Student Satisfaction and Physical Health Effects of Online Learning Among Medical and Paramedical Undergraduates in Northern India: A Cross-Sectional Study.

BACKGROUND: Online modality of pedagogy was introduced in many medical institutes globally, especially during the COVID-19 pandemic. However, these techniques were not evaluated, either with respect to effectiveness or student satisfaction in terms of promoting successful educational outcomes. The current study was conducted to identify determinants of student satisfaction with respect to online learning, in the post-pandemic era. METHODS: A pilot-tested and validated online questionnaire was administered to 370 medical/paramedical students who attended online classes during the pandemic. The students were selected randomly from four different streams of a medical university, representing all the years of study. The questionnaire included Likert-type questions and was divided into two parts: socio-demographic profile and satisfaction with online learning. RESULTS: The response rate was 81.4%. Overall satisfaction with online learning among students was 35.9% and the areas of most satisfaction for students were user-friendliness of the online portal (65.5%), self-directed responsibilities assigned to pupils (49.9%), faculty accessibility/availability (48.8%) and timely evaluation, test and feedback (47.9%). The areas of most dissatisfaction were lack of personal effect as compared to offline learning (n=71, 23.6%), effect on social life (n=54, 17.9%), and feeling of not belonging to the online session (n=38, 12.6%). Multiple regression analysis demonstrated that having previous exposure to online courses and having a separate room led to more satisfaction, whereas the emergence of health problems led to poor satisfaction with the course. The duration of previous exposure to online courses was not a statistically significant predictor of satisfaction. One or more health problems were reported by 176 (58.5%) of the respondents. Some of the common health problems reported were eye strain (72.8%), headache (56.1%), insomnia (47.2%), stress (35.2%), muscle fatigue (22.6) and tingling sensation (10.6%). CONCLUSION: Adopting a combination of online and offline approaches, i.e., blended pedagogy, involving different methods to involve students and their feedback are important to ensure student satisfaction.

Diagnostic Stewardship in Clinical Microbiology: An Indispensable Component of Patient Care.

Emerging infectious diseases and increasing resistance to available antimicrobials are mapping the evolution of clinical microbiology and escalating the nature of undertakings required. Rapid diagnosis has become the need of the hour, which can affect diagnostic algorithms and therapeutic decisions simultaneously. Subsequently, the concept of 'diagnostic stewardship' was introduced into clinical practice for coherent implementation of available diagnostic modalities to ensure that these new rapid diagnostic technologies are conserved, rather than consumed as part of health care resources, with a view to improve the patient care and reduce Turnaround Time (TAT) and treatment expense. The present study highlights the requisite of diagnostic stewardship and outlines the infectious disease diagnostic modalities that can assist in its successful implementation. Diagnostic stewardship promotes precise, timely diagnostics, from the initial specimen collection and identification to reporting with appropriate TAT, so as to enable timely management of the patient. The main aim of diagnostic stewardship is to optimize the right choice of diagnostic test for the right patient to attain clinically significant reports with the least possible TAT for timely management and the least expected adverse effects for the patient, community, and the healthcare system. This underlines the requisite of a multifaceted approach to make technological advancements effective and successful for implementation as a part of diagnostic stewardship for the best patient care.

Logic "AND Gate Circuit" Based Mussel Inspired Polydopamine Nanocomposite as Bioactive Antioxidant for Management of Oxidative Stress and Neurogenesis in Traumatic Brain Injury.

In the intricate landscape of Traumatic Brain Injury (TBI), the management of TBI remains a challenging task due to the extremely complex pathophysiological conditions and excessive release of reactive oxygen species (ROS) at the injury site and the limited regenerative capacities of the central nervous system (CNS). Existing pharmaceutical interventions are limited in their ability to efficiently cross the blood-brain barrier (BBB) and expeditiously target areas of brain inflammation. In response to these challenges herein, we designed novel mussel inspired polydopamine (PDA)-coated mesoporous silica nanoparticles (PDA-AMSNs) with excellent antioxidative ability to deliver a new potential therapeutic GSK-3ß inhibitor lead small molecule abbreviated as Neuro Chemical Modulator (NCM) at the TBI site using a neuroprotective peptide hydrogel (PANAP). PDA-AMSNs loaded with NCM (i.e., PDA-AMSN-D) into the matrix of PANAP were injected into the damaged area in an in vivo cryogenic brain injury model (CBI). This approach is specifically built while keeping the logic AND gate circuit as the primary focus. Where NCM and PDA-AMSNs act as two input signals and neurological functional recovery as a single output. Therapeutically, PDA-AMSN-D significantly decreased infarct volume, enhanced neurogenesis, rejuvenated BBB senescence, and accelerated neurological function recovery in a CBI.

Insights into Changing Patterns of Extrapulmonary Tuberculosis in North India.

PURPOSE: Tuberculosis is one of the dreadful infections and India contributes to substantial burden of TB cases globally. Though majority of cases are pulmonary, extra-pulmonary tuberculosis (EPTB) share significant burden, more in HIV-positive persons. Despite the striking burden, very few studies have been conducted in India and present study was undertaken to determine trends of EPTB at our tertiary care centre. METHODS: This was a retrospective study conducted over a period of 4 years 3 months. Diagnosis of EPTB was based on suspected clinical features, with positive micobiological evidence with cartridge based nucleic acid amplification test (CBNAAT) with/without microscopy. RESULTS: A total of 10,560 samples (pulmonary and extra-pulmonary) were received during the study period, of which 3,972 were extrapulmonary. Of these, a total of 18% were noted to be positive for EPTB. Trend of positivity revealed highest burden in in 2018 and a decline was noted over the years, however, rise in cases was noted in 2022. Pleural, meningitis, musculoskeletal, peritoneal and pericardial TB was more common in males, while lymphadenitis was more common in females (p value: <0.0001). Pleural TB (31%) was the most common presentation, followed by lymphadenitis. A gradual decline in lymphadenitis was noted with significantly increasing trend only for musculoskeletal TB. Rifampicin resistance was detected in 7.45% of positive samples, of which the maximum rate of resistance was noted in lymph node aspirates (11.11%), followed by musculoskeletal and pleural samples. CONCLUSION: The present study showed a gradual decline in positivity of EPTB cases over the years. Younger productive age group with more propensity to transmit infection was the most commonly affected, with pleural TB as the most common presentation. Rare presentations of EPTB also contributed major share. Higher rates of resistance underline requisite to strengthen ongoing programs, to achieve the End TB strategy by 2025.

Variations in the Position of Mandibular Foramen in Temporomandibular Ankylosis Patients.

Aim: To evaluate the variation in the position of the mandibular foramen and mandibular canal in patients with and without temporomandibular joint ankylosis. Materials and Methods: 100 temporomandibular joints were evaluated of which 50 joints were ankylosed joints (Group A) and the rest 50 were normal joints (Group B) without ankylosis. These groups were further divided into those with growing potential (less than 18 years) and those without growing potential (above 18 years). The position of the mandibular foramen was measured from its center to the glenoid fossa, sigmoid notch, coronoid notch, gonion and posterior border on CBCT scans. The position of the mandibular canal was measured from the outer aspect of the canal to the lower border of the mandible, buccal and lingual cortical plates and the alveolus in the region of the 1st, 2nd and 3rd molars. Results: The mean distance of the foramen from the base of the skull in Group A was 19.01 mm while the same for Group B was 31.26 mm. The mandibular foramen was found to be closer to the occlusal plane (5.43 mm) in Group A as compared to the mean distance of 6.21 mm reported in Group B. There was no significant difference in the position of the foramen from the posterior border, gonion and sigmoid notch between the groups. The mental foramen was seen more commonly posterior to the 2nd premolar and closer to the first molar region in Group A while in Group B it was seen anterior or near the 2nd premolar. In Group A, the mean distance of the canal to the buccal cortical plate in the 1st and 2nd molar regions was 3.65 mm and 5.76 mm, respectively, while in Group B it was 6.09 mm and 6.59 mm. The canal was further away from the lower border in ankylosis cases (8.79 mm) than the control group (7.41 mm). On comparing the unaffected side in unilateral cases with the normal mandible, the canal and the foramen location were similar to that of a normal mandible with the values in the lower range that is usually seen in normal mandibles. Conclusion: Ankylosis of the mandible is a debilitating condition especially when it develops in an individual prior completion of growth as it can affect the mandibular anatomy. Understanding the variations that accompany a deranged mandible can assist the surgeon in planning of surgical procedures in a manner that limits the possible complications resulting from surgery.

Small-molecule inhibition of the METTL3/METTL14 complex suppresses neuroblastoma tumor growth and promotes differentiation.

The N6-methyladenosine (m6A) RNA modification is an important regulator of gene expression. m6A is deposited by a methyltransferase complex that includes methyltransferase-like 3 (METTL3) and methyltransferase-like 14 (METTL14). High levels of METTL3/METTL14 drive the growth of many types of adult cancer, and METTL3/METTL14 inhibitors are emerging as new anticancer agents. However, little is known about the m6A epitranscriptome or the role of the METTL3/METTL14 complex in neuroblastoma, a common pediatric cancer. Here, we show that METTL3 knockdown or pharmacologic inhibition with the small molecule STM2457 leads to reduced neuroblastoma cell proliferation and increased differentiation. These changes in neuroblastoma phenotype are associated with decreased m6A deposition on transcripts involved in nervous system development and neuronal differentiation, with increased stability of target mRNAs. In preclinical studies, STM2457 treatment suppresses the growth of neuroblastoma tumors in vivo. Together, these results support the potential of METTL3/METTL14 complex inhibition as a therapeutic strategy against neuroblastoma.

Prevalence of co-existent COVID-19-associated pulmonary aspergillosis (CAPA) and its impact on early mortality in patients with COVID-19-associated pulmonary mucormycosis (CAPM).

BACKGROUND: Data on mixed mould infection with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated pulmonary mucormycosis (CAPM) are sparse. OBJECTIVES: To ascertain the prevalence of co-existent CAPA in CAPM (mixed mould infection) and whether mixed mould infection is associated with early mortality (≤7 days of diagnosis). METHODS: We retrospectively analysed the data collected from 25 centres across India on COVID-19-associated mucormycosis. We included only CAPM and excluded subjects with disseminated or rhino-orbital mucormycosis. We defined co-existent CAPA if a respiratory specimen showed septate hyphae on smear, histopathology or culture grew Aspergillus spp. We also compare the demography, predisposing factors, severity of COVID-19, and management of CAPM patients with and without CAPA. Using a case-control design, we assess whether mixed mould infection (primary exposure) were associated with early mortality in CAPM. RESULTS: We included 105 patients with CAPM. The prevalence of mixed mould infection was 20% (21/105). Patients with mixed mould infection experienced early mortality (9/21 [42.9%] vs. 15/84 [17.9%]; p = 0.02) and poorer survival at 6 weeks (7/21 [33.3] vs. 46/77 [59.7%]; p = 0.03) than CAPM alone. On imaging, consolidation was more commonly encountered with mixed mould infections than CAPM. Co-existent CAPA (odds ratio [95% confidence interval], 19.1 [2.62-139.1]) was independently associated with early mortality in CAPM after adjusting for hypoxemia during COVID-19 and other factors. CONCLUSION: Coinfection of CAPA and CAPM was not uncommon in our CAPM patients and portends a worse prognosis. Prospective studies from different countries are required to know the impact of mixed mould infection.

Antibiotic Resistant Biofilms and the Quest for Novel Therapeutic Strategies.

Antimicrobial resistance (AMR) is one of the major leading causes of death around the globe. Present treatment pipelines are insufficient to overcome the critical situation. Prominent biofilm forming human pathogens which can thrive in infection sites using adaptive features results in biofilm persistence. Considering the present scenario, prudential investigations into the mechanisms of resistance target them to improve antibiotic efficacy is required. Regarding this, developing newer and effective treatment options using edge cutting technologies in medical research is the need of time. The reasons underlying the adaptive features in biofilm persistence have been centred on different metabolic and physiological aspects. The high tolerance levels against antibiotics direct researchers to search for novel bioactive molecules that can help combat the problem. In view of this, the present review outlines the focuses on an opportunity of different strategies which are in testing pipeline can thus be developed into products ready to use.

Ratiometric Fluorescent Probe Promotes Trans-differentiation of Human Mesenchymal Stem Cells to Neurons.

Development of multifunctional theranostics is challenging and crucial for deciphering complex biological phenomena and subsequently treating critical disease. In particular, development of theranostics for traumatic brain injury (TBI) and understanding its repair mechanism are challenging and highly complex areas of research. Recently, there have been interesting pieces of research work demonstrated that a small molecule-based neuroregenerative approach using stem cells has potential for future therapeutic lead development for TBI. However, these works demonstrated the application of a mixture of multiple molecules as a "chemical cocktail", which may have serious toxic effects in the differentiated cells. Therefore, development of a single-molecule-based potential differentiating agent for human mesenchymal stem cells (hMSCs) into functional neurons is vital for the upcoming neuro-regenerative therapeutics. This lead could be further extraploted for the design of theranostics for TBI. In this study, we have developed a multifunctional single-molecule-based fluorescent probe, which can image the transdifferentiated neurons as well as promote the differentiation process. We demonstrated a promising class of fluorescent probes (CP-4) that can be employed to convert hMSCs into neurons in the presence of fibroblast growth factor (FGF). This fluorescent probe was used in cellular imaging as its fluorescence intensity remained unaltered for up to 7 days of trans-differentiation. We envision that this imaging probe can have an important application in the study of neuropathological and neurodegenerative studies.

Salmonella Typhi: A Review of Antibiogram Journey in Developing Countries.

BACKGROUND: Typhoid fever poses a significant health challenge in low- and middleincome countries (LMiCs), impacting millions of individuals across various age groups. Its prevalence is particularly pronounced in South Asia. Factors contributing to its transmission in South Asia include rapid unplanned urbanization, urban-rural disparities, provision of poor water and sanitation facilities, and open defecation. The mortality rate of typhoid fever is up to 1%, and those who survive have a protracted period of poor health and carry an enormous financial burden. The treatment is further complicated by the emerging antibiotic resistance leaving few treatment options in hands. This issue has become more urgent due to the further emergence of extended drug-resistant (XDR) and multidrugresistant (MDR) typhoid strains, as well as their subsequent global spread. Fluoroquinoloneresistant Salmonella spp. is currently classified by the World Health Organization (WHO) as a high (Priority 2) pathogen. As a result, establishing minimum inhibitory concentrations (MIC) according to the latest guidelines may prove effective in treating typhoid fever and minimizing the rising threat of drug resistance.

Increased electrode impedance as an indicator for early detection of deep brain stimulation (DBS) hardware Infection: Clinical experience and in vitro study.

BACKGROUND: When deep brain stimulation (DBS) infections are identified, they are often too advanced to treat without complete hardware removal. New objective markers to promptly identify DBS infections are needed. We present a patient with GPi (globus pallidus interna) DBS for dystonia, where the electrode impedance unexpectedly increased 3-months post-operatively, followed by serologic and hematologic markers of inflammation at 6-months, prompting explantation surgery. We recreated these conditions in a laboratory environment to analyze the pattern of changing of electrical impedance across the contacts of a DBS lead following Staphylococcus biofilm formation. METHODS: A stainless-steel culture chamber containing 1 % brain heart infusion agar was used. A DBS electrode was dipped in peptone water containing a strain of S. aureus and subsequently introduced into the chamber. The apparatus was incubated at 37 °C for 6 days. Impedance was measured at 24hr intervals. A control experiment without S. Aureus inoculation was used to determine changes in impedance over a period of 6-days. RESULTS: The mean monopolar impedance on day-1 was 751.8 ± 23.8 Ω and on day-3 was 1004.8 ± 68.7 Ω, a 33.7 % rise (p = 0.007). A faint biofilm formation could be seen around the DBS lead by day-2 and florid growth by day-3. After addition of the linezolid solution, a 15.9 % decrease in monopolar impedance was observed from day 3-6 (p = 0.003). CONCLUSION: This study gives insight into impedance trends following a hardware infection in DBS. Increased impedance outside expected norms may be valuable for early prediction of infection. Furthermore, timely management using antibiotics might reduce the frequency of infection-related explant surgeries.

Emergence of Monkeypox (MPX): A Close Relative of Small Pox During COVID-19 Era.

After the eradication of smallpox (SPX), a new zoonotic threat that can trigger outbreaks has emerged. It may be fatal during the COVID19 outbreak. Humanity continues to be threatened due to re-emergence of the outbreaks. In most cases, new emerging viral agents originate from nonhuman hosts with zoonotic origins. Recent outbreaks of zoonotic infectious diseases with the potential to cause epidemics and pandemics continue to pose a major threat to the health security of entire regions, continents, and the world at large. Around five decades backthat Monkeypox (MPX) was reported for the first time in the Democratic Republic of the Congo (DRC) and was then confined to Central Africa only. Over the time, it has spread to other regions of Africa as well as outside Africa. As of August 2022, 40398 infections have been confirmed in almost 68 countries that have never reported MPX before. The majority of infections have been reported in Europe and Southeast Asia. On 23rd August 2022, MPX was declared a public health emergency of international concern, a step below declaring any disease as a pandemic. The article discusses the recent history of MPX outbreaks, as well as the evolving clinical manifestations of the disease, and the possible causes of the increase in cases, including the cessation of SPX vaccinations.

Risk factors, mortality, and predictors of survival in COVID-19-associated pulmonary mucormycosis: a multicentre retrospective study from India.

OBJECTIVES: To compare COVID-19-associated pulmonary mucormycosis (CAPM) with COVID-19-associated rhino-orbital mucormycosis (CAROM), ascertain factors associated with CAPM among patients with COVID-19, and identify factors associated with 12-week mortality in CAPM. METHODS: We performed a retrospective multicentre cohort study. All study participants had COVID-19. We enrolled CAPM, CAROM, and COVID-19 subjects without mucormycosis (controls; age-matched). We collected information on demography, predisposing factors, and details of COVID-19 illness. Univariable analysis was used to compare CAPM and CAROM. We used multivariable logistic regression to evaluate factors associated with CAPM (with hypoxemia during COVID-19 as the primary exposure) and at 12-week mortality. RESULTS: We included 1724 cases (CAPM [n = 122], CAROM [n = 1602]) and 3911 controls. Male sex, renal transplantation, multimorbidity, neutrophil-lymphocyte ratio, intensive care admission, and cumulative glucocorticoid dose for COVID-19 were significantly higher in CAPM than in CAROM. On multivariable analysis, COVID-19-related hypoxemia (aOR, 2.384; 95% CI, 1.209-4.700), male sex, rural residence, diabetes mellitus, serum C-reactive protein, glucocorticoid, and zinc use during COVID-19 were independently associated with CAPM. CAPM reported a higher 12-week mortality than CAROM (56 of the 107 [52.3%] vs. 413 of the 1356 [30.5%]; p = 0.0001). Hypoxemia during COVID-19 (aOR [95% CI], 3.70 [1.34-10.25]) and Aspergillus co-infection (aOR [95% CI], 5.40 [1.23-23.64]) were independently associated with mortality in CAPM, whereas surgery was associated with better survival. DISCUSSION: CAPM is a distinct entity with a higher mortality than CAROM. Hypoxemia during COVID-19 illness is associated with CAPM. COVID-19 hypoxemia and Aspergillus co-infection were associated with higher mortality in CAPM.

Risk factor and resistance profile of colistin resistant Acinetobacter baumannii and Klebsiellapneumoniae.

PURPOSE: Antimicrobial resistance is one of the major global health concerns, which is relentless despite multipronged measures. Carbapenems and colistin, drug of choice for multi drug resistant Klebsiella pneumoniae and Acinetobacter species, have also been rendered of less use. This underlines the need to decipher prevalence of colistin resistance comprehensively for formulation of hospital and country-wise antibiogram. We conducted this study to decipher the prevalence of colistin resistance in our tertiary care centre of North India. MATERIALS AND METHODS: This was a prospective, case control study conducted over a period of one and half years. All carbapenem resistant Klebsiella pneumoniae and Acinetobacter isolates were included. Kirby-Bauer method of disc diffusion was used for all antibiotics, except colistin for which broth microdilution was performed and interpreted using CLSI guidelines. Demographic details, risk factors and outcome details were recorded. Genotypic characterization was performed using representative strains, for blaNDM, blaKPC and blaOXA-48. RESULTS: Of 103 carbapenem resistant isolates, 7 were found to be colistin resistant. Median age was 43 years, with male:female ratio of 1.1:1. 35% isolates were from pus samples, followed by endotracheal aspirate. Colistin resistance was more in ICUs than wards. Presence of indwelling devices was noted as the most common risk factor, followed by previous antibiotic exposure and use of steroids/immunosuppressants. Indwelling devices, steroids/immunosuppressants usage, length of hospital stay, COPD, prior usage of carbapenems, piperacillin-tazobactam and colistin, usage of ampicillin-sulbactam during hospital stay, were statistically significant. Mortality was noted in 4 cases, with statistical difference between control and case arm. The blaNDM and blaOXA-48 were noted in 3 and 2 isolates respectively, with absence of blaKPC. CONCLUSION: The present study unravels incidence, risk factors and resistance encoding genes at our centre. This is of immense help in formulation of antibiotic policies and guidance for infection control measures.

Effectiveness of prophylactic oral and/or vaginal probiotic supplementation in the prevention of recurrent urinary tract infections: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Widespread antibiotic resistance has sparked interest in the lookout for non-antibiotic strategies, particularly focusing on probiotics for the prevention of recurrent urinary tract infections (UTIs). We evaluated the effectiveness of prophylactic probiotic supplementation through oral and intravaginal routes in the prevention of recurrent UTIs. METHODS: This double-blind, placebo-controlled study enrolled 174 premenopausal women with a history of recurrent UTIs and randomized them to either of the four treatment groups, namely, Placebo (G1, oral placebo+vaginal placebo); Oral probiotic (G2, oral lactic acid bacteria and bifidobacteria+vaginal placebo); Vaginal probiotic (G3, oral placebo+vaginal lactobacilli); and Probiotic combination (oral lactic acid bacteria and bifidobacteria+vaginal lactobacilli), for 4 months. Participants were followed-up for symptomatic UTIs for one year. The primary endpoints were the number of symptomatic UTIs at 4 months, the proportion of subjects with at least one symptomatic UTI, and the time to the first symptomatic UTI. RESULTS: The incidence of UTI at 4 months in G1, G2, G3 and G4 was 70.4%, 61.3%, 40.9%, and 31.8%, respectively. The mean number of symptomatic UTI recurrence at 4 months was significantly lower (p<0.05) in G3 (1.06) and G4 (1.07) compared to G1 (2.1) and G2 (1.63). Further, the time to first symptomatic UTI (days) was significantly longer (p<0.05) in G3 (123.8) and G4 (141.8) compared to G1 (69.3) and G2 (71.9). Probiotic supplementations were well tolerated with no serious adverse events. CONCLUSION: Prophylactic supplementation with either vaginal probiotics or in combination with oral probiotics demonstrated effectiveness in preventing recurrent symptomatic UTI episodes.

The new Xpert Mycobacterium tuberculosis/rifampicin (MTB/Rif) Ultra assay in comparison to Xpert MTB/Rif assay for diagnosis of tuberculosis in children and adolescents.

BACKGROUND: Microbiological diagnosis of pediatric tuberculosis (TB) using conventional microbiological techniques has been challenging due to paucibacillary nature of the disease. Molecular methods using cartridge-based tests like Xpert, have immensely improved diagnosis. A novel next-generation cartridge test, Xpert Ultra, incorporates two additional molecular targets and claims to have much lower detection limit. We attempted to compare the two techniques in presumptive pediatric TB patients. OBJECTIVES: The aim of this study was to compare the diagnostic performance of Xpert MTB/Rif Ultra with Xpert MTB/Rif for the detection of pediatric TB. STUDY DESIGN: This is an observational comparative analytical study. METHODS: Children under 15 years of age with presumptive TB were enrolled. Appropriate specimens were obtained (sputum, induced sputum or gastric aspirate for suspected pulmonary TB, cerebrospinal fluid for suspected tubercular meningitis and pleural fluid for suspected tubercular pleural effusion), subjected to smear microscopy, mycobacterial culture, Xpert and Xpert ultra tests and other appropriate diagnostic investigations. RESULTS: Out of 130 enrolled patients, 70 were diagnosed with TB using a composite reference standard (CRS). The overall sensitivity of Xpert was 64.29% [95% confidence interval (CI) 51.93-75.93%] and that of Xpert Ultra was 80% (95% CI 68.73-88.61%) with 100% overall specificity for both. The sensitivity of Xpert and Xpert Ultra in pulmonary specimens (n = 112) was 66.67% and 79.37% and in extrapulmonary specimens (n = 18) was 42.86% and 85.71%, respectively. CONCLUSION: Our study found Ultra to be more sensitive than Xpert for the detection of Mycobacterium tuberculosis in children. Our findings support the use of Xpert Ultra as initial rapid molecular diagnostic test in children under evaluation for TB.

Unsupervised machine learning to investigate trajectory patterns of COVID-19 symptoms and physical activity measured via the MyHeart Counts App and smart devices.

Previous studies have associated COVID-19 symptoms severity with levels of physical activity. We therefore investigated longitudinal trajectories of COVID-19 symptoms in a cohort of healthcare workers (HCWs) with non-hospitalised COVID-19 and their real-world physical activity. 121 HCWs with a history of COVID-19 infection who had symptoms monitored through at least two research clinic visits, and via smartphone were examined. HCWs with a compatible smartphone were provided with an Apple Watch Series 4 and were asked to install the MyHeart Counts Study App to collect COVID-19 symptom data and multiple physical activity parameters. Unsupervised classification analysis of symptoms identified two trajectory patterns of long and short symptom duration. The prevalence for longitudinal persistence of any COVID-19 symptom was 36% with fatigue and loss of smell being the two most prevalent individual symptom trajectories (24.8% and 21.5%, respectively). 8 physical activity features obtained via the MyHeart Counts App identified two groups of trajectories for high and low activity. Of these 8 parameters only 'distance moved walking or running' was associated with COVID-19 symptom trajectories. We report a high prevalence of long-term symptoms of COVID-19 in a non-hospitalised cohort of HCWs, a method to identify physical activity trends, and investigate their association. These data highlight the importance of tracking symptoms from onset to recovery even in non-hospitalised COVID-19 individuals. The increasing ease in collecting real-world physical activity data non-invasively from wearable devices provides opportunity to investigate the association of physical activity to symptoms of COVID-19 and other cardio-respiratory diseases.

Triple Burden: The Incorrigible Threat of Tuberculosis, HIV, and COVID-19.

The Coronavirus-19 (COVID-19) hasn't seen the dawn since its emergence, however waxing and waning has resulted in the emergence of deadly variants. The effects of the pandemic have not been limited to its virulence, but have rather conferred multiple collateral effects, especially in developing countries; thereby, designating it as a SYNDEMIC. The same culminated in neglect of non-COVID-19 conditions like tuberculosis (TB) and human immunodeficiency virus-acquired immunodeficiency syndrome (HIV/AIDS). Besides being the prognostic factor for severe COVID-19, these infections in hidden pockets served as a reservoir for the emergence of the deadly Omicron. Another significant impact of this juxtaposition was on the delivery of healthcare services for TB and HIV. The unanticipated COVID-19 pandemic turned the path of ongoing progress of elimination programs. Direct consequences of the COVID-19 pandemic were pronounced on diagnosis, treatment, and services for patients with TB and HIV. Essential TB services were reallocated to the COVID-19 rapid response task force. However, despite escalating the tribulations, this triple burden has simultaneously taught lessons to escalate the progress of halted programs. The pandemic has catalyzed an unusual level of collaboration among scientists, which can be exploited for TB and HIV. Fast-track diagnostics, digitalization, contact tracing, and vaccine development have enabled the world to envision the same for TB/HIV.

Dual immunization with CdtB protein and flagellin epitope offers augmented protection against enteric fever in mice.

AIMS: Present study has explored the protective response of dual immunization using two different antigenic entities (i.e. flagellin epitope and cytolethal distending toxin subunit B (CdtB) protein) against lethal challenge of typhoidal serovars in a murine model. MAIN METHODS: In-vitro immunogenicity of flagellin epitope-BSA conjugate and CdtB protein was confirmed using Indirect ELISA of typhoid positive patients' sera. Further, both entities were administered intraperitoneally in mice individually or in combination, followed by lethal challenge of typhoidal Salmonellae. Various parameters were analysed such as bacterial burden, mice survival, histopathological analysis, cytokine analysis and immunophenotyping. Serum samples obtained from the immunized mice were used for passive immunization studies, wherein mice survival and mechanism of action of the generated antibodies was studied. KEY FINDINGS: Active immunization studies using the combination of both entities demonstrated improved mice survival after lethal challenge with typhoidal Salmonellae, reduced bacterial burden in organs, expression of immunophenotypic markers in splenocytes and restored tissue histoarchitecture. When used in combination, the effective doses of both the candidates reduced which may be attributed to multiprong approach used by the immune system to recognize Salmonella. Passive immunization studies further determined the protective efficacy of generated antibodies by different mechanisms such as complement mediated bactericidal action, swarming inhibition and increased phagocytic uptake. SIGNIFICANCE: Present study is the first phase of the proof-of-concept which may prove to be beneficial in developing an effective bi-functional vaccine candidate to render protection against both Vi-positive as well as Vi-negative Salmonella strains.