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Diabetic foot ulcers (DFUs) pose a significant clinical challenge, characterized by impaired wound healing, chronic inflammation, and increased risk of infection. Neutrophils, as critical components of the innate immune response, play a pivotal role in the initial stages of wound healing, particularly during the inflammatory phase. This review explores the intricate relationship between neutrophil migration, inflammation, and the pathogenesis of DFU and drugs that can impact neutrophil production and migration. Neutrophils contribute to infection control through phagocytosis and release pro-inflammatory cytokines and reactive oxygen species, which, when dysregulated, can impede the wound healing process. Furthermore, the chronic hyperglycemic state characteristic of diabetes mellitus has been implicated in impairing neutrophil functions, including chemotaxis and oxidative burst. This compromised neutrophil response prolongs the inflammatory phase and disrupts the delicate balance required for efficient wound healing. Neutrophil extracellular traps (NETs), a unique form of neutrophil defence, have also been implicated in DFU pathogenesis, potentially exacerbating inflammation and tissue damage. Understanding the intricate interplay between neutrophil migration, dysregulated inflammatory responses, and hyperglycemia-driven impairments is essential for developing targeted therapeutic strategies for DFUs. This review sheds light on the critical role of neutrophils in DFU pathogenesis, and innovative and advanced treatment strategies for DFU, highlighting the potential for novel interventions to restore the balance between pro-inflammatory and wound healing processes, ultimately improving clinical outcomes for individuals with DFU., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Wound healing is a complex biological process crucial for tissue repair, wherein keratinocytes play a pivotal role in initiating, sustaining and completing the cascade. Various local and systemic factors, such as lifestyle, age metabolic disorders and vascular insufficiency, can influence this process, and in the context of diabetic wounds, disrupted biological mechanisms, including inflammation, tissue hypoxia, decrease in collagen production along with increased oxidative stress and keratinocyte dysfunction, contribute to delayed healing. During re-epithelialisation, keratinocytes undergo rapid multiplication and migration, forming a dense hyperproliferative epithelial layer that restores the epidermal barrier. Nuclear factor-erythroid 2-related factor (Nrf2), a vital transcription factor, emerges as a central regulator in managing antioxidant proteins and detoxifying enzymes, serving as a guardian against elevated reactive oxygen species (ROS) levels during stress. Nrf2 also orchestrates angiogenesis and anti-inflammatory responses crucial for wound repair. Studies demonstrate that under high-glucose conditions, Nrf2 activation promotes wound healing by enhancing cell proliferation and migration while reducing apoptosis. Nrf2 activators stimulate endogenous antioxidant production, thereby mitigating oxidative stress. Furthermore, Nrf2 upregulation is associated with decreased expression of cytokines such as TNF-α and IL- 6. Recent research underscores the potential of bioactive molecules, including dietary polyphenols, traditional medicinal compounds and pharmacological agents, in activating Nrf2 and preventing diseases such as diabetes due to their robust antioxidative properties. This review aims to investigate the activation of Nrf2 by these bioactive molecules in cultured keratinocytes and animal models, elucidating the key molecular regulatory mechanisms involved in alleviating oxidative stress and facilitating the diabetic wound healing process. Understanding these complex pathways may offer insights into novel therapeutic strategies for enhanced wound healing in diabetes-associated complications., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Diabetic nephropathy (DN), a severe complication of type 2 diabetes mellitus (T2DM), is marked by heightened endoplasmic reticulum stress (ERS) and oxidative stress (OS) due to protein misfolding and free radical generation. We investigated the sodium-glucose co-transporter-2 inhibitor (SGLT2i), canagliflozin (Cana), in alleviating ERS and OS in DN patients and THP-1 cells under hyperglycemic condition. A total of 120 subjects were divided into four groups, with 30 subjects in each group: healthy controls, T2DM individuals, DN patients receiving standard treatment, and those treated with Cana. The control group had no history of diabetes, cardiovascular or renal diseases, or other comorbidities. Cana was administered at doses of either 100 or 300 mg per day based on the estimated glomerular filtration rate (eGFR) value of DN individuals, with a mean follow-up of 6 months. Additionally, THP-1 monocytes were exposed to HGM (33.3 mM glucose with a cytokine cocktail of TNF-α and IFN-γ at 50 ng/mL each) to evaluate the relative levels of ERS, OS markers, and nuclear factor erythroid 2-related factor 2 (Nrf2), the transcription factor regulating cellular redox, which is downregulated in diabetes. Our results revealed that ERS markers GRP78 and PERK, as well as OS markers TXNIP and p22phox, were elevated in both DN patients and HGM-treated THP-1 monocytes and were reduced by Cana intervention. Furthermore, Cana regulated the phosphorylation of Nrf2, Akt, and EIF2α in HGM-treated monocytes. In conclusion, our findings highlight the role of Cana in activating Nrf2, thereby attenuating ERS and OS to mitigate DN progression., (© 2024, The American College of Clinical Pharmacology.)

Peripheral nerve blocks provide a safe and reliable alternative in the anesthetic management of femur fractures in elderly subpopulations associated with significant comorbidities. Single-Insertion Multiple Nerve Block Anesthesia (SIMBA) is a technique where a single needle insertion is used to block all four nerves that supply the femur shaft: the femoral nerve, obturator nerve, lateral femoral cutaneous nerve, and sciatic nerve. The authors performed this technique in 11 cardiac compromised geriatric patients with midshaft/distal femur fractures, and the surgery was conducted successfully without any significant hemodynamic change and good postoperative analgesia., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

Background: Hepatic encephalopathy (HE) severe complication of liver cirrhosis with high mortality. Few studies have found zinc deficiency in liver cirrhosis and HE patients and found it as a precipitating factor for the development of HE. This study was done to measure the serum zinc level in patients with liver cirrhosis with HE and a correlation was obtained between serum zinc level with grades of HE., Material and Methods: A cross-sectional observational study was done on 150 patients with liver cirrhosis with HE at a tertiary care center in Jharkhand. All cases were evaluated by history taking, clinical examination, and a questionnaire and classified into different WHC grades of HE and CPC classes of cirrhosis. Routine blood investigations, imaging studies, and morning serum zinc levels were done for all patients., Results: Majority of patients with liver cirrhosis with HE had zinc deficiency. There was a statistically highly significant ( P < .00001) association between low serum zinc levels and WHC grades of HE. The serum zinc levels in different classes of cirrhosis showed highly significant differences ( P < .00001). The mean serum zinc level was significantly low in patients who died (35.56 ± 11.65 vs 48.36 ± 10.91, P < .0001). The study revealed a strong positive correlation (r = .88, P = .048) between serum zinc and serum albumin levels., Conclusion: Serum zinc is deficient in patients with liver cirrhosis and HE. Zinc deficiency is significantly associated with higher severity of cirrhosis and higher grades of HE. All patients with liver cirrhosis with HE and hypoalbuminemia should be evaluated for zinc deficiency., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family Medicine and Primary Care.)

Hexagonal boron nitride is rapidly gaining interest as a platform for photonic quantum technologies, due to its two-dimensional nature and its ability to host defects deep within its large band gap that may act as room-temperature single-photon emitters. In this review paper we provide an overview of (1) the structure, properties, growth and transfer of hexagonal boron nitride; (2) the creationof colour centres in hexagonal boron nitride and assignment of defects by comparison with ab initio calculations for applications in photonic quantum technologies; and (3) heterostructure devices for the electrical tuning and charge control of colour centres that form the basis for photonic quantum technology devices. The aim of this review is to provide readers a summary of progress in both defect engineering and device fabrication in hexagonal boron nitride based photonic quantum technologies.

Over the last decade, CRISPR has revolutionized drug development due to its potential to cure genetic diseases that currently do not have any treatment. CRISPR was adapted from bacteria for gene editing in human cells in 2012 and, remarkably, only 11 years later has seen it's very first approval as a medicine for the treatment of sickle cell disease and transfusion-dependent beta-thalassemia. However, the application of CRISPR systems is associated with unintended off-target and on-target alterations (including small indels, and structural variations such as translocations, inversions and large deletions), which are a source of risk for patients and a vital concern for the development of safe therapies. In recent years, a wide range of methods has been developed to detect unwanted effects of CRISPR-Cas nuclease activity. In this review, we summarize the different methods for off-target assessment, discuss their strengths and limitations, and highlight strategies to improve the safety of CRISPR systems. Finally, we discuss their relevance and application for the pre-clinical risk assessment of CRISPR therapeutics within the current regulatory context., Competing Interests: Authors RL and MKP are employed by F Hoffmann-La Roche Ltd., (Copyright © 2024 Lopes and Prasad.)

Background: Worldwide stroke is the second major cause of mortality and the fourth prominent cause of disease load after coronary heart disease and all types of malignancy. Greater than 3/4 th of these cases are in low-priced and middle-priced nations. Several epidemiological studies have shown that alcohol consumption is a risk factor for stroke. The correlation between alcohol consumption and stroke involves various processes. For excessive alcohol consumption, GGT (gamma glutamyl transferase) is used as a marker. The study aims to see whether serum GGT level is an independent risk factor for stroke in young and elderly patients who do not have a history of alcohol intake., Material and Method: The study is an analytical cross-sectional comparative hospital-based study done in the Department of Medicine, RIMS, Ranchi from November 2019 to April 2021. A total number of 100 cases including both sexes who presented with the first episode of stroke have been compared with 100 age-sex-matched healthy control subjects without any cerebrovascular or cardiovascular disease meeting inclusion and exclusion criteria. Analysis of data is done by SPSS software and R studio software., Result: Serum GGT is lower in the age group of 40-60 years (24-hour GGT mean 50.70 U/L+SD 16.86) than the age group of 60-80 years (24-hour GGT 65.89 U/L+SD59.04) with a P value of 0.005. This is also true in 48-hour GGT (48.02 U/L+SD16.02) in 40-60 years compared to 57.94 U/L+SD42.81 in 60-80 years with a P value of 0.001 and 72-hour GGT (44.80 U/L+SD16.98) in 40-60 years compared to the mean (56.16 U/L+SD43.82) in 60-80 years with a P value of 0.001. This suggests that serum GGT level is significantly lower in the 40-60 years age group with a P value < 0.01. The serum GGT level in the case population is mean 58.30 (U/L) + SD43.87, and that in the control group is mean 17.48 (U/L) + SD4.32 with P value < 0.001. This implies an increased level of serum GGT level in stroke patients., Conclusion: Serum GGT level is independently correlated with stroke even in the presence of other risk factors for stroke such as diabetes mellitus, hypertension, and dyslipidemia. Serum GGT level is more in hypertensive, dyslipidemic, and ischemic stroke patients than in non-hypertensive, non-dyslipidemic, non-ischemic stroke patients, but serum GGT level cannot predict the outcome (survival or death) in stroke patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Family Medicine and Primary Care.)

Background High neutrophil-to-lymphocyte ratio (NLR) may be used as a reliable measure of vascular complications and an indicator of poor outcomes in cases of diabetes mellitus (DM). Methods A prospective analytical cross-sectional observational study was conducted at the Rajendra Institute of Medical Sciences (RIMS), Ranchi, Jharkhand, India. A total of 100 patients with DM who met the inclusion and exclusion criteria were included in the study. A pre-tested and semi-structured questionnaire was given to the patients. IBM SPSS software version 26 (IBM Corp., Armonk, NY, USA) and MedCalc trial version 20.114 (MedCalc Software Ltd., Ostend, Belgium) were used for data analysis. Logistic regression analysis was performed to determine the association of the NLR with microvascular complications. Results In our study, the male-to-female ratio was 1.78:1 (male: 64 (n)%, female: 36 (n)%). The mean age of our study population was 56.28 ± 13.24 years. Of 58 patients with microvascular complications, 34 had a high NLR, and 24 patients had a normal NLR. Of 42 patients without microvascular complications, only 14 had a high NLR, and the remaining 28 patients had a normal NLR (p = 0.012). Logistic regression was performed to analyze the association between the NLR and microvascular complications, which demonstrated a significant association (odds ratio (OR): 2.833, 95% confidence interval (CI): 1.238-6.481; p = 0.013). Conclusions Our study demonstrated the higher odds of having microvascular complications among diabetics with a high NLR compared with non-diabetics. Therefore, the NLR may be used as a measure of microvascular complications in the diabetic population., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Mahajan et al.)

Blood centers, which are arguably the backbone of every hospital, depend on blood donors for a constant and regular supply of blood. Like many other fields, the COVID-19 pandemic severely affected blood donations. In this article, we aim to systematically search the studies done on blood donation during the COVID-19 pandemic period, analyze the pandemic's effect on blood donation, and examine the methodology used to overcome the problem. We performed a systematic review and meta-analysis to investigate the effect of the COVID-19 pandemic on blood donation. Two independent reviewers searched different databases, such as PubMed, ProQuest, Scopus, and Google Scholar. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Joanna Briggs Institute critical appraisal checklist for overall study characteristics. We included a total of 15 studies. There was an overall decrease in blood donation of 25%, with some regions showing a decrease of as much as 71%. However, some regions were able to experience a 2-10% increase in blood donation after taking stringent and early measures to prevent such decreases. The COVID-19 pandemic and consequent lockdown greatly affected blood transfusion services, resulting in a progressive decline in blood donations that threatened the lives of many patients who were fully dependent on blood transfusion. However, by making appropriate and early decisions and taking action, policymakers and the rest of society can prevent such shortages, potentially saving millions of lives., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Kumar et al.)

Background and Aims: Laparoscopic cholecystectomy (LC) is a widely accepted surgical procedure associated with postoperative pain. This study was done to compare peripheral nerve stimulator (PNS)-guided serratus anterior plane block (SAP) and transversus abdominis plane (TAP) block for postoperative analgesia for patients undergoing LC., Methods: Following approval from the ethical committee, 70 patients for LC were randomly assigned to Group S: SAP block and Group T: TAP block. The blocks were performed under PNS guidance, and 20 ml of 0.375% ropivacaine was administered. The severity of pain was measured using a visual analogue scale (VAS). The study's primary objective was the evaluation of the postoperative VAS score. The time of the first dose of rescue analgesia and total tramadol consumption for 24 h postoperatively were secondary objectives. All the statistical calculation was done using statistical analyses for Social Sciences for Windows version 23.0 (IBM Corp, NY, USA)., Results: Lower VAS score was seen in patients of TAP block at rest as well as movement at 6 h ( P = 0.001), 12 h ( P = 0.001) and 18 h ( P = 0.001) postoperatively compared with SAP. The TAP group showed a significantly increased time of first rescue analgesic compared to the SAP group (7.97 ± 0.51 vs. 5.89 ± 1.45, P = 0.001). Tramadol usage was significantly higher in the SAP group than in the TAP group (128.9 ± 36.22 vs. 72.43 ± 44.80, P = 0.001)., Conclusion: TAP block guided by the PNS improves postoperative pain with less tramadol consumption and during the postoperative period without significant complications., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Anaesthesia.)

Pancreatic beta-cell death has been established as a critical mediator in the progression of type 1 and type 2 diabetes mellitus. Beta-cell death is associated with exacerbating hyperglycemia and insulin resistance and paves the way for the progression of DM and its complications. Apoptosis has been considered the primary mechanism of beta-cell death in diabetes. However, recent pieces of evidence have implicated the substantial involvement of several other novel modes of cell death, including autophagy, pyroptosis, necroptosis, and ferroptosis. These distinct mechanisms are characterized by their unique biochemical features and often precipitate damage through the induction of cellular stressors, including endoplasmic reticulum stress, oxidative stress, and inflammation. Experimental studies were identified from PubMed literature on different modes of beta cell death during the onset of diabetes mellitus. This review summarizes current knowledge on the crucial pathways implicated in pancreatic beta cell death. The article also focuses on applying natural compounds as potential treatment strategies in inhibiting these cell death pathways., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Single-cell and single-nucleus RNA sequencing have become common laboratory applications due to the wealth of transcriptomic information that they provide. Single nucleus RNA sequencing, particularly, is useful for investigating gene expression in difficult-to-dissociate tissues. Furthermore, this approach is also compatible with frozen (archival) material. Here, we describe a protocol to isolate high-quality single nuclei from frozen mammalian tissues for downstream single nucleus RNA sequencing in a partially-automated manner using commercially available instruments and reagents. Specifically, a robotic dissociator is used to automate and standardize tissue homogenization, followed by an optimized chemical gradient to filter the nuclei. Lastly, we accurately and automatically count the nuclei using an automated fluorescent cell counter. The performance of this protocol is demonstrated on mouse brain, rat kidney, and cynomolgus liver and spleen tissue. This protocol is straightforward, rapid, and readily adaptable to various mammalian tissues without requiring extensive optimization and provides good quality nuclei for downstream single nuclei RNA sequencing.

Tuberculous meningitis is the most serious complication of tuberculosis. Early diagnosis is crucial to start relevant treatment to prevent death and disability. Electronic databases PubMed, Google Scholar, and Cochrane Library were used to find relevant articles from January 1980 to June 2022. The random-effect model in terms of pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with 95% confidence interval was adopted to derive the diagnostic efficacy of cerebrospinal fluid (CSF) adenosine deaminase (ADA) for the diagnosis of tuberculous meningitis (TBM) in adult patients. A total of 22 studies (20 prospective and two retrospective data) have been included in this meta-analysis, having 1927 participants. We perceived acceptable pooled sensitivity, specificity, summary receiver operating characteristics (SROCs), and diagnostic odds ratio (DOR) of 0.85 (95% CI: 0.77-0.90), 0.90 (95% CI: 0.85-0.93), 0.94 (95% CI: 0.91-0.96) and 48 (95% CI: 26-86), respectively, for CSF-ADA for differentiating TBM from non-TBM in adult patients. To ascertain the certainty of evidence for CSF-ADA as a diagnostic marker for TBM, Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) analysis was used. CSF-ADA is an auspicious diagnostic test with a high degree of specificity and acceptable sensitivity for the diagnosis of tuberculous meningitis, however, with very low certainty of evidence., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Prasad et al.)

Background: Tuberculous peritonitis is difficult to diagnose due to its non-specific clinical manifestations and lack of proper diagnostic modalities. Current meta-analysis was performed to find the overall diagnostic accuracy of adenosine deaminase (ADA) in diagnosing tuberculous peritonitis., Materials and Methods: PubMed, Google Scholar, and Cochrane library were searched to retrieve the published studies which assessed the role of ascitic fluid ADA in diagnosing tuberculous peritonitis from Jan 1980 to June 2022. This meta-analysis included 20 studies and 2,291 participants after fulfilling the inclusion criteria., Results: The pooled sensitivity was 0.90 (95% confidence interval [CI]: 0.85 - 0.94) and pooled specificity was 0.94 (95% CI: 0.92 - 0.95). The positive likelihood ratio was 15.20 (95% CI: 11.70 - 19.80), negative likelihood ratio was 0.10 (95% CI: 0.07 - 0.16) and diagnostic odds ratio was 149 (95% CI: 86 - 255). The area under the summary receiver operating characteristic curve was 0.97. Cut- off value and sample size were found to be the sources of heterogeneity in the mete-regression analysis., Conclusion: Ascitic fluid ADA is a useful test for the diagnosis of tuberculous peritonitis with good sensitivity and specificity however, with very low certainty of evidence evaluated by Grading of Recommendations, Assessment, Development and Evaluation approach. Further well- designed studies are needed to validate the diagnostic accuracy of ascitic fluid ADA for tuberculous peritonitis., Competing Interests: No conflict of interest., (Copyright © 2023 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Validation of a risk factor in a multifactorial disease like ischemic stroke is necessary to practice precision medicine. Many risk factors have been attributed to causing ischemic stroke but contribute very little to it. There are many risk factors that need to be validated, and fibrinogen is one such risk factor. Using a meta-analysis technique, we investigated fibrinogen as a risk factor for ischemic stroke. We searched the computerized databases such as PubMed, Google Scholar, and Cochrane to explore articles on ischemic stroke. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random effects model. A total of 10 case-control studies with 6877 cases and 7219 controls were included in the study that match inclusion and exclusion criteria. The Asiatic population was portrayed in four studies, whereas the Caucasian population was portrayed in six studies. Under the recessive model, an elevated level of serum fibrinogen is linked to an increased risk of ischemic stroke as shown by pooled odds ratio (OR: 1.47, 95% CI: 1.19-1.76, I 2 = 78.3%, P = 0.000). Our meta-analysis concluded that a high level of fibrinogen is associated with an increased risk of ischemic stroke., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Prasad et al.)

Dengue fever, which is spread by Aedes mosquitoes, has claimed many lives in Kerala, with the Thiruvananthapuram district bearing the brunt of the toll. This study aims to demarcate the dengue risk zones in Thiruvananthapuram district using the analytical hierarchy process (AHP) and the fuzzy-AHP (F-AHP) methods. For the risk modelling, geo-environmental factors (normalized difference vegetation index, land surface temperature, topographic wetness index, land use/land cover types, elevation, normalized difference built-up index) and demographic factors (household density, population density) have been utilized. The ArcGIS 10.8 and ERDAS Imagine 8.4 software tools have been used to derive the risk zone maps. The area of the risk maps is classified into five zones. The dengue risk zone maps were validated using dengue case data collected from the Integrated Disease Surveillance Programme portal. From the receiver operating characteristic (ROC) curve analysis and the area under the ROC curve (AUC) values, it is proved that the F-AHP method (AUC value of 0.971) has comparatively more prediction capability than the AHP method (AUC value of 0.954) in demarcating the dengue risk zones. Also, based on the comparison of the risk zone map with actual case data, it was confirmed that around 82.87% of the dengue cases occurred in the very high and high-risk zones, thus proving the efficacy of the model. According to the dengue risk map prepared using the F-AHP model, 9.09% of the area of Thiruvananthapuram district is categorized as very high risk. The prepared dengue risk maps will be helpful for decision-makers, staff with the health, and disaster management departments in adopting effective measures to prevent the risks of dengue spread and thereby minimize loss of life., Competing Interests: Conflicts of interestDisclosure of potential conflicts of interest The authors have no conflicts of interest to declare., (© The Author(s), under exclusive licence to Springer Nature B.V. 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Transfusion of blood and blood products has many adverse effects and should be done only if patient benefits outweigh the associated risks. Current understanding of blood transfusion has improved dramatically, revolutionising the care of surgical, trauma, obstetric and critically ill patients. Most guidelines advise a restrictive approach for stable patients with non-haemorrhagic anaemia for red blood cell transfusion. The rationale for red blood cell transfusion has historically been to improve oxygen transport capacity and consumption-related parameters in anaemic patients. Current understanding casts serious doubts about the true potential of red blood cell transfusions to improve these factors. There may not be any benefit from blood transfusion beyond a haemoglobin threshold of 7 g/dL. In fact, liberal transfusion may be associated with higher complications. Guideline-based transfusion policy should be adopted for the administration of all blood products including fresh frozen plasma, platelet concentrates and cryoprecipitate etc. This should be integrated with clinical judgement., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Anaesthesia.)

Background Some literature has shown a high prevalence of pre-clinical diastolic dysfunction in subjects with type 2 diabetes mellitus. The current study was carried out to determine the association of glycosylated hemoglobin (HbA1c) levels with left ventricular diastolic dysfunction (LVDD) in patients with type 2 diabetes. Methods An observational cross-sectional study was conducted in a tertiary health care center in Jharkhand. A total of 100 subjects diagnosed with type 2 diabetes mellitus who gave informed consent and fulfilled the inclusion and exclusion criteria were studied in our center from April 2019 to September 2020. Logistic regression was carried out to determine the association of potential variables with outcomes. Multivariable logistic regression analysis was conducted to determine the independent effects of variables for LVDD prediction. Results The mean HbA1c of the population with LVDD was found to be higher (11.07 ± 3.66%) as compared to the population with normal LVDD (9.11 ± 2.95%), which was found statistically significant (probability value (P) =0.004). This signifies that a higher level of HbA1c in a patient with diabetes will have a higher incidence of LVDD. On applying multivariate analysis to determine the independent effect of variables for LVDD, HbA1C was found to be significant with an odds ratio (OR) of 1.26, 95% CI 1.08-1.48. The duration of diabetes was also found to be significant with OR 1.48 and CI 95 % (1.20-1.82) P <0.001. On plotting the receiver operating characteristic curve (ROC), the area under the ROC curve to predict the left ventricular function with the model was 0.8137. Conclusions Patients who have higher HbA1C are linked to a higher risk of left ventricular diastolic dysfunction in patients with type 2 diabetes. The combination of diabetes and left ventricular dysfunction can lead to increase morbidity and mortality in those patients in whom it is not identified timely and appropriate measures are not taken. Our work emphasizes the requirement of screening intermittently symptomless diabetic patients for diastolic dysfunction through a Doppler echocardiography so that timely action can be taken., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Guria et al.)

This review article aimed to determine the obstetric and maternal outcomes after B-Lynch compression sutures to control atonic postpartum hemorrhage (PPH). This meta-analysis was performed after registering the protocol in the PROSPERO database with the registration number CRD42022355358. Two independent reviewers systematically searched electronic databases and search engines (PubMed, Cochrane Library, and Google Scholar) to retrieve published articles from inception to July 2022. The obstetric and maternal outcomes after the B-Lynch compression suture were computed using the random-effects model in pooled proportion with a 95% confidence interval (CI). Meta-regression analysis and subgroup analysis were performed to explain any source of possible heterogeneity. Quality assessment of the included studies was done using Joanna Briggs Institute (JBI) tools which are critical appraisal tools for systematic reviews and meta-analyses. This meta-analysis included a total of 30 studies involving 1,270 subjects. The pooled proportion of B-Lynch suture alone was 91% (95% CI = 82-97%). The combined proportion of B-Lynch suture plus another compression suture was 1% (95% CI = 0-3%), and the pooled proportion of B-Lynch suture plus vessel ligation was 3% (95% CI = 1-6%). The pooled proportions of PPH controlled and hysterectomies were 94% (95% CI = 91-97%, I 2 = 65.3%) and 7% (95% CI = 4-10%, I 2 = 72.13%), respectively. Therefore, B-Lynch suture (either alone or in combination with other techniques) is a simple and effective measure to control atonic PPH., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Nalini et al.)

Discovery and validation of genetic factors for multifactorial and polygenic disorders like stroke are needed to make progress in precision medicine. Although some traditional risk factors for stroke have been identified, they do not fully explain the pathophysiological mechanism of ischemic stroke. The research of genetic risk factors is becoming increasingly relevant in the understanding of stroke mechanisms and the finding of population-specific therapeutic targets. The methylenetetrahydrofolate reductase (MTHFR) gene is involved in homocysteine metabolism, and a high homocysteine level is a risk factor for stroke. Using a meta-analysis technique, we investigated the link between the MTHFR C677T gene polymorphism and the risk of ischemic stroke. We used the electronic databases PubMed, Medline, Embase, and Google Scholar to find articles in the Journal of Stroke. If heterogeneity was more than 50%, pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model; otherwise, a fixed-effects model was used. A total of 67 case-control studies with 17,704 cases and 21,981 controls met our inclusion criteria. The Asian population was represented by 41 studies, whereas the Caucasian population was represented by 26. Under the recessive model, a gene polymorphism at the 677 location of the MTHFR gene is related to an elevated risk of ischemic stroke (OR: 1.29, 95% CI: 1.22-1.37, P < 0.001). People who have the MTHFR C677T gene polymorphism have a greater risk of stroke than people who do not., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Kumar et al.)

Introduction: Severe preeclampsia can lead to various complications including increased intracranial pressure (ICP) which can be catastrophic but difficult to detect because of variable nonspecific symptoms. Ultrasonography has been used as noninvasive measure to monitor optic nerve sheath diameter (ONSD) as a marker of raised ICP. Effect of MgSO 4 on ICP can modify the management approach, need for additional monitoring, targeting hemodynamic goals, timing of delivery, and choice of anesthesia. We evaluated the effect of MgSO 4 on raised ICP in severely preeclamptic patients using ultrasound-guided ONSD as a surrogate marker of ICP., Methodology: This prospective observational study was conducted after ethical committee approval and written informed consent from patients. Ultrasound-guided ONSD was measured and compared in 47 severe preeclamptic patients before and at 1 h, 4 h, 12 h, and 24 h after starting MgSO 4 therapy. The analysis of data was done by one-way analysis of variance using Statistical Package for the Social Science., Results: Mean ONSD was 5.56 ± 0.30 mm in our study group. ONSD above 5.8 mm was seen in 17 (36.17%) patients and was considered as marker of raised ICP. There was a significant decrease in ONSD after 4 h of administration of MgSO 4 . No significant correlation was observed between mean arterial pressure, serum magnesium level, and ONSD., Conclusion: Ultrasound-guided ONSD measurement can be used as a quick, noninvasive bedside tool in severe preeclamptic patient on MgSO 4 treatment as marker of ICP which help us in determining clinical severity, therapeutic response, and to decide further course of management., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Anesthesia: Essays and Researches.)

Background of the Study: Instrumental activities of daily living (IADL) are activities that are needed to live an independent life. Psychotic disorders are associated with deficits in everyday functioning, causing impairment/disability in activities of daily living. Activities play a crucial role to measure functional health or disability. People with Schizophrenia often present difficulties in social and occupational reintegration that may be associated with problems in performing daily activities, including independent living, education, working, and socializing. Activities of daily living and instrumental activities of daily living (life skills training) including leisure and social skills training intended to reintegrate the patient into the community to lead an everyday life., Aim: The aim of this review was to identify the effect of skill-based interventions on independent functioning in persons with Schizophrenia., Methods: The authors conducted database searches of Google Scholar, PubMed, Science Direct, ProQuest, EBSCO from 1st January 1992 to 31st December 2020. The researcher extracted data, and the quality of included studies was rated by two authors independently. We used the Cochrane Risk of Bias (ROB) tool for assessing the quality of selected studies. The search identified nine studies that met the inclusion criteria with 655 participants. The outcome measure was independent functioning skills., Results: The interventions in the review were multifaceted with different combinations of psychoeducation, cognitive-behavioral methods, training in social skills, and IADL. The interventions resulted in significant improvement in functioning skills and reduction in relapse rates., Conclusion: Results of this review have revealed moderate to strong evidence for skills training, either behavioral or social skills to improve social and independent functioning, reduce caregiver burden, and improve negative symptoms. The review also supported that interventions could be generalized across settings.

Background: Facial area is one of the most frequently injured area of the body, accounting for 23-97% of all facial fractures. Treatments under general anesthesia as those for maxillofacial fractures or infections is a highly complicated and a major challenging task in trismus associated patients. The main culprit in trismus is the increase muscle tone of masticatory muscles which are supplied via the mandibular nerve, blocking which could help increase the mouth opening thus, changing the whole of airway management., Material and Method: A prospective study was done on 50 patients of ASA grade I-II with unilateral mandibular fracture with trismus posted for maxillofacial surgery. Mandibular nerve block was given via extraoral approach with 5 ml of 0.5% bupivacaine using peripheral nerve stimulator to determine the difference in Pre block and Post block mouth opening and the VAS score at 2, 5, 10, 15, 20, 25, and 30 minutes., Results: The Interincisor distance measured Pre block was 1.20 ± 0.32 mm and was significantly increased after 5 mins onwards from the block ( P < 0.005). The VAS score determined Pre block was 5.14 ± 1.37 which significantly decreased just 2 minutes after the application of block ( P < 0.005)., Conclusion: Mandibular nerve block decreases the pain and will aid in the decision making by an anesthetist regarding airway management as it helps in increasing the inter incisor distance significantly. Moreover, given the feasibility and effectiveness of the block it could be included in standard of care protocol for mandibular fracture patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Saudi Journal of Anesthesia.)

Background: Human anatomy instruction is mostly focused on cadaver dissection and prosected specimen examination. Exposure to cadaver dissection can be a stressful experience that may cause a wide variety of symptoms among students of health sciences. To compare and evaluate the effect of in-vitro and in-vivo exposure on cadaveric anxiety, disgust propensity and sensitivity, and attitude toward death and dying among 1 st -year medical and nursing students., Materials and Methods: An open-label randomized trial (matched-control experimental design) was conducted among 127 1 st -year Medical and Nursing students from a selected Institute of National Importance, Bhopal, India during 2015. The participants were divided into an experimental and control group based on matched trait anxiety scores using the Trait Anxiety Inventory. Followed by preassessment, video demonstration with cadaver dissection ( in vitro exposure) was then administered to the experimental group, while the control group had direct exposure to cadaver dissection ( in vivo exposure)., Results: The study showed that there was a statistically significant difference in state anxiety related to cadaver dissection in the experimental group ( P = 0.01). However, video-demonstration of cadaver dissection did not have any effect on disgust propensity and sensitivity and attitude toward death and dying., Conclusion: The findings provided evidence that video-demonstration of cadaver dissection reduced anxiety, although it did not have any effect on disgust and attitudes of death. The dissection hall experience may evoke feelings of anxiety and disgust that need to be addressed through advanced preparedness and coping strategies, especially among medical and nursing students., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Education and Health Promotion.)

Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: to evaluate the effects of intravenous (IV) dexmedetomidine as a pre-medication on clinical profile of bupivacaine spinal anaesthesia in lower abdominal surgeries., Methods: this prospective randomized double blind study was done on 60 patients with ASA grade I/II undergoing lower abdominal surgeries under bupivacaine spinal anaesthesia. They were allocated to group-1 and group-2. Group-1 (control group) received normal saline and group-2 (study group) received IV dexmedetomidine 1 µg/kg over 10 min as premedication. Five minutes after premedication, subarachnoid block (SAB) was given with 3 ml of 0.5% hyperbaric bupivacaine following which sensory and motor blockade, hemodynamic changes, sedation, and complications of the surgery were recorded and this data was analyzed statistically using χ 2 test, corrected χ 2 test, Fisher´s exact test, and test of proportion (Z-test)., Results: the results of the present study showed that in group-2 there was significant decrease in the onset of sensory block, higher level of sensory blockade achieved, less time required to attain highest level of anaesthesia, prolonged time required for 2 dermatomal regression, prolonged duration of sensory blockade, prolonged duration of analgesia, decrease in onset of motor blockade, no significant increase in duration of motor blockade, there was overall hemodynamic stability except for few cases of bradycardia responding to atropine and hypotension responding to mephentramine, adequate and acceptable intraoperative sedation, and significantly less incidence of shivering in perioperative period., Conclusion: IV infusion of dexmedetomidine 1 µg/kg body weight prior to SAB can be recommended to achieve better sensory blockade and adequate hemodynamic stability and sedation., (Copyright: Amit Kumar Choudhary et al.)

The global health crisis caused by the coronavirus pandemic (COVID-19) has brought about previously unimaginable changes to all of health care, including the field of psychiatric rehabilitation. During the pandemic, many issues pertaining to the people with SMI(Severe Mental Illness) was addressed, however, we have not found any studies exploring the impact of pandemic on Activities of daily living. Here we discuss two case reports to furnish the first -hand experience on how online sessions have helped patients to improve their Instrumental Activities of Daily Living (IADL), a component of Activities of Daily Living (ADL). Though the pandemic had an impact on IADL initially in both the patients, with technology facilitated psychiatric rehabilitation both patients improved in areas of managing household chores, cooking, concentration and memory as reported by their caregivers. Family involvement in care and bonding also increased. Online sessions facilitated persons with mental illness to engage in daily activities, created an interest in them to attend the sessions and to translate them in real-time world and increased the involvement of caregivers in training them., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature India Private Limited 2021.)

Context: The context of the study is to compare and find better muscle relaxant between rocuronium and vecuronium for intubation and maintenance under general anesthesia in patients undergoing laparoscopic cholecystectomy., Aims: The aim of the study is to measure intubating condition, hemodynamic changes during intubation and also during maintenance of general anesthesia and to record complications, if any., Settings and Design: A prospective clinical study conducted in the Department of Anesthesiology in tertiary care center., Materials and Methods: A total of 100 patients of the American Society of Anesthesiologists Classes Grade I and II were planned for laparoscopic cholecystectomy were divided into two groups of 50 each. The subjects in the control and study group were put under anesthesia using injection propofol 2.0 mg.kg -1 along with injection vecuronium 0.10 mg.kg -1 and injection propofol 2.0 mg.kg -1 along with injection rocuronium 0.60 mg.kg -1 , respectively. Hemodynamic monitoring and oxygen saturation (SPO 2 ) were recorded at various intervals., Statistical Analysis Used: All the collected data were imported into Microsoft Excel, and the statistical analysis was done by using SPSS 25.0 version., Results: The mean heart rate before and after carboperitoneum at different time intervals and before and after extubation was significantly lower in vecuronium group. The mean systolic blood pressure and mean arterial pressure at 1 and 5 minutes after extubation were significantly more among vecuronium group., Conclusions: Rocuronium is reasonably cardiostable, produces excellent intubation conditions, has a shorter duration of action, and shows minimal cumulative effect., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Anesthesia: Essays and Researches.)

Background and Aims: The pain following total abdominal hysterectomy (TAH), a very commonly performed gynaecological surgery, is usually taken care of by various opioids, non-opioids, regional and peripheral nerve blocks. Erector spinae plane block (ESPB) under ultrasound guidance is a relatively new approach for postoperative analgesia in thoracic and abdominal surgeries. Ultrasound availability and expertise to use it is a limitation at times. The primary aim of this study was to determine the analgesic efficacy of ESPB using peripheral nerve stimulation (PNS) technique in patients undergoing TAH., Methods: A total of 60 American Society of Anesthesiologists physical status I and II female patients were posted for abdominal hysterectomy after obtaining ethical committee clearance in a tertiary care centre. Group I (n = 30) received spinal anaesthesia, whereas Group II (n = 30) received ESPB under peripheral nerve stimulator (PNS) guidance with 20 mL of 0.375% ropivacaine before spinal anaesthesia. Post-operative pain intensity reported using the Visual Analogue Scale (VAS) was considered as the primary outcome. The haemodynamic variables, total duration before the first rescue analgesia, total consumption of tramadol, level of satisfaction regarding analgesia and any complications were considered as secondary outcomes. The data were recorded in an excel sheet, and analysis was performed using the Statistical Package for the Social Sciences version 23.0., Results: VAS score was significantly lower ( P < 0.001) in Group II at 0, 1, 2, 3, 4, 6, 12, 18 and 24 h post-operatively. The total dose of rescue analgesia was significantly reduced in the ESPB group., Conclusion: PNS-guided ESPB is effective in relieving pain in patients undergoing TAH., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Indian Journal of Anaesthesia.)

Background of the Study: Persons with mental illness (PwMI) are prone to weight gain as a side effect of antipsychotics. Health counselling on diet, physical activity, medication adherence, expressed emotions and technology use, by health professionals, can help in managing these side-effects., Aim: The aim of this study was to identify the pre-counselling profile of the subjects such as body mass index (BMI), diet, physical activity, medication adherence, expressed emotions and technology use among PwMI; to attend the Holistic Health Clinic as part of follow-up services in the psychiatry Outpatient Department (OPD) as well as to find correlation and association between the study variables., Methods: The study involved a cross-sectional descriptive design based on convenience sampling. The sample consists of 56 patients who are receiving antipsychotics under symptom control (self-reported) and were overweight. Data were collected with a patient assessment proforma and analysed using SPSS-22., Results: The patients referred to the holistic health counselling (HHC) had abnormal weight and BMI. The mean and SD of weight was 74.48 ± 14.07 and BMI 29.51 ± 5.15. All the participants received counselling on diet, 87.5% on physical activity, 62.5% on sleep hygiene, 55.4% on medication adherence, 8.9% on family emotional climate and only 5.4% on healthy use of technology. Weight has shown significant relation with gender (male = 80.84 ± 17.71, female = 71.09 ± 10.52, t  = -2.52, p  = .015) and near to significant relationship ( χ 2  = 7.685, p  = .053) with educational status., Conclusion: Patients receiving second-generation antipsychotics (SGA) have lesser extra pyramidal side-effects; however, they are more prone to gain weight. Proper screening and counselling during the follow-up visit in the outpatient setting can help in identification, prevention and management of the obesity-related metabolic syndrome and cardiovascular disease (CVD), and motivate them to adopt healthy behaviours.

Background: Percutaneous nephrolithotomy (PCNL) a minimally invasive method for the removal of renal calculi and is associated with significant pain in postoperative period. Conventionally, intravenous opioids, local anesthetic infiltration, and regional blocks (intercostal/paravertebral blocks) have been tried with less efficacy to control postoperative pain. The present study is conducted to assess the effectiveness of erector spinae plane block (ESPB) performed under fluoroscopy guidance for postoperative analgesia during PCNL., Subjects and Methods: After obtaining ethical clearance, the study was conducted on 61 American Society of Anaesthesiologists (ASA) I and II patients aged between 18-65 years admitted for PCNL. Group I ( n = 30) did not receive ESPB while Group II ( n = 31) received ESPB under fluoroscopy guidance and 20 ml of 0.375% ropivacaine was administered after PCNL. Patient-reported pain intensity using visual analogue scale (VAS) was considered as a primary outcome. The hemodynamic variables (heart rate, systolic, diastolic, and mean blood pressure) was considered as a secondary outcome. Statistical analysis was performed using Student's t -test and Mann-Whitney U test. Data analysis was performed using the Statistical Package for the Social Sciences version 23.0., Results: Postoperatively VAS score was significantly lower in Group II at 0, 1, 2, 3, 4, 6, 12, 18, and 24 hours after PCNL ( P < 0.001). Dose of rescue analgesia significantly decreased in Group II compared to Group I., Conclusion: ESPB performed under fluoroscopic guidance is a simple and effective technique and it provides significantly better postoperative pain relief., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Saudi Journal of Anesthesia.)

Background: A number of persons with severe mental illnesses are unable to prepare for, find or keep a job due to factors linked to their illness as well as psychosocial issues., Aim: To test the feasibility of a supported employment programme to help persons with severe mental disorders obtain and sustain employment., Methods: A supported employment programme was developed for persons with severe mental disorders with components of (a) assessment of vocational potential, (b) vocational counselling, (c) networking and liaison with prospective employers, (d) job-related training and placement and (e) continued support for 6 months. Job placement status, social occupational functioning and disability (quantitative data) and benefits of enrolling in the employment programme (qualitative data) were assessed., Results: A total of 40 employers were liaised with for providing job placement and reasonable accommodation. Out of 63 participants recruited into the study, 32 (50.8%) participants were placed in competitive jobs, placement was actively attempted for 17 (27.0%) participants, 7 (11.1%) were referred for skill training and 7 (11.1%) dropped out from the study. The disability score significantly reduced and socio-occupational functioning significantly improved in those who were placed over a period of 6 months., Conclusion: The supported employment programme was found to be feasible as it showed good placement rates and improvement in socio-occupational functioning and disability scores.

Objectives: This study aimed to compare the effects of nitroglycerin (NTG) versus lignocaine spray in blunting the pressor response during direct laryngoscopy and endotracheal intubation., Methods: This study was conducted between January and June 2018 in the Department of Anesthesiology, Teerthankar Mahaveer Medical College, Moradabad, India. A total of 90 elective surgical patients of American Society of Anesthesiologists physical status grades I or II were divided into three groups, comprising two treatment groups and one control group. Patients in the treatment groups received either one puff (1.5 mg/kg) of lignocaine 10% spray or one puff (400 μg) of NTG spray in the oropharynx one minute prior to the induction of anaesthesia. Haemodynamic variables and mean rate pressure product at baseline and one, two, three, four and five minutes post-induction were compared., Results: There was a significant reduction in mean heart rate at 3-5 minutes in both treatment groups compared to the control group ( P <0.050), as well as lower increases in mean arterial pressure at 1-3 minutes ( P <0.050). However, at 2-4 minutes, there was a significantly greater decrease in mean systolic blood pressure in the NTG group compared to both the lignocaine and control groups ( P <0.050). Moreover, a greater decrease in mean rate pressure product response at 1-5 minutes was observed in the NTG group compared to the lignocaine and control groups ( P = 0.001)., Conclusion: The NTG spray was more effective than lignocaine in attenuating blood pressure increases and rate pressure product during elective laryngoscopy and intubation., Competing Interests: CONFLICT OF INTEREST The authors declare no conflicts of interest., (© Copyright 2019, Sultan Qaboos University Medical Journal, All Rights Reserved.)

Background: Dexmedetomidine, a selective alpha 2 (α 2 )-adrenergic receptor agonist, has been used to blunt the hemodynamic response associated with laryngoscopy and tracheal intubation, which is a common concern for the anesthesiologist, especially in high-risk patients and geriatric age group., Aim and Objectives: The current study is to evaluate and compare the effects of different doses of dexmedetomidine in controlling hemodynamic response during tracheal intubation in geriatric patients., Materials and Methods: After getting approval from the Ethical Committee, 90 patients of the American Society of Anesthesiologist Physical Status Classes I and II, aged ≥60 years, were randomly assigned into three groups: Group I (normal saline, n = 30), Group II - dexmedetomidine (0.50 μg/kg, n = 30), and Group III - dexmedetomidine (1.00 μg/kg, n = 30). Dexmedetomidine was infused for 10 min before induction. Data were recorded as before infusion (T0), at the end of infusion (T1), before tracheal intubation (T2), at the moment of tracheal intubation (T3) 5 min after tracheal intubation (T4), and 10 min after tracheal intubation (T5). Modified observer's assessment of alertness/sedation scale score was observed at the time of T0 and T1. All statistical analyses were done using SPSS version 22., Results: Mean systolic blood pressure was statistically significantly ( P < 0.05) more among Group I compared to Group II and III at T2, T3, and T4. Mean heart rate (HR) value was significantly ( P < 0.05) more among Group I compared to Group III from T1 to T5, whereas there was no significant change in HR between Group I and Group II and at T4 and T5 h was comparable in Group II and Group III., Conclusion: This study concluded that more acceptable hemodynamic changes were seen with 0.50 μg/kg dexmedetomidine when compared with 1.0 μg/kg dexmedetomidine during intubation. A lower dose besides being cost-effective is also free of side effects associated with the higher dose of 1 μg/kg dexmedetomidine., Competing Interests: There are no conflicts of interest.

Cilia (flagella) are important eukaryotic organelles, present in the Last Eukaryotic Common Ancestor, and are involved in cell motility and integration of extracellular signals. Ciliary dysfunction causes a class of genetic diseases, known as ciliopathies, however current knowledge of the underlying mechanisms is still limited and a better characterization of genes is needed. As cilia have been lost independently several times during evolution and they are subject to important functional variation between species, ciliary genes can be investigated through comparative genomics. We performed phylogenetic profiling by predicting orthologs of human protein-coding genes in 100 eukaryotic species. The analysis integrated three independent methods to predict a consensus set of 274 ciliary genes, including 87 new promising candidates. A fine-grained analysis of the phylogenetic profiles allowed a partitioning of ciliary genes into modules with distinct evolutionary histories and ciliary functions (assembly, movement, centriole, etc.) and thus propagation of potential annotations to previously undocumented genes. The cilia/basal body localization was experimentally confirmed for five of these previously unannotated proteins (LRRC23, LRRC34, TEX9, WDR27, and BIVM), validating the relevance of our approach. Furthermore, our multi-level analysis sheds light on the core gene sets retained in gamete-only flagellates or Ecdysozoa for instance. By combining gene-centric and species-oriented analyses, this work reveals new ciliary and ciliopathy gene candidates and provides clues about the evolution of ciliary processes in the eukaryotic domain. Additionally, the positive and negative reference gene sets and the phylogenetic profile of human genes constructed during this study can be exploited in future work., (© The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Competing Interests: There are no conflicts of interest.

Amelogenesis imperfecta (AI) is a clinically and genetically heterogeneous group of diseases characterized by enamel defects. The authors have identified a large consanguineous Moroccan family segregating different clinical subtypes of hypoplastic and hypomineralized AI in different individuals within the family. Using targeted next-generation sequencing, the authors identified a novel heterozygous nonsense mutation in COL17A1 (c.1873C>T, p.R625*) segregating with hypoplastic AI and a novel homozygous 8-bp deletion in C4orf26 (c.39&#95;46del, p.Cys14Glyfs*18) segregating with hypomineralized-hypoplastic AI in this family. This study highlights the phenotypic and genotypic heterogeneity of AI that can exist even within a single consanguineous family. Furthermore, the identification of novel mutations in COL17A1 and C4orf26 and their correlation with distinct AI phenotypes can contribute to a better understanding of the pathophysiology of AI and the contribution of these genes to amelogenesis., (© International & American Associations for Dental Research 2016.)

Bardet-Biedl syndrome (BBS; MIM 209900) is a recessive heterogeneous ciliopathy characterized by retinitis pigmentosa (RP), postaxial polydactyly, obesity, hypogonadism, cognitive impairment and kidney dysfunction. So far, 20 BBS genes have been identified, with the last reported ones being found in one or very few families. Whole-exome sequencing was performed in a consanguineous family in which two affected children presented typical BBS features (retinitis pigmentosa, postaxial polydactyly, obesity, hypogonadism and cognitive impairment) without any mutation identified in known BBS genes at the time of the study. We identified a homozygous splice-site mutation (NM&#95;015662.2: c.4428+3A>G) in both affected siblings in the last reported BBS gene, namely, Intraflagellar Transport 172 Homolog (IFT172). Familial mutation segregation was consistent with autosomal recessive inheritance. IFT172 mutations were initially reported in Jeune and Mainzer-Saldino syndromes. Recently, mutations have also been found in isolated RP and Bardet-Biedl-like ciliopathy. This is the second report of IFT172 mutations in BBS patients validating IFT172 as the twentieth BBS gene (BBS20). Moreover, another IFT gene, IFT27, was already associated with BBS, confirming the implication of IFT genes in the pathogenesis of BBS.

Background: Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders., Methods: We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption., Results: We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases., Conclusions: We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease., Trial Registration Numbers: NCT01746121 and NCT02397824., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)