidence), COVID-19 hospitalization, or death until April 26, 2021. We estimated mean levels of nitrogen dioxide (NO2), particulate matter with an aerodynamic diameter <2.5 µm (PM2.5), black carbon (BC), and ozone (O3) at cohort participants' residence in 2019 by the Danish Eulerian Hemispheric Model/Urban Background Model. We used Cox proportional hazard models to estimate the associations of air pollutants with COVID-19 incidence, hospitalization, and mortality adjusting for age, sex, and socioeconomic status (SES) at the individual and area levels. We examined effect modification by age, sex, SES (education, income, wealth, employment), and comorbidities with cardiovascular disease, respiratory disease, acute lower respiratory infections, diabetes, lung cancer, and dementia. We used logistic regression to examine association of air pollutants with COVID-19-related hospitalization or death among SARS-CoV-2 positive patients, adjusting for age, sex, individual- and area-level SES. RESULTS: Of 3,721,810 people, 138,742 were infected, 11,270 hospitalized, and 2,557 died from COVID-19 during 14 months of follow-up. We detected strong positive associations with COVID-19 incidence, with hazard ratio (HR) and 95% confidence interval (CI) of 1.10 (CI: 1.05-1.14) per 0.5-µg/m3 increase in PM2.5 and 1.18 (CI: 1.14-1.23) per 3.6-µg/m3 increase in NO2. For COVID-19 hospitalizations and for COVID-19 deaths, corresponding HRs and 95% CIs were 1.09 (CI: 1.01-1.17) and 1.19 (CI: 1.12-1.27), respectively for PM2.5, and 1.23 (CI: 1.04-1.44) and 1.18 (CI: 1.03-1.34), respectively for NO2. We also found strong positive and statistically significant associations with BC and negative associations with O3. Associations were strongest in those aged 65 years old or older, participants with the lowest SES, and patients with chronic cardiovascular, respiratory, metabolic, lung cancer, and neurodegenerative disease. Among 138,742 individuals who have tested positive for SARS-Cov-2, we detected positive association with COVID-19 hospitalizations (N = 11,270) with odds ratio and 95% CI of 1.04 (CI: 1.01- 1.08) per 0.5-µg/m3 increase in PM2.5 and 1.06 (CI: 1.01-1.12) per 3.6-µg/m3 increase in NO2, but no association with PM with an aerodynamic diameter <10 µm (PM10), BC, or O3, and no association between any of the pollutants and COVID-19 mortality (N = 2,557). CONCLUSIONS: This large nationwide study provides strong new evidence in support of association between long-term exposure to air pollution and COVID-19.

A rare case of persistent lateral marginal vein of Servelle in Klippel Trenaunay Syndrome: A successful surgical management.

INTRODUCTION AND IMPORTANCE: Klippel-Trenaunay Syndrome (KTS) is a rare congenital vascular disorder characterized by capillary malformation, varicosities, and tissue overgrowth. It usually affects the unilateral lower extremities manifesting commonly as pain, localized rise of temperature, and venous tortuosity. However, in severe cases, ulceration, cellulitis, and chronic lymphatic malformation may be present. Management is mostly supportive and involves the use of compression stockings. CASE PRESENTATION: Here, we report a case of KTS with a persistent lateral marginal vein of Servelle managed with radiofrequency ablation along with sclerotherapy of selected perforators. On a two-year follow-up, the symptoms had resolved and Doppler ultrasonography revealed resolution of the defective vein along with the absence of incompetent perforators. CLINICAL DISCUSSION: In cases with venous malformation with the persistence of embryonic avalvular venous structures, like the lateral marginal vein of Servelle, surgical intervention is warranted especially at a younger age to reduce the risk of future thromboembolic events and recurrence. CONCLUSION: Varicosities of the lateral marginal vein of Servelle can be managed successfully by radiofrequency ablation and adjunct sclerotherapy in selected cases.

MUC1 and Polarity Markers INADL and SCRIB Identify Salivary Ductal Cells.

Current treatments for xerostomia/dry mouth are palliative and largely ineffective. A permanent clinical resolution is being developed to correct hyposalivation using implanted hydrogel-encapsulated salivary human stem/progenitor cells (hS/PCs) to restore functional salivary components and increase salivary flow. Pluripotent epithelial cell populations derived from hS/PCs, representing a basal stem cell population in tissue, can differentiate along either secretory acinar or fluid-transporting ductal lineages. To develop tissue-engineered salivary gland replacement tissues, it is critical to reliably identify cells in tissue and as they enter these alternative lineages. The secreted protein α-amylase, the transcription factor MIST1, and aquaporin-5 are typical markers for acinar cells, and K19 is the classical ductal marker in salivary tissue. We found that early ductal progenitors derived from hS/PCs do not express K19, and thus earlier markers were needed to distinguish these cells from acinar progenitors. Salivary ductal cells express distinct polarity complex proteins that we hypothesized could serve as lineage biomarkers to distinguish ductal cells from acinar cells in differentiating hS/PC populations. Based on our studies of primary salivary tissue, both parotid and submandibular glands, and differentiating hS/PCs, we conclude that the apical marker MUC1 along with the polarity markers INADL/PATJ and SCRIB reliably can identify ductal cells in salivary glands and in ductal progenitor populations of hS/PCs being used for salivary tissue engineering. Other markers of epithelial maturation, including E-cadherin, ZO-1, and partition complex component PAR3, are present in both ductal and acinar cells, where they can serve as general markers of differentiation but not lineage markers.

Stage specific comparative transcriptomic analysis to reveal gene networks regulating iron and zinc content in pearl millet [Pennisetum glaucum (L.) R. Br.].

Pearl millet is an important staple food crop of poor people and excels all other cereals due to its unique features of resilience to adverse climatic conditions. It is rich in micronutrients like iron and zinc and amenable for focused breeding for these micronutrients along with high yield. Hence, this is a key to alleviate malnutrition and ensure nutritional security. This study was conducted to identify and validate candidate genes governing grain iron and zinc content enabling the desired modifications in the genotypes. Transcriptome sequencing using ION S5 Next Generation Sequencer generated 43.5 million sequence reads resulting in 83,721 transcripts with N50 of 597 bp and 84.35% of transcripts matched with the pearl millet genome assembly. The genotypes having high iron and zinc showed differential gene expression during different stages. Of which, 155 were up-regulated and 251 were down-regulated while during flowering stage and milking stage 349 and 378 transcripts were differentially expressed, respectively. Gene annotation and GO term showed the presence of transcripts involved in metabolic activities associated with uptake and transport of iron and zinc. Information generated will help in gaining insights into iron and zinc metabolism and develop genotypes with high yield, grain iron and zinc content.

Nitrobenzene Induced Methemoglobinemia with Paroxysmal Atrial Fibrillation Treated with Single Volume Exchange Transfusions.

Methemoglobinemia is a potentially fatal condition if left untreated. Conventional treatment of nitrobenzene induced methemoglobinemia dictates the use of methylene blue, which is the antidote of choice. However, its availability in our setting is limited only to the laboratory use. We present a case of a 21-year-old female with intentional ingestion of nitrobenzene. Clinical history and supportive investigations revealed methemoglobinemia and it was successfully managed with single volume exchange transfusions in absence of specific antidote. While exchange transfusions are indicated for severe cases, it may be useful as an alternative treatment in acute life-threatening conditions where methylene blue is not available.

Rickettsial Infection amongst Febrile Illness Patient in a Tertiary Care Hospital: A Retrospective Cross-sectional Study.

Background Rickettsial infection is an emerging neglected tropical disease in the Southeast Asia. In past few years Nepal is also reporting escalating prevalence of rickettsia. The under evaluation is resulting it as undiagnosed or are simply labeled as pyrexia of unknown origin. Objective To find out the prevalence of rickettsia in a hospital setting, assess the sociodemographic and other relevant clinical features of the rickettsia patients. Method This is a hospital based retrospective cross-sectional study from October 2020 to October 2021. This study reviewed the medical records of the department. Result The study included 105 eligible patients and the prevalence rate was 4.38 per 100 patients. The mean age of the participants was 42 years, and the mean hospital stay was 3 (SD ±2.06) days. More than 55% of the participants had fever for less than or equal to 5 days and 9% had Eschar present. Vomiting, headache, and myalgia were the most common symptoms and hypertension, and diabetes were the common comorbidities. Pneumonia and the acute kidney injury were the two complications of the patients as stated in the study. The severity of the thrombocytopenia deducted from admission time to discharge, and the case fatality was 4%. Conclusion The future studies shall consider on collaborative clinical and entomological research. This would help in better understanding of the etiology of supposedly unknown febrile illness and the under-investigated field of emerging rickettsia in Nepal.

A proposed "Radiological Evaluation Score for Bone Tumors" (REST): An objective system for assessment of a radiograph in patients with suspected bone tumor.

BACKGROUND: Although radiographs have been widely used in the evaluation of patients with suspected bone tumors, the lack of an objective radiological assessment method leads to a challenge in reaching correct diagnosis. The study aimed to propose a Radiological Evaluation Score for Bone Tumors (REST) which includes eight radiological factors [characteristics, content, cortical breach, distinctiveness, distribution, periosteal reaction, fracture, and soft tissue swelling] to form a single score along with its validation by multidisciplinary observers. METHODS: We reviewed the radiographs of 100 patients with a primary bone tumor which were selected at random from the database between January 2017 and January 2019 of a tertiary cancer center. Four reviewers (two orthopedic oncologists and two surgical oncologists) independently assessed the radiographs, based on the reporting system of REST. We constituted two groups according to the probable diagnosis of bone tumor (suspected benign tumor and suspected malignant tumor). RESULTS: The mean score in the suspected benign tumor group was 1.1 (range 0-3, 95% CI 0.8-1.3) and in malignant tumor group was 6.1 (range 2-8, 95% CI 5.8-6.4). A receiver operator characteristic (ROC) curve for REST was with a cutoff of 3.5, with the most diagnostic value area under curve (AUC) of 0.99. The sensitivity was 98% and specificity was 100% with a positive predictive value of 100% and a negative predictive value of 98%. The inter-observer correlation coefficient was 0.985 (p value < 0.05), and Fleiss kappa value for the prediction of the benign or malignant lesion was 0.97 (p value < 0.05). The characteristics and content of tumor, cortical erosion, distinctiveness, distribution, periosteal reaction, and soft tissue mass had a significant correlation with the aggressiveness of bone lesion p value < 0.05. CONCLUSIONS: The Radiological Evaluation Score for Bone Tumors (REST) is a structured reporting and objective method for the assessment of radiographs in patients with suspected bone tumors. This method is a reliable and helpful tool for clinicians in their outdoor patient department to differentiate a radiograph of a suspected benign tumor from a malignant bone tumor.

Salvage surgery for recurrent carcinoma of the oral cavity: assessment of prognostic factors.

Salvage surgery is the most acceptable therapeutic option for disease control of loco-regional recurrences in oral cancers. Prognostic factors need to be assessed to select patients for salvage surgery who would benefit the most. This was a single-centre retrospective observational study conducted between 2015 and 2018. A total of 168 patients with recurrent oral cavity carcinoma who underwent salvage surgery were included for analysis. The primary endpoints of the study were to evaluate overall survival (rOS) after salvage surgery and prognostic factors affecting survival. In this study, the median rOS was 18 months and the median disease-free survival (rDFS) was 14 months. Advanced stage (hazard ratio (HR) 2.387, 95% confidence interval (CI) 1.496-3.808; P = 0.001) and multimodality treatment (HR 1.642, 95% CI 1.139-2.367; P = 0.008) in the initial disease, as well as nodal spread (HR 3.794, 95% CI 1.580-9.111; P = 0.008) and perineural invasion (HR 2.167, 95% CI 1.358-3.455; P = 0.001) in the recurrent disease, were found to adversely affect survival after salvage surgery. With thorough assessment of the prognostic factors and appropriate patient selection, survival may be favourable after salvage surgery for recurrent oral cavity carcinoma.

Aerosols optical depth and Ångström exponent over different regions in Garhwal Himalaya, India.

Aerosol optical depth (AOD) and Ångström exponent (AE) are observed to be important parameters in understanding the status of ambient aerosol concentration over a particular location and depend not only upon the local but also on the large-scale dynamics of the atmosphere. The present article analyses the AOD and AE parameters retrieved with Moderate Resolution Imaging Spectrometer (MODIS) and Multi-angle Imaging Spectro-Radiometer (MISR) instruments onboard satellites, for the upper (Chamoli) and foothill (Dehradun) regions of Garhwal Himalaya in Uttarakhand, India, from 2006 to 2015. Aerosol properties are investigated at monthly, seasonal, and annual scales. The monthly mean values of MODIS-derived AOD and AE were observed to be 0.18 (± 0.14) and 1.05 (± 0.43) respectively over the Dehradun region. The seasonal maximums in AOD with MODIS and MISR were observed as 0.23 ± 0.06 and 0.29 ± 0.07 respectively in the pre-monsoon season, and the minimum values (0.099 ± 0.02) were observed in the post-monsoon season, over the Dehradun region. In contrast, in the Chamoli region, the maximum AOD (MODIS) was 0.21 ± 0.06 observed in the monsoon season and the minimum was 0.036 ± 0.007 in the post-monsoon season. Over a decade, the AE for Chamoli and Dehradun was found to vary from 0.07 to 0.17 and from 0.14 to 0.20 respectively. The median AE for Chamoli and Dehradun was found to be 1.49 and 1.47 respectively, marking the dominance of fine mode particles of anthropogenic origin. Observations show the presence of dust and polluted dust resulting from the long-range transport from the west. The comparison of AOD values from the two sensors shows a significant correlation (0.73) with slightly higher values from MISR over the year. The results obtained are important in understanding the climatic implications due to the atmospheric aerosols over the abovementioned Himalayan region of Uttarakhand, India.

Pregnancy outcomes following in vitro fertilization frozen embryo transfer (IVF-FET) with or without preimplantation genetic testing for aneuploidy (PGT-A) in women with recurrent pregnancy loss (RPL): a SART-CORS study.

STUDY QUESTION: Can preimplantation genetic testing for aneuploidy (PGT-A) improve the live birth rate in patients with recurrent pregnancy loss (RPL)? SUMMARY ANSWER: PGT-A use was associated with improved live birth rates in couples with recurrent pregnancy loss undergoing frozen embryo transfer (IVF-FET). WHAT IS KNOWN ALREADY: Euploid embryo transfer is thought to optimize outcomes in some couples with infertility. There is insufficient evidence, however, supporting this approach to management of recurrent pregnancy loss. STUDY DESIGN, SIZE, DURATION: This study included data collected by the Society of Assisted Reproductive Technologies Clinical Outcomes Reporting System (SART-CORS) for IVF-FET cycles between years 2010 through 2016. A total of 12 631 FET cycles in 10 060 couples were included in this analysis designed to assess the utility of PGT-A in couples with RPL undergoing FET, including 4287 cycles in couples with tubal disease who formed a control group. PARTICIPANTS/MATERIALS, SETTING, METHODS: The experimental group included couples with RPL (strictly defined as a history of 3 or more pregnancy losses) undergoing FET with or without PGT-A. The primary outcome was live birth rate. Secondary outcomes included rates of clinical pregnancy, spontaneous abortion, and biochemical pregnancy loss. Differences were analyzed using generalized estimating equations logistic regression models to account for multiple cycles per patient. Covariates included in the model were age, gravidity, geographic region, race/ethnicity, smoking history, and indication for assisted reproductive technologies. Analyses were stratified for age groups as defined by SART: <35 years, 35-37 years, 38-40 years, 41-42 years, and >42 years. MAIN RESULTS AND THE ROLE OF CHANCE: In women with a diagnosis of RPL, the adjusted odds ratio (OR) comparing IVF-FET with PGT-A versus without PGT-A for live birth outcome was 1.31 (95% CI: 1.12, 1.52) for age <35 years, 1.45 (95% CI: 1.21, 1.75) for ages 35-37 years, 1.89 (95% CI: 1.56, 2.29) for ages 38-40, 2.62 (95% CI: 1.94-3.53) for ages 41-42, and 3.80 (95% CI: 2.52, 5.72) for ages >42 years. For clinical pregnancy, the OR was 1.26 (95% CI: 1.08, 1.48) for age <35 years, 1.37 (95% CI: 1.14, 1.64) for ages 35-37 years, 1.68 (95% CI: 1.40, 2.03) for ages 38-40 years, 2.19 (95% CI: 1.65, 2.90) for ages 41-42, and 2.31 (95% CI: 1.60, 3.32) for ages >42 years. Finally, for spontaneous abortion, the OR was 0.95 (95% CI: 0.74, 1.21) for age <35 years, 0.85 (95% CI: 0.65, 1.11) for ages 35-37 years, 0.81 (95% CI: 0.60, 1.08) for ages 38-40, 0.86 (95% CI: 0.58, 1.27) for ages 41-42, and 0.58 (95% CI: 0.32, 1.07) for ages >42 years. LIMITATIONS, REASONS FOR CAUTION: The retrospective collection of data including only women with recurrent pregnancy loss undergoing FET presents a limitation of this study, and results may not be generalizable to all couples with recurrent pregnancy loss. Also, data regarding evaluation and treatment for RPL for the included women is unavailable. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest study to date assessing the utility of PGT-A in women with RPL. PGT-A was associated with improvement in live birth and clinical pregnancy in women with RPL, with the largest difference noted in the group of women with age greater than 42 years. Couples with RPL warrant counseling on all management options to reduce subsequent miscarriage, which may include IVF with PGT-A for euploid embryo selection. STUDY FUNDING/COMPETING INTEREST(S): There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

A proposed ''A to Z RAM (Radiograph Assessment Method)'' for triage of patients with a suspected bone tumour.

INTRODUCTION: We propose a ''A to Z RAM (Radiograph Assessment Method)'' for evaluation of Radiograph of patients with a suspected bone tumour. METHODS: In the current study, ten radiological features with letters 'A, B, C, D, E, F and Z' were used and which included the age of the patient, involved part of the bone, characteristics, content, distinctiveness, the exterior of the bone, fracture, and zone of transition. Four independent observers (orthopaedic oncologists and surgical oncologists) evaluated a set of 30 radiographs of bone tumour selected at random from our hospital database based on A to Z RAM. We classified the lesions into two groups according to the traffic signal system; Green (suspected benign lesion) and Red (suspected malignant lesion). RESULTS: There were 18 (60%) benign bone lesions and 12 (40%) malignant lesions in the current study. 91.6% of malignant tumours and 88.8% of the benign tumours were identified correctly by the four observers. The inter-observer variability with Fleiss kappa was 0.884 (95% CI 0.7-1.03 p-value < 0.05), suggestive of agreement not by chance. These radiographs were again reassessed by the four observers after 3 months. The interobserver variability by Fleiss kappa was 1.0 (95% CI 0.8-1.1) suggesting complete agreement amongst the observers. Both orthopaedic oncologists had intra-observer kappa as 1.0 each and both surgical oncologists had 0.795 and 0.930 respectively. CONCLUSION: The proposed A to Z RAM is an easy to use and reproducible method for reviewing radiographs in the out-patient department along with clinical findings for better management of patients with suspected bone lesions. The A to Z RAM can be a medical triage tool and subdivide bone lesions into two subgroups i.e. suspected benign lesion with a suggestion of further investigations with MRI and biopsy and suspected malignant lesion with a suggestion of MRI or early referral to a tertiary cancer center with expertise in orthopaedic oncology. IMPLICATIONS FOR PRACTICE: The A to Z RAM (Radiologic Assessment Method) is a reproducible method for reviewing radiographs in the out-patient department and can be an aid for better management of patients. A to Z RAM is useful as a medical triage system, subdividing patients according to the probable diagnosis into a suspected benign lesion and suspected malignant lesion.

Med23 Regulates Sox9 Expression during Craniofacial Development.

The etiology and pathogenesis of craniofacial birth defects are multifactorial and include both genetic and environmental factors. Despite the identification of numerous genes associated with congenital craniofacial anomalies, our understanding of their etiology remains incomplete, and many affected individuals have an unknown genetic diagnosis. Here, we show that conditional loss of a Mediator complex subunit protein, Med23 in mouse neural crest cells (Med23fx/fx;Wnt1-Cre), results in micrognathia, glossoptosis, and cleft palate, mimicking the phenotype of Pierre Robin sequence. Sox9 messenger RNA and protein levels are both upregulated in neural crest cell-derived mesenchyme surrounding Meckel's cartilage and in the palatal shelves in Med23fx/fx;Wnt1-Cre mutant embryos compared to controls. Consistent with these observations, we demonstrate that Med23 binds to the promoter region of Sox9 and represses Sox9 expression in vitro. Interestingly, Sox9 binding to ß-catenin is enhanced in Med23fx/fx;Wnt1-Cre mutant embryos, which, together with downregulation of Col2a1 and Wnt signaling target genes, results in decreased proliferation and altered jaw skeletal differentiation and cleft palate. Altogether, our data support a cell-autonomous requirement for Med23 in neural crest cells, potentially linking the global transcription machinery through Med23 to the etiology and pathogenesis of craniofacial anomalies such as micrognathia and cleft palate.

Global maps of travel time to healthcare facilities.

Access to healthcare is a requirement for human well-being that is constrained, in part, by the allocation of healthcare resources relative to the geographically dispersed human population1-3. Quantifying access to care globally is challenging due to the absence of a comprehensive database of healthcare facilities. We harness major data collection efforts underway by OpenStreetMap, Google Maps and academic researchers to compile the most complete collection of facility locations to date. Leveraging the geographically variable strengths of our facility datasets, we use an established methodology4 to characterize travel time to healthcare facilities in unprecedented detail. We produce maps of travel time with and without access to motorized transport, thus characterizing travel time to healthcare for populations distributed across the wealth spectrum. We find that just 8.9% of the global population (646 million people) cannot reach healthcare within one hour if they have access to motorized transport, and that 43.3% (3.16 billion people) cannot reach a healthcare facility by foot within one hour. Our maps highlight an additional vulnerability faced by poorer individuals in remote areas and can help to estimate whether individuals will seek healthcare when it is needed, as well as providing an evidence base for efficiently distributing limited healthcare and transportation resources to underserved populations both now and in the future.