HIV cure: Are we going to make history?

BACKGROUND: At present, combination antiretroviral therapy (cART) is the mainstay for the treatment of people living with HIV/AIDS. cART can suppress the viral load to a minimal level; however, the possibility of the emergence of full-blown AIDS is always there. In the latter part of the first decade of the 21st century, an HIV-positive person received stem cell transplantation (SCT) for treatment of his haematological malignancy. The patient was able to achieve remission of the haematological condition as well as of HIV following SCT. Thorough investigations of various samples including blood and biopsy could not detect the virus in the person's body. The person was declared to be the first cured case of HIV. LITERATURE SEARCH: Over the next decade, a few more similar cases were observed and have recently been declared cured of the infection. A comprehensive search was performed in PubMed, Cochrane library and Google Scholar. Four such additional cases were found in literature. DESCRIPTION & DISCUSSION: These cases all share a common proposed mechanism for the HIV cure, that is, transplantation of stem cells from donors carrying a homozygous mutation in a gene encoding for CCR5 (receptor utilized by HIV for entry into the host cell), denoted as CCR5△32. This mutation makes the host immune cells devoid of CCR5, causing the host to acquire resistance against HIV. To the best of our knowledge, this is the first review to look at relevant and updated information of all cured cases of HIV as well as the related landmarks in history and discusses the underlying mechanism(s).

Understanding water dynamics in Dal Lake: a comprehensive analysis of physiological parameters and seasonal variations.

Maintaining the standard of water quality in an aquatic habitat necessitates continual assessment of its physicochemical properties. The purpose of this study was to evaluate physicochemical properties and to discuss the causes of spatiotemporal variability in key physicochemical parameters at five different locations of Dal Lake. Water samples were collected in four seasons for 3 years (i.e., January 2019-December 2021) to evaluate various physicochemical properties using standard methods. The analysis shows that the macrophytic development has increased due to organic and inorganic load, leading to the Lake's deterioration. The analysis indicates positive and negative correlations among various parameters across five sampling sites. Principal component analysis shows that two components (PC1 and PC2) explain 47.35, 47.54, and 48.11% of the variability in the years 2019, 2020, and 2021, respectively. From 2019 to 2021, the continuous decrease in dissolved oxygen and increased levels of magnesium, conductivity, alkalinity, total hardness, calcium hardness, total phosphorus, and nitrate-nitrogen suggest a trend toward eutrophication in the lake.

The Morel-Lavallée lesionLavalleeLavelle.

BACKGROUND: Trauma patients present to the emergency department with various injuries. Few injuries can be easily missed during the evaluation of polytrauma patients. We report one such rare injury in a trauma patient. CASE REPORT: We report the case of a 67-year-old man who presented to the emergency department with an alleged history of trauma. He reported severe pain in the lower abdomen, right hip, and right thigh. An x-ray study did not reveal any bony injury, and an extended focused assessment with sonography in trauma was also negative. Point-of-care ultrasound of his right thigh revealed the presence of a Morel-Lavallée lesion. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Morel-Lavallée lesions are post-traumatic, closed, degloving injuries that go unnoticed in many polytrauma patients. Emergency physicians should be mindful of this lesion because delay in diagnosis can result in significant complications.

Survival of human periodontal ligament fibroblast cells in Cornisol and HBSS for transportation of avulsed teeth: a comparative ex vivo study.

OBJECTIVE: Viability of periodontal ligament fibroblast cells (PDFC) is one of the key factors in determining the success of replantation of avulsed teeth. Extra-oral time and transport media are closely related to the same. The present study aims to evaluate and compare the efficiency of Cornisol, Hank's balanced salt solution (HBSS) and normal saline in preserving the viability of PDFC. MATERIALS AND METHODS: The human PDFC were isolated from primary culture from freshly extracted human premolars. Effect of Cornisol, HBSS and normal saline on viability of isolated PDFC was assessed using standard MTT assay. The cells were exposed to the experimental solutions (Cornisol/HBSS/normal saline) for varying time points (30 min, 1 h, 24 h, 48 h and 96 h) and viability was determined by colorimetric MTT method by quantifying the amount of formazan crystal formed (optical density). Experiment was performed in triplicates and the data were subjected to statistical analysis. RESULTS: Statistical analysis was performed using the Kruskal-Wallis ANOVA with post hoc Bonferroni's test with a significance level of p value ≤.05. Cornisol ≥ HBSS > saline. CONCLUSION: Cornisol can be used as a storage media for avulsed teeth and is significantly more effective than HBSS in maintaining the periodontal ligament cell viability at tested time intervals.

Real-Time Optical Detection of Isoleucine in Living Cells through a Genetically-Encoded Nanosensor.

Isoleucine is one of the branched chain amino acids that plays a major role in the energy metabolism of human beings and animals. However, detailed investigation of specific receptors for isoleucine has not been carried out because of the non-availability of a tool that can monitor the metabolic flux of this amino acid in live cells. This study presents a novel genetically-encoded nanosensor for real-time monitoring of isoleucine in living cells. This nanosensor was developed by sandwiching a periplasmic binding protein (LivJ) of E. coli between a fluorescent protein pair, ECFP (Enhanced Cyan Fluorescent Protein), and Venus. The sensor, named GEII (Genetically Encoded Isoleucine Indicator), was pH stable, isoleucine-specific, and had a binding affinity (Kd) of 63 ± 6 µM. The GEII successfully performed real-time monitoring of isoleucine in bacterial and yeast cells, thereby, establishing its bio-compatibility in monitoring isoleucine in living cells. As a further enhancement, in silico random mutagenesis was carried out to identify a set of viable mutations, which were subsequently experimentally verified to create a library of affinity mutants with a significantly expanded operating range (96 nM-1493 µM). In addition to its applicability in understanding the underlying functions of receptors of isoleucine in metabolic regulation, the GEII can also be used for metabolic engineering of bacteria for enhanced production of isoleucine in animal feed industries.

Relation of plasma ceramides to visceral adiposity, insulin resistance and the development of type 2 diabetes mellitus: the Dallas Heart Study.

AIMS/HYPOTHESIS: Ceramides are sphingolipids that contribute to insulin resistance in preclinical studies. We hypothesised that plasma ceramides would be associated with body fat distribution, insulin resistance and incident type 2 diabetes in a multi-ethnic cohort. METHODS: A total of 1557 participants in the Dallas Heart Study without type 2 diabetes underwent measurements of metabolic biomarkers, fat depots by MRI and plasma ceramides by liquid chromatography-mass spectrometry. Diabetes outcomes were assessed after 7 years. Associations of body fat and insulin resistance with ceramides at baseline and of ceramides with incident diabetes outcomes were analysed. RESULTS: The cohort had a mean age of 43 years, with 58% women, 45% black participants and a mean BMI of 28 kg/m2. Total cholesterol levels were associated with all ceramides, but higher triacylglycerols and lower HDL-cholesterol and adiponectin were associated only with saturated fatty acid chain ceramides (p < 0.0003). After adjusting for clinical characteristics and total body fat, visceral adipose tissue was positively associated with saturated fatty acid ceramides (per SD, ß = 0.16 to 0.18) and inversely associated with polyunsaturated fatty acid ceramides (ß = -0.14 to -0.16, p < 0.001 for all). Lower-body subcutaneous fat showed an opposite pattern to that for visceral fat. HOMA-IR was positively associated with saturated (ß = 0.08 to 0.09, p < 0.001) and inversely with polyunsaturated ceramides (ß = -0.06 to -0.07, p < 0.05). Ceramides were not associated with incident type 2 diabetes after adjustment for clinical factors. CONCLUSIONS/INTERPRETATION: Plasma ceramides demonstrate a biologically complex relationship with metabolic and imaging indicators of dysfunctional adiposity. The role of ceramides in a shared pathway of metabolic dysfunction linking visceral adiposity and insulin resistance requires further investigation.

Oral vs. injected: which vitamin D boost works best for low levels?

OBJECTIVES: Vitamin D is essential for maintaining bone and mineral balance. This study aims to identify the most effective route for achieving optimal vitamin D levels (≥30 ng/mL) to support bone and mineral health. METHODS: In this open-label randomized trial, 132 participants aged 18-60 with initial serum vitamin D levels below 30 ng/mL were divided into three intervention groups: daily 800 I.U. oral tablet (Group A), weekly 60,000 I.U. oral sachet (Group B), and monthly 300,000 I.U. intramuscular injection (Group C). The study assessed changes in their serum vitamin D levels at six and 12 weeks. RESULTS: The monthly intramuscular (IM) group consistently had the highest mean vitamin D levels at six weeks 38.38(±9.953) (p<0.002) and 12 weeks 48.15(±7.71) (p<0.001). Vitamin D insufficiency was reduced to 34.8 % at six weeks (p=0.434) and 6.8 % at 12 weeks (p=0.002). Notably, 100 % of the monthly IM group achieved vitamin D sufficiency at 12 weeks. CONCLUSIONS: The monthly IM route demonstrated superior effectiveness compared to tablets and sachets at both the 6-week and 12-week points. A significantly larger number of monthly IM participants achieved vitamin D sufficiency compared to the other groups.

Effect of cannabinoids in mild-to-moderate cases of Crohn's disease as compared to placebo: a systematic review and meta-analysis of randomised controlled trials.

INTRODUCTION: In view of limited treatment options (those too may fail) for Crohn's disease, cannabinoids have been tried as a therapeutic. However, their efficacy is not unequivocally established. This systematic review and meta-analysis was planned to pool data from randomised controlled trials (RCTs) evaluating effect of cannabinoids in Crohn's disease with an intention to take this uncertainty away. CONTENT: Following literature search in Medline, EMBASE, Scopus and Google Scholar databases, RCTs assessing the effect of cannabinoids on mild-to-moderate Crohn's disease in adults were included. Crohns' disease activity index (CDAI), QoL (Quality of life), number participants achieving full remission and serum CRP at eight weeks of treatment were the outcomes considered for meta-analysis. Quality of studies was assessed using Cochrane's RoB2 tool. Random effect model was applied for meta-analysis. Heterogeneity was assessed by Cochrane 'Q' statistics and I2 test. Sensitivity analysis was performed to identify the major contributor(s) to heterogeneity and assess robustness of the results. SUMMARY: Risk of bias for the four included studies varied from 'low' to 'some concern'. Overall effect estimate (SMD -0.92; 95 % CI -1.80, -0.03) indicated a statistically significant effect of cannabinoids as compared to control (p<0.05) on CDAI score. Effect of cannabinoids on rest of the outcome parameters was comparable to that of placebo. Magnitude of heterogeneity for different outcome parameters ranged from 'low' to 'substantial'. OUTLOOK: Cannabinoids were superior to placebo for favourably affecting the disease severity in terms of CDAI score. However, no statistically significant difference was found between the two for improving QoL, causing full disease-remission and reducing inflammatory markers. The results must be interpreted with caution in view of relatively high heterogeneity among the studies.

Faculty Perception of Scenario-Based MCQs, SAQs, and MEQs in Medical Education at an Apex Institute.

Purpose: This study explores the current knowledge and overall awareness of the faculty at an Apex institute about the use and difficulties of scenario-based multiple-choice questions (SB-MCQs), short-answer questions (SB-SAQs), and modified essay questions (SB-MEQs) in the assessment of the undergraduate and postgraduate students. Objectives: To assess faculty perception of awareness and use of SB-MCQs, SB-SAQs, and SB-MEQs and to understand the challenges encountered while designing scenario-based questions (SBQs) and the ways to overcome them. Study Procedure: The tool used for data collection was a Google form questionnaire designed with a total of 16 questions-12 Likert-scale format items and four open-ended questions. The quantitative data collected as a response to close-ended questions was analyzed by descriptive statistics and percentage values. For qualitative data, thematic analysis was done for open-ended questions. Conclusion: The study showed that the faculty has the motivation and agreeability to switch over from traditional questions to scenario-based questions but constant training in the form of regular faculty development programs and workshops is required for its effective implementation. On the administrative level, challenges like lack of sufficient faculty and proper inter-departmental integration for designing scenarios must be addressed. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-024-02052-6.

Mechanically controlled multifaceted dynamic transformations in twisted organic crystal waveguides.

This study introduces mechanically induced phenomena such as standing, leaning, stacking, and interlocking behaviors in naturally twisted optical waveguiding microcrystals on a substrate. The microscale twisted crystal self-assembled from 2,4-dibromo-6-(((2-bromo-5-fluorophenyl)imino)methyl)phenol is flexible and emits orange fluorescence. Mechanistic analysis reveals the strain generated by the intergrowing orientationally mismatched nanocrystallites is responsible for the twisted crystal growth. The crystal's mechanical flexibility in the perpendicular direction to (001) and (010) planes can be attributed to intermolecular Br···Br, F···Br, and π···π stacking interactions. Through a systematic process involving step-by-step bending and subsequent optical waveguiding experiments at each bent position, a linear relationship between optical loss and mechanical strain is established. Additionally, the vertical standing and leaning of these crystals at different angles on a flat surface and the vertical stacking of multiple crystals reveal the three-dimensional aspects of organic crystal waveguides, introducing light trajectories in a 3D space. Furthermore, the integration of two axially interlocked twisted crystals enables the coupling of polarization rotation along their long axis. These crystal dynamics expand the horizons of crystal behavior and have the potential to revolutionize various applications, rendering these crystals invaluable in the realm of crystal-related science and technology.

Surgical Site Infection in Laparoscopic Hysterectomy versus Abdominal Hysterectomy in Gynecological Disease(s): An Overview.

Objective: Surgical site infection (SSI) is an unsettled complication seen in any surgery. The aim of this study is to assess the rate of postoperative SSIs between total laparoscopic hysterectomy (TLH) and total abdominal hysterectomy (TAH). Can the rate of SSI be reduced with the use of a laparoscopic mode of hysterectomy over abdominal? Materials and Methods: It was a retrospective comparative study. The study was conducted in the obstetrics and gynecology department at a tertiary care center from June 2016 to March 2020. A total of 300 patients who underwent hysterectomy either via laparoscopic or abdominal route were included in the study. They were subdivided into two groups: a total of 167 underwent TLH (Group 1) and 133 had TAH (Group 2). The results were compared. It included the age and body mass index of the patient, indication of surgery, size of the uterus, intraoperative blood loss, postoperative SSIs, duration of hospital stay, and readmission rates. Results: It was found a high rate of SSI in TAH (82.4% vs. 17.6%, P < 0.001, Cramer's V-0.18), the operative time taken (75 ± 25 min vs. 128 ± 52 min, P < 0.001), and the mean blood loss during TLH (110 ± 30 ml vs. 160 ± 116 ml, P < 0.001) was found significant for patients. The hospital stay after TLH was found to be significantly shorter (4 ± 2.47 days vs. 7 ± 2.43, P < 0.001). Conclusion: TLH has improved the psychological, physical, and financial burden on the health care department. Thus, it has proved a preferred route over TAH.

An integrative approach for management of post-traumatic dorsal foot wounds - A case report.

Crush injuries to the foot have become increasingly prevalent in contemporary settings, primarily arising from incidents such as the impact of large objects falling onto the foot or involvement in traffic accidents. The complexity of treating these injuries is compounded by the intricate anatomy of the foot. In specific scenarios, the implementation of an integrated management approach could prove advantageous. In this report, we depict the case of a 23-year-old male who visited the Shalya OPD with a wound on his left foot caused by trauma. The wound covered the medial portion of the foot, involving the dorsal area, and measured roughly 20 cm by 9 cm and was unable to walk. We successfully managed the case by adopting an integrative approach. The Ayurvedic treatment included Panchavalkala kashaya for wound irrigation, as well as oral administration of Amalaki rasayana, Triphala guggulu, Shatavari churna and Ashwagandha churna. Jatyadi taila was topically applied. For the first seven days, in addition to these ayurvedic medications, we also employed analgesics and antibiotics to treat infection and pain. To accomplish early closure, we employed a split-thickness skin graft after sufficient granulation tissue had appeared. The wound was completely healed within three months and the patient was able to walk freely without any support. The combined approach yielded a promising result in this case.

Lesions Misdiagnosed as Endodontic Pathosis: A Narrative Review.

In daily practice, clinicians come across certain radiographic abnormalities which may or may not be asymptomatic. This abstract discusses radiographic abnormalities encountered by clinicians in daily practice, some of which resemble endodontic lesions. Prompt attention is crucial as these lesions can be benign or malignant. The article emphasizes the importance of differential diagnosis for accurate identification of periapical pathosis.

Unleashing the therapeutic role of cannabidiol in dentistry.

Cannabidiol (CBD) found in Cannabis sativa is a non-psychoactive compound which is capable of binding to CB1 and CB2 receptors. CBD has recently gained interest in dentistry although it has not been explored sufficiently yet. The therapeutic effects of CBD include anti-inflammatory, analgesic, antioxidant, biological and osteoinductive properties. The aim of this review is to highlight these effects with respect to various oral conditions and shed light on the current limitations and prospects for the use of CBD in maintaining oral health.

Risk of Congenital Anomalies with Dolutegravir-Based Anti-retroviral Regimens: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: Dolutegravir has been used as a first-line anti-human immunodeficiency virus drug because of its better efficacy compared with other counterpart medicines. However, making a unanimous decision on its use during pregnancy has become difficult for stakeholders following congenital anomalies reported with its use. The objective of this systematic review and meta-analysis was to study the risk of congenital anomalies in newborns exposed to dolutegravir-based-regimens compared with those exposed to non-dolutegravir-based regimens during the antenatal period. METHODS: An extensive literature search was performed in MEDLINE (through PubMed), EMBASE, Cochrane Database of Systematic Reviews, Google Scholar, and ClinicalTrials.gov until 30 November, 2023. Studies reporting data on congenital anomalies following antenatal use of dolutegravir were included. Risk of bias for randomized controlled trials, non-randomized controlled trials, and observational studies was assessed using RoB2, ROBINS-I, and ROBINS-E tools, respectively. A meta-analysis was performed in 'RevMan 5.4.1' using a random-effects model. Heterogeneity was assessed by the 'Q' statistic and I2 value. A sensitivity analysis was performed for higher heterogeneity/high-risk studies. The study protocol was registered in PROSPERO [CRD42023446374] a priori. RESULTS: Of 26 eligible studies, 12 (six randomized controlled trials and six observational studies with a pooled sample of 32,617) were included in a meta-analysis and 14 in a qualitative synthesis only. The meta-analysis does not show a statistically significant difference in the risk of congenital anomalies between newborns exposed antenatally to dolutegravir-based regimen(s) and those exposed to non-dolutegravir-based regimens [risk ratio 1.10; 95% confidence interval 0.79-1.53; p = 0.59]. Heterogeneity was moderate (I2 = 47%). Pooled results for randomized controlled trials and observational studies separately and the sensitivity analysis for heterogeneity provided similar results. CONCLUSIONS: The risk of congenital anomalies was not significantly different between dolutegravir-based regimens and non-dolutegravir-based-regimens in newborns exposed during their antenatal period.

Guarding Our Guardians: Navigating Adverse Reactions in Healthcare Workers Amid Personal Protective Equipment (PPE) Usage During COVID-19.

The widespread utilization of personal protective equipment (PPE) during the COVID-19 pandemic has been crucial for reducing transmission risk among healthcare workers (HCWs) and the public. However, the extensive use of PPE has brought about potential adverse reactions, particularly among HCWs. This study aims to investigate the prevalence and characteristics of adverse skin reactions associated with PPE use among different categories of HCWs, including faculty, residents, and nursing officers (NOs), in a dedicated tertiary care COVID-19 hospital. The study design was a hospital-based cross-sectional analytical study conducted over one month, involving a total of 240 participants. The participants were required to complete a pre-tested semi-structured questionnaire that covered demographic information, PPE-related data, preventive measures, observed reactions, and self-management strategies. Results indicated that adverse skin reactions were common among HCWs, with reactions reported by all participants. The most commonly used PPE included N95 masks, goggles, gloves, face shields, isolation gowns, and medical protective clothing. Excessive sweating (60% residents, 21.1% NOs, and 16.25% faculties), facial rash, dry palms (>70% of HCWs), and itching were among the most prevalent adverse reactions. Urticarial lesions (28.5% among NOs), pressure marks and pain (100% on the cheek among all HCWs), fungal infections (18.5% among residents at the web space of fingers), and skin breakdown were also reported. Factors such as age, gender, pre-existing skin problems, and oily/acne-prone skin history were found to be significantly associated with adverse skin reactions. In conclusion, the findings highlight the common adverse reactions reported by HCWs during the use of different PPEs. Certain steps taken by HCWs for the prevention of adverse reactions due to PPE emphasize the importance of tailored preventive measures and strategies to mitigate these adverse reactions, such as proper PPE selection, well-fitting equipment, regular breaks, and appropriate skincare practices. These insights contribute to the development of guidelines for optimal PPE usage and support the well-being of HCWs in their essential roles.

Utilizing a Fe3O4 Magnetite Nanoparticle for Anode Modification in a Microbial Desalination Cell to Treat Saltwater.

The microbial desalination cell (MDC) is a bio-electrochemical system that exhibits the ability to oxidize organic compounds, produce energy, and decrease the saline concentrations within the desalination chamber. The selective removal of ions from the desalination chamber is significantly influenced by the anion and cation exchange membranes. In this study, a three-chamber microbial desalination cell was developed to treat seawater using a synthesize Fe3O4 magnetite nanoparticle (MNP)-modified anode. The impact of different performance parameters, such as temperature, pH, and concentrations of NPs, has been investigated in order to assess the performance of three-chamber MDCs in terms of energy recovery and salt removal. The evaluation criteria of the system included multiple factors such as chemical oxygen demand (COD), Coulombic efficiency (CE), desalination efficiency, as well as system aspects including voltage generation and power density. The highest COD% removal efficiency was 74% at 37 °C, pH = 7, and 30 g/L salt concentration with an optimized NPs concentration of 2.0 mg/cm2 impregnated on anode. The maximum Coulombic efficiency was 10.3% with the maximum power density of 4.3 W/m3. The effect of the nanoparticle concentration impregnated on the anode was clarified by the primary factor of analysis. This research has revealed consistent patterns in the enhancement of voltage generation, COD, and Coulombic efficiencies when incorporating higher concentrations of nanoparticles on the anode at a certain point.

Large Vaginal Hematoma in a Puerperium Patient: Treating a Delayed Diagnosis & Management Caused by an Incomplete Clinical Examination.

Here, we report a case where the lack of pelvic examination in a puerperium patient led to a delay in diagnosis and appropriate management of a large posterior vaginal wall hematoma for about a month. The patient had a history of difficult vaginal breech delivery of a macrosomic asphyxiated baby 28 days prior, following which, she started having gradually increasing distension of the abdomen, inability to void urine and pass stools by herself, and a history of fever on and off. Her family members took her to a private hospital for a consultation, where she was examined and assessed. However, a pelvic examination was not done. A CT scan of the abdomen and pelvis showed a large organized hematoma of size 13.6cm×11.1cm×10.5cm with a volume of 802 ml in the pouch of Douglas. Following this report, diagnostic laparoscopy was done on day 10 of puerperium where a large hematoma was seen beneath the peritoneum in the pouch of Douglas without any intraperitoneal collection. As the hematoma was not seen to be expanding, conservative management was done with 5 units of blood transfusion and antibiotic coverage, and the patient was discharged. However, the patient's symptoms were not relieved due to which she presented to us on day 28 of puerperium with the same symptoms. On pelvic examination, purulent, foul-smelling discharge was present in the vagina, and a huge tense bluish bulge was seen in the posterior vaginal wall more towards the right side obliterating the whole vagina. After taking informed consent and with proper pre-operative preparations of laparotomy, the hematoma was drained vaginally, and approximately 1300 ml of blood and clots were removed, following which, the patient had a speedy recovery and relief of her symptoms.