Outcomes from the International Society of Nephrology Hemolytic Uremic Syndromes International Forum.

Hemolytic uremic syndromes (HUSs) are a heterogeneous group of conditions, only some of which are mediated by complement (complement-mediated HUS). We report the outcome of the 2023 International Society of Nephrology HUS International Forum where a global panel of experts considered the current state of the art, identified areas of uncertainty, and proposed optimal solutions. Areas of uncertainty and areas for future research included the nomenclature of HUS, novel complement testing strategies, identification of biomarkers, genetic predisposition to atypical HUS, optimal dosing and withdrawal strategies for C5 inhibitors, treatment of kidney transplant recipients, disparity of access to treatment, and the next generation of complement inhibitors in complement-mediated HUS. The current rationale for optimal patient management is described.

Dura-based automated vault expansion remodelling (DAVE-R): automated planning of volume expansion in fronto-orbital advancement for trigonocephaly.

Cranial vault remodelling for craniosynostosis aims to increase intracranial volume to facilitate brain growth, avoid the development of raised intracranial pressure and address cosmesis. The extent of vault expansion is predominantly limited by scalp closure and reconstruction technique. Virtual surgical planning tools have been developed to predict post-operative changes and guide expansion. We present a validation study of a novel 'Dura-based Automated Vault Expansion-Remodeling' (DAVE-R) model to guide pre-operative planning for fronto-orbital advancement and remodelling (FOAR). METHODS: Patients with trigonocephaly who underwent FOAR with pre- and post-operative imaging from 2018 to 2020 were identified from a prospectively maintained database. Post-operative scans, normative atlas and whole brain parcellation were registered to the pre-operative images to quantify the change in intracranial volume and morphology (utilising measurement of fronto-orbital advancement and bifrontozygomatic distance) compared to that predicted by the DAVE-R model. RESULTS: Ten patients were included. The DAVE-R model predicted bifrontozygomatic distances of 92.0 + / - 5.14 mm (mean + /SD), which closely matched the post-operative results of 92.7 + / - 6.02 mm (mean + / - SD); (t(d.f. 9) = -0.306, p = 0.77). The fronto-orbital advancement predicted by the DAVE-R method was 11.5 + / - 1.96 mm (mean + / - SD) which was significantly greater than 8.6 + / - 2.94 mm (mean ± SD); (t(d.f. 9) = 3.137, p = 0.01) achieved post-operatively. CONCLUSIONS: We demonstrate that the DAVE-R model provides an objective means of extracting realistic surgical goals in patients undergoing FOAR for trigonocephaly that closely correlates with post-operative outcomes. The normative dural model warrants further study and validation for other forms of craniosynostosis correction.

Occupational heat stress and its health impacts- an overview of research status and need for further research in Southeast Asia with special emphasis on mitigation strategies in North East India.

The Intergovernmental Panel on Climate Change, IPCC predicts that hot seasons will get even hotter due to global climate change. There exists a critical dependence of human metabolic processes on temperature. Changes in thermal balance therefore, have an adverse effect on health because they raise body temperature, cause excessive sweating, and accelerate the rate of dehydration. Different nations and professional groups use different techniques to measure heat strain. This paper aims to review previous research conducted in the area of heat strain due to heat exposure among workers in Southeast Asia and also to profile mitigation strategies in North East India. Studies conducted between the years 2011 to 2023 in the evaluation of the health impacts of occupational heat stress were searched systematically using several sources of databases like PubMed, Google Scholar, Science Direct, Web of Science, Scopus, etc. It was noted that a greater proportion of previous research on evaluating physiological effects was carried out in controlled environments as opposed to real-world field settings. While such studies give us valuable insights into the relationship, applying the same methodology in the workplace may not be feasible. In India, very few research has been carried out on workplace heat stress, and even fewer have been done in North East India using physiological indicators. North East India is also affected by global climate change leading top more hotter days than before. The region of Northeast India, particularly Guwahati (Assam), has recently seen extreme heat waves during the sweltering summer months. With less literature available in this geographical location, studies with actual field-based settings are much needed to understand the occupational health impacts in this region. This review can formulate a suitable methodology for assessing the health impacts in working environment. This can also help the local health professionals to recognize the heat strain parameters that are acceptable worldwide, and use as pertinent indicators to scrutinize worker's health and develop preventive agendas as climate change advances.

Second-line drug-resistant TB and associated risk factors in Karakalpakstan, Uzbekistan.

BACKGROUND: Drug-resistant TB (DR-TB) remains a major public health threat. In 2022, Uzbekistan reported 2,117 cases of DR-TB, with 69% tested for fluoroquinolone resistance. Limited information is available on the prevalence of resistance to bedaquiline, linezolid, and fluoroquinolone, which are key components of the all-oral treatment regimen for rifampicin-resistant TB in Uzbekistan. METHODS: A retrospective study was conducted using extensive programmatic data from 2019 to 2023 in Uzbekistan. We assessed second-line drug-resistant TB (SLDR-TB) rates using phenotypic drug susceptibility testing (pDST). Demographic and clinical characteristics associated with SLDR-TB were analysed using multivariable logistic regression models based on the Allen-Cady approach. RESULTS: In total, 2,405 patients with TB who had undergone pDST were included (median age 40 years, 47% female). The overall SLDR-TB resistance rate was 24% (95% CI 22-26). Prevalence of resistance to bedaquiline, linezolid, moxifloxacin, levofloxacin, and amikacin were respectively 3.1%, 0.8%, 15%, 13%, and 12%. Risk factors for SLDR-TB were resistance to rifampicin and/or isoniazid, exposure to clofazimine, retreatment status, contact with drug-susceptible TB case or DR-TB case, and diabetes. CONCLUSIONS: The high prevalence of SLDR-TB is of major concern, emphasising the need for baseline pDST in RR-TB treatment. Identified risk factors can aid early detection of at-risk individuals and inform clinical practice.

CONTEXTE: La TB résistante aux médicaments (DR-TB) reste une menace majeure pour la santé publique. En 2022, l'Ouzbékistan a signalé 2 117 cas de DR-TB, dont 69% ont été testés pour la résistance aux fluoroquinolones. Les informations sur la prévalence de la résistance à la bédaquiline, au linézolide et aux fluoroquinolones, qui sont des composants clés du traitement entièrement oral de la TB résistante à la rifampicine en Ouzbékistan, sont limitées. MÉTHODES: Une étude rétrospective a été menée en utilisant des données programmatiques exhaustives de 2019 à 2023 en Ouzbékistan. Nous avons évalué les taux de TB résistante aux médicaments de deuxième ligne (SLDR-TB, pour l'anglais, « second-line drug-resistant TB ¼) en utilisant des tests de sensibilité phénotypique aux médicaments (pDST). Les caractéristiques démographiques et cliniques associées à la SLDR-TB ont été analysées à l'aide de modèles de régression logistique multivariés basés sur l'approche Allen-Cady. RÉSULTATS: Au total, 2 405 patients atteints de TB ayant subi un pDST ont été inclus (âge médian de 40 ans, 47% de femmes). Le taux global de résistance à la SLDR-TB était de 24% (CI à 95% 22­26). La prévalence de la résistance à la bédaquiline, au linézolide, à la moxifloxacine, à la lévofloxacine et à l'amikacine était respectivement de 3,1%, 0,8%, 15%, 13% et 12%. Les facteurs de risque de SLDR-TB comprenaient la résistance à la rifampicine et/ou à l'isoniazide, l'exposition à la clofazimine, le statut de retraitement, le contact avec un cas de TB sensible aux médicaments ou de DR-TB, et le diabète. CONCLUSIONS: La prévalence élevée de la SLDR-TB est une source de préoccupation majeure, soulignant la nécessité de réaliser des pDST de base dans le traitement de la TB résistante à la rifampicine. Les facteurs de risque identifiés peuvent aider à la détection précoce des individus à risque et à informer la pratique clinique.

Yield of TB screening in prisons in Tajikistan.

BACKGROUND: The rate of TB in prison institutions is estimated to be 23 times higher than in the general population. Limited documentation exists regarding TB screening in Tajikistan's prisons. This study aims to report findings from a TB screening conducted in prison facilities in Tajikistan. METHODS: A systematic TB screening was conducted between July 2022 and September 2023, following a locally adapted algorithm based on WHO recommendations. The screening yield was calculated as the proportion of confirmed TB cases, with categorical variables compared using a χ2 test. RESULTS: A total of 7,223 screenings were conducted, identifying 31 TB cases, including 17 drug-susceptible TB cases, eight drug-resistant TB cases, and six clinically diagnosed cases. The overall screening yield was 0.43%. Notably, the screening yield was 3.4% among individuals with at least one TB symptom and 0.03% among those without TB symptoms (P < 0.001). CONCLUSION: The identified rate of TB in these prisons is five times higher than in the general population. Symptomatic individuals had a higher likelihood of TB diagnosis, and using chest X-rays significantly improved screening yield. We recommend increasing the capacity for chest X-ray testing to enhance TB prevention and control within prison settings.

CONTEXTE: On estime que le taux de TB dans les établissements pénitentiaires est 23 fois plus élevé que dans la population générale. Il existe peu de documentation sur le dépistage de la TB dans les prisons du Tadjikistan. Cette étude vise à rendre compte des résultats d'un dépistage de la TB mené dans des établissements pénitentiaires au Tadjikistan. MÉTHODES: Un dépistage systématique de la TB a été réalisé entre juillet 2022 et septembre 2023, selon un algorithme adapté localement et basé sur les recommandations de l'OMS. Le rendement du dépistage a été calculé comme la proportion de cas confirmés de TB, avec des variables catégorielles comparées à l'aide d'un test χ2. RÉSULTATS: Au total, 7 223 dépistages ont été effectués, permettant d'identifier 31 cas de TB, dont 17 cas de TB sensible aux médicaments, 8 cas de TB résistante aux médicaments et 6 cas diagnostiqués cliniquement. Le rendement global du criblage était de 0,43%. Notamment, le rendement du dépistage était de 3,4% chez les personnes présentant au moins un symptôme de la TB et de 0,03% chez celles ne présentant pas de symptômes de la TB (P < 0,001). CONCLUSION: Le taux de TB identifié dans ces prisons est cinq fois plus élevé que dans la population générale. Les personnes symptomatiques avaient une probabilité plus élevée d'être diagnostiquées comme atteintes de TB, et l'utilisation de radiographies pulmonaires améliorait considérablement le rendement du dépistage. Nous recommandons d'augmenter la capacité de dépistage par radiographie thoracique afin d'améliorer la prévention et le contrôle de la TB en milieu carcéral.

A 10-year review of isoniazid-resistant TB management in Uzbekistan 2009-2020.

BACKGROUND: Isoniazid (INH, H) resistance is the most common drug-resistant TB pattern, with treatment success rates lower than those in drug-susceptible TB. The WHO recommends a 6-month regimen of rifampicin (RIF, R), ethambutol (EMB, E), pyrazinamide (PZA, Z), and levofloxacin (Lfx) (6REZLfx) for INH-resistant, RIF-susceptible TB (HRRS-TB). Uzbekistan has a high burden of TB (62/100,000 population) and multidrug-resistant TB (12/100,000 population). METHODS: We conducted a retrospective, descriptive study of microbiologically confirmed HRRS-TB using routinely collected programmatic data from 2009 to 2020. RESULTS: We included 854 HRRS-TB cases. Treatment success was 80.2% overall. For REZLfx, the treatment success rate was 92.0% over a short treatment duration, with no amplifications to RIF or second-line anti-TB drug resistance. We documented 46 regimens with REZLfx plus linezolid (success 87.0%) and 539 regimens using kanamycin or capreomycin (success 76.6%). We identified 37 treatment failures (4.3%), 30 deaths (3.5%), 25 resistance amplifications (2.9%), including eight to RIF (0.9%), and 99 lost to follow-up (LTFU) cases (11.6%). Unsuccessful outcomes were more common with older age, diabetes, chest X-ray cavities, smear positivity, smear-positive persistence, and male sex. LTFU was more common with injection-containing regimens. CONCLUSIONS: REZLfx is a safe and effective first-line treatment for INH-resistant, RIF-susceptible TB. Treatment success was lower and LTFU was higher for injection-containing regimens.

CONTEXTE: La résistance à l'isoniazide (INH, H) est la forme de TB pharmacorésistante la plus courante, avec des taux de réussite thérapeutique inférieurs à ceux de la TB pharmacosensible. L'OMS recommande un traitement de six mois à base de rifampicine (RIF, R), d'éthambutol (EMB, E), de pyrazinamide (PZA, Z) et de lévofloxacine (LFx) (6REZLfx) pour la TB résistante à l'INH et sensible au RIF (HRRS-TB). En Ouzbékistan, la prévalence de la TB est élevée, avec un taux de 62 cas pour 100 000 habitants, ainsi que de la TB multirésistante, avec un taux de 12 cas pour 100 000 habitants. MÉTHODES: Une étude rétrospective et descriptive de la HRRS-TB confirmée microbiologiquement a été réalisée en utilisant des données programmatiques collectées de manière routinière de 2009 à 2020. RÉSULTATS: Nous avons inclus 854 cas de HRRS-TB. Le taux de réussite du traitement global était de 80,2%. Pour le traitement avec REZLfx, le taux de réussite était de 92,0% sur une courte durée, sans résistance au RIF ni aux médicaments antituberculeux de deuxième ligne. Nous avons observé 46 schémas thérapeutiques associant REZLfx et linézolide avec un taux de réussite de 87,0%, ainsi que 539 schémas thérapeutiques utilisant la kanamycine ou la capréomycine avec un taux de réussite de 76,6 %. Nous avons enregistré 37 échecs thérapeutiques (4,3%), 30 décès (3,5%), 25 cas de résistance amplifiée (2,9%), dont huit au RIF (0,9%), et 99 cas de perte de suivi (LTFU, pour l'anglais « loss to follow-up ¼) (11,6%). Les échecs étaient plus fréquents chez les patients âgés, diabétiques, présentant des cavités à la radiographie thoracique, un frottis positif persistant et de sexe masculin. La prolongation de la durée d'utilisation était plus fréquente avec les schémas contenant des injections. CONCLUSIONS: REZLfx est un traitement de première intention sûr et efficace contre la TB résistante à l'INH et sensible aux RIF. Le succès du traitement était plus faible et le nombre de LTFU était plus élevé pour les schémas contenant des injections.

Inclusivity of patients in early phase breast cancer clinical trials.

INTRODUCTION: Studies have shown that certain groups of patients are underrepresented in clinical trials including non-Caucasian ethnicity, poor fluency in English, low socioeconomic status, older age, neurodivergence, and large Body Mass Index (BMI). There is a need to ensure adequate representation of these groups so that the results of any trial accurately reflect the population. The aim of this study was to review the pathway of patients recruited into two early phase breast cancer clinical and determine the inclusivity of patients from the aforementioned sub-groups. METHODS: The Breast Cancer Research Database was reviewed, and the characteristics of all patients who were screened for eligibility in two early phase clinical trials was examined. The English Indices of Deprivation was used to populate the Index of Multiple Deprivation (IMD) for each patient using their postcode. RESULTS: In total, 392 patients were eligible to participate, between September 2020 to May 2023. Of these, 144 (36.7 %) were recruited to these two trials. In all, 100 % of patients eligible for these trials were approached and screened for participation. Eligible patients had a mean age of 53.5 years. Recruited patients were younger on average than those not recruited (49.1 years vs 56.0 years, p<0.0001). Only one recruited patient required an interpreter, compared with 24 (9.7 %%) of those who were not recruited (p<0.001). There was no difference in the IMD (p=0.38), BMI (p=0.34) and neurodiversity (p=0.10) between patients recruited into clinical trials and those who were not. CONCLUSION: Older age and poor fluency in the English language remain barriers to participation in early-phase clinical trials despite implementing a clear pathway to trial recruitment. There is a pressing need to address these barriers by raising awareness, improve appropriate training and providing comprehensive trial information to patients in the language of their choice.

Anatomical and Functional Evaluation of Modified Abbe-McIndoe Vaginoplasty at a Tertiary Care Hospital.

BACKGROUND: Mayer-Rokitansky-Kuster-Hauser (MRKH) Syndrome, the second important cause of primary amenorrhea, is characterized by complete mullerian agenesis in the presence of normal karyotype and normal functioning ovaries. Incidence is one in 4500 females. Treatment options include surgical and non-surgical methods. Surgical treatment by creating a neovagina between bladder and rectum is preferred as it gives immediate results. AIM: To evaluate the anatomical and functional outcomes of modified vaginoplasty procedures conducted in our institution. METHODS: An ambispective cohort study was conducted in the Department of Obstetrics and Gynaecology, at a tertiary care hospital and included 10 cases of MRKH syndrome, who underwent surgical treatment in our department. Postoperative outcome was noted. Sexual function was evaluated using the Female Sexual Function Index (FSFI) score. RESULTS: The mean duration of surgery was 40 minutes. The average blood loss during surgery in patients undergoing vaginoplasty was 60 ml. The mean length of the neovagina as measured 1 month after surgery was 7.9 cms. FSFI score was >30 in eight patients. Two patients were lost to follow-up. CONCLUSION: Modified McIndoe vaginoplasty is a simple, safe, and cost-effective procedure in the hands of experts. Only mature patients willing to follow the instructions and planning to get married soon should undergo this surgery.

Single-Atomic Co-N4 Sites with CrCo Nanoparticles for Metal-Air Battery-Driven Hydrogen Evolution.

Designing highly active and robust earth abundant trifunctional electrocatalysts for energy storage and conversion applications remain an enormous challenge. Herein, we report a trifunctional electrocatalyst (CrCo/CoN4@CNT-5), synthesized at low calcination temperature (550 °C), which consists of Co-N4 single atom and CrCo alloy nanoparticles and exhibits outstanding electrocatalytic performance for the hydrogen evolution reaction, oxygen evolution reaction, and oxygen reduction reaction. The catalyst is able to deliver a current density of 10 mA cm-2 in an alkaline electrolytic cell at a very low cell voltage of ∼1.60 V. When the catalyst is equipped in a liquid rechargeable Zn-air battery, it endowed a high open-circuit voltage with excellent cycling durability and outperformed the commercial Pt/C+IrO2 catalytic system. Furthermore, the Zn-air battery powered self-driven water splitting system is displayed using CrCo/CoN4@CNT-5 as sole trifunctional catalyst, delivering a high H2 evolution rate of 168 µmol h-1. Theoretical calculations reveal synergistic interaction between Co-N4 active sites and CrCo nanoparticles, favoring the Gibbs free energy for H2 evolution. The presence of Cr not only enhances the H2O adsorption and dissociation but also tunes the electronic property of CrCo nanoparticles to provide optimized hydrogen binding capacity to Co-N4 sites, thus giving rise to accelerated H2 evolution kinetics. This work highlights the importance of the presence of small quantity of Cr in enhancing the electrocatalytic activity as well as robustness of single-atom catalyst and suggests the design of the multifunctional robust electrocatalysts for long-term H2 evolution application.

A rare diagnosis of Langerhans cell histiocytosis made on thyroid histology with coexisting papillary thyroid cancer and AVP deficiency.

Summary: A 48-year-old Asian male, presented to the hospital for an elective total thyroidectomy in the context of 6.3 cm thyroid nodule. The fine needle aspiration cytology of the nodule confirmed papillary thyroid cancer (PTC) with some atypical histiocytes. He has a history of idiopathic arginine vasopressin deficiency (AVP-D) and has been taking oral DDAVP 100 µg daily, self-adjusting the dose based on thirst and polyuria. Additionally, he also has a history of recurrent spontaneous pneumothorax. His total thyroidectomy was aborted due to significant intraoperative bleeding, and his admission was further complicated by post-operative hyponatraemic seizure. Thyroid histology revealed the diagnosis of Langerhans cell histiocytosis (LCH), and further investigation with contrast CT demonstrated multi-organ involvement of the thyroid, lungs, and bones. Learning points: Langerhans cell histiocytosis (LCH) is a condition that can affect one or more organ systems, including the pituitary, where it can present as AVP deficiency. Strict monitoring of fluid balance, as well as serial monitoring of serum sodium, is essential in all patients with AVP-D in the perioperative setting. Iatrogenic hyponatraemic seizure is an uncommon but serious complication of DDAVP treatment in hospitalised patients with AVP-D. DDAVP dosing must be carefully monitored. LCH with multisystem involvement is an important mimic for metastatic conditions, and histological diagnosis is essential to guide treatment and prognosis. Although LCH without bone marrow involvement is unlikely to increase the risk of bleeding, its effect on tissue integrity may make surgery more challenging. BRAF-V600E mutation is an important driver mutation and a potential therapeutic target in the treatment of LCH.

Comparison of laparoscopic cholecystectomy in children at paediatric centres and adult centres: a systematic review and meta-analysis.

INTRODUCTION: Paediatric laparoscopic cholecystectomy (LC) is performed by both paediatric and adult surgeons. The aim of this review was to compare outcomes at paediatric centres (PCs) and adult centres (ACs). METHODS: A literature search was conducted, in accordance with PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines, for papers published between January 2000 and December 2020. Statistical analysis was performed using Stata® version 16 (StataCorp, College Station, TX, US). RESULTS: A total of 92 studies involving 74,852 paediatric LCs met the inclusion criteria. Over half (59%) of the LCs were performed at ACs. No significant differences were noted in the male-to-female ratio, mean age or mean body mass index between PCs and ACs. The main indications were cholelithiasis (34.1% vs 34.4% respectively, p=0.83) and biliary dyskinesia (17.0% vs 23.5% respectively, p<0.01). There was no significant difference in the median inpatient stay (2.52 vs 2.44 days respectively, p=0.89). Bile duct injury was a major complication (0.80% vs 0.37% respectively, p<0.01). Reoperation rates (2.37% vs 0.74% respectively, p<0.01) and conversion to open surgery (1.97% vs 4.74% respectively, p<0.01) were also significantly different. Meta-analysis showed no significant difference in overall complications (p=0.92). CONCLUSIONS: The number of LCs performed, intraoperative cholangiography use and conversion rates were higher at ACs whereas bile duct injury and reoperation rates were higher at PCs. Despite a higher incidence of bile duct injury at PCs, the incidence at both PCs and ACs was <1%. In complex cases, a joint operation by both paediatric and adult surgeons might be a better approach to further improve outcomes. Overall, LC was found to be a safe operation with comparable outcomes at PCs and ACs.

Landscaping tuberculosis multimorbidity: findings from a cross-sectional study in India.

BACKGROUND: Multimorbidity, the concurrent presence of two or more chronic conditions is an emerging public health challenge. Till date, most of the research have focused on the presence and interaction of selected co-morbidities in tuberculosis (TB). There exist a critical knowledge gap on the magnitude of multimorbidity among TB patients and its impact on health outcomes. METHODS: We undertook a cross-sectional study to assess the prevalence and patterns of multimorbidity among newly diagnosed TB patients in two states of India. A total of 323 patients were interviewed using a structured multimorbidity assessment questionnaire for primary care (MAQ-PC). MAQ-PC is already validated for Indian population and elicits 22 chronic conditions. We defined TB multimorbidity as the co-existence of TB with one or more chronic conditions and identified commonly occurring dyads (TB + single condition) and triads (TB + two conditions). RESULTS: More than half (52%) of TB patients reported multimorbidity. Among dyads, depression, diabetes mellitus (DM), acid peptic disease (APD), hypertension, chronic alcoholism, arthritis and chronic back ache (CBA) were the most common co-occurring conditions while 'DM + arthritis', 'depression + APD', 'depression + DM' were the most commonly occurring triads among TB patients. Factors such as increasing age, low levels of education, alcohol abusers, drug-resistant TB and having health insurance were significantly associated with multimorbidity among TB patients. CONCLUSIONS: Our findings suggest high prevalence of multimorbidity among newly diagnosed TB patients in India. The presence of concordant and discordant conditions with TB may increase the health complexity, thus necessitating appropriate care protocols. Given, the current situation, wherein TB and non-communicable diseases (NCD) services are delivered through collaborative framework between programmes, there is a need for addressing multimorbidity at the healthcare delivery level.

Temperature dependent structural properties of Mn1.90M0.10O3(M = Cr and Fe).

The polycrystalline samples of Mn1.90Cr0.10O3(MCO) and Mn1.90Fe0.10O3(MFO) have been investigated for their temperature dependent magnetic and structural properties. The Cr and Fe substitutions have significant effect on the magnetic and structural properties of Mn2O3. Like pristine Mn2O3, the Cr and Fe substituted samples MCO and MFO also exhibit two antiferromagnetic transitions; one at ∼77 K, ∼80 K, respectively and another at ∼40 K. Our room temperature synchrotron x-ray powder diffraction (SXRD) results confirm that both the MCO and MFO samples crystallize in cubic symmetry. The temperature dependent SXRD results demonstrate the cubic to orthorhombic structural transition for the studied samples. The pristine Mn2O3shows cubic to orthorhombic transition around 310 K, whereas this structural transition shifted towards lower temperature side with these substitutions i.e. around 240 K for MCO and 260 K for MFO. Interestingly, the centrosymmetricPcabto non-centrosymmetricPca21change in symmetry is also resolved at the ferroelectric ordering temperature for MCO.

Household drug-resistant TB contact tracing in Tajikistan.

BACKGROUND: Tajikistan has a high burden of rifampicin-resistant TB (RR-TB), with 2,700 new cases estimated for 2021 (28/100,000 population). TB is spread among household members through close interaction and children exposed through household contact progress to disease rapidly and frequently.METHODS: We retrospectively analysed programmatic data from household contact tracing in Dushanbe over 50 months. We calculated person-years of follow-up, contact tracing yield, number needed to screen (NNS) and number needed to test (NNT) to find one new case, and time to diagnosis.RESULTS: We screened 6,654 household contacts of 830 RR-TB index cases; 47 new RR-TB cases were detected, 43 in Year 1 and 4 in Years 2 or 3. Ten were aged <5 years; 46/47 had TB symptoms, 34/45 had chest radiographs consistent with TB, 11/35 were Xpert Ultra-positive, 29/32 were tuberculin skin test-positive and 28/47 had positive TB culture and phenotypic drug susceptibility results. The NNS to find one RR-TB case was 141.57 and the NNT was 34.49. The yields for different types of contacts were as follows: 0.7% for screened contacts, 2.9% for tested contacts, 17.0% for symptomatic contacts and 12.1% for symptomatic contacts aged below 5 years.CONCLUSION: RR-TB household contact tracing was feasible and productive in Tajikistan, a low middle-income country with an inefficient healthcare delivery system.

Dual Single-Atomic Co-Mn Sites in Metal-Organic-Framework-Derived N-Doped Nanoporous Carbon for Electrochemical Oxygen Reduction.

Synthesizing dual single-atom catalysts (DSACs) with atomically isolated metal pairs is a challenging task but can be an effective way to enhance the performance for electrochemical oxygen reduction reaction (ORR). Herein, well-defined DSACs of Co-Mn, stabilized in N-doped porous carbon polyhedra (named CoMn/NC), are synthesized using high-temperature pyrolysis of a Co/Mn-doped zeolitic imidazolate framework. The atomically isolated Co-Mn site in CoMn/NC is recognized by combining microscopic as well as spectroscopic techniques. CoMn/NC exhibited excellent ORR activities in alkaline (E1/2 = 0.89 V) as well as in acidic (E1/2 = 0.82 V) electrolytes with long-term durability and enhanced methanol tolerance. Density functional theory (DFT) suggests that the Co-Mn site is efficiently activating the O-O bond via bridging adsorption, decisive for the 4e- oxygen reduction process. Though the Co-Mn sites favor O2 activation via the dissociative ORR mechanism, stronger adsorption of the intermediates in the dissociative path degrades the overall ORR activity. Our DFT studies conclude that the ORR on an Co-Mn site mainly occurs via bridging side-on O2 adsorption following thermodynamically and kinetically favorable associative mechanistic pathways with a lower overpotential and activation barrier. CoMn/NC performed excellently as a cathode in a proton exchange membrane (PEM) fuel cell and rechargeable Zn-air battery with high peak power densities of 970 and 176 mW cm-2, respectively. This work provides the guidelines for the rational design and synthesis of nonprecious DSACs for enhancing the ORR activity as well as the robustness of DSACs and suggests a design of multifunctional robust electrocatalysts for energy storage and conversion devices.

Coupling Single-Ni-Atom with Ni-Co Alloy Nanoparticle for Synergistically Enhanced Oxygen Reduction Reaction.

Developing nonprecious metal-based oxygen reduction reaction (ORR) electrocatalysts with superior activity and durability is crucial for commercializing proton-exchange membrane (PEM) fuel cells. Herein, we report a metal-organic framework (MOF)-derived unique N-doped hollow carbon structure (NiCo/hNC), comprising of atomically dispersed single-Ni-atom (NiN4) and small NiCo alloy nanoparticles (NPs), for highly efficient and durable ORR catalysis in both alkaline and acidic electrolytes. Density functional theory (DFT) calculations reveal the strong coupling between NiN4 and NiCo NPs, favoring the direct 4e- transfer ORR process by lengthening the adsorbed O-O bond. Moreover, NiCo/hNC as a cathode electrode in PEM fuel cells delivered a stable performance. Our findings not only furnish the fundamental understanding of the structure-activity relationship but also shed light on designing advanced ORR catalysts.

Molecular surveillance detects high prevalence of the neglected parasite Mansonella ozzardi in the Colombian Amazon.

Mansonellosis is an undermapped insect-transmitted disease caused by filarial nematodes that are estimated to infect hundreds of millions of people globally. Despite their prevalence, there are many outstanding questions regarding the general biology and health impacts of the responsible parasites. Historical reports suggest that the Colombian Amazon is endemic for mansonellosis and may serve as an ideal location to pursue these questions in the backdrop of other endemic and emerging pathogens. We deployed molecular and classical diagnostic approaches to survey Mansonella prevalence among adults belonging to indigenous communities along the Amazon River and its tributaries near Leticia, Colombia. Deployment of a loop-mediated isothermal amplification (LAMP) assay on blood samples revealed an infection prevalence of ∼40% for Mansonella ozzardi . This assay identified significantly more infections than blood smear microscopy or LAMP assays performed using plasma, likely reflecting greater sensitivity and the ability to detect low microfilaremias or occult infections. Mansonella infection rates increased with age and were higher among males compared to females. Genomic analysis confirmed the presence of M. ozzardi that clusters closely with strains sequenced in neighboring countries. We successfully cryopreserved and revitalized M. ozzardi microfilariae, advancing the prospects of rearing infective larvae in controlled settings. These data suggest an underestimation of true mansonellosis prevalence, and we expect that these methods will help facilitate the study of mansonellosis in endemic and laboratory settings.

Primary bedaquiline resistance in Karakalpakstan, Uzbekistan.

BACKGROUND: Bedaquiline (BDQ) is widely used in the treatment of rifampicin-resistant TB (RR-TB). However, resistance to BDQ is now emerging. There are no standardised regimens for BDQ-resistant TB. This study aims to share experience in managing primary BDQ-resistant TB.METHODS: We performed a retrospective study of patients treated for RR-TB in Karakalpakstan, Uzbekistan, from January 2017 to March 2022. We identified patients with resistance to BDQ with no history of BDQ exposure. We describe baseline characteristics, treatment and follow-up of these patients.RESULTS: Twelve of the 1,930 patients (0.6%) had baseline samples resistant to BDQ with no history of BDQ exposure, 75% (9/12) of whom had been previously treated for TB. Ten (83.3%) were resistant to fluoroquinolones; respectively 66% and 50% had culture conversion by Month 3 and Month 6. The interim treatment outcomes were as follows: unfavourable treatment outcomes (3/12, 25%), favourable outcomes (2/12, 17%); the remaining seven (58%) were continuing treatment.CONCLUSIONS: A large proportion of the cases had previously been treated for TB and had TB resistant to quinolone. Both patients who had not experienced culture conversion by Month 3 had an unfavourable treatment outcome. Therefore, we recommend monthly monitoring of culture status for patients on treatment regimens for BDQ resistance.

Closed-loop recyclable and biodegradable thioester-based covalent adaptable networks.

Closed-loop recyclable and biodegradable aliphatic covalent adaptable networks (CANs) based on dynamic ß-CO thioester linkages that exhibit a service temperature beyond 100 °C are reported. These CANs possessing tensile strength and modulus values of up to 0.3 and 3 MPa, respectively, effectively undergo stress relaxation above 100 °C. The samples exhibit creep resistance ability and low hysteresis loss, and are repeatedly reprocessable at 120 °C. These CANs are depolymerizable to monomers under mild conditions and lose notable mechanical strength (92.4%) and weight (76.5%) within ∼35 days under natural biodegradation conditions.

Functionalized nanoparticles: Tailoring properties through surface energetics and coordination chemistry for advanced biomedical applications.

Significant advances in nanoparticle-related research have been made in the past decade, and amelioration of properties is considered of utmost importance for improving nanoparticle bioavailability, specificity, and catalytic performance. Nanoparticle properties can be tuned through in-synthesis and post-synthesis functionalization operations, with thermodynamic and kinetic parameters playing a crucial role. In spite of robust functionalization techniques based on surface chemistry, scalable technologies have not been explored well. The coordination enhancement via surface functionalization through organic/inorganic/biomolecules material has attracted much attention with morphology modification and shape tuning, which are indispensable aspects in the colloidal phase during biomedical applications. It is envisioned that surface amelioration influences the anchoring properties of nano interfaces for the immobilization of functional groups and biomolecules. In this work, various nanostructure and anchoring methodologies have been discussed, aiming to exploit their full potential in precision engineering applications. Simultaneous discussions on emerging characterization strategies for functionalized assemblies have been made to gain insights into functionalization chemistry. An overview of current advances and prospects of functionalized nanoparticles has been presented, with an emphasis on controllable attributes such as size, shape, morphology, functionality, surface features, Debye and Casimir interactions.