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Ubiquitination typically involves covalent linking of ubiquitin (Ub) to a lysine residue on a protein substrate. Recently, new facets of this process have emerged, including Ub modification of non-proteinaceous substrates like ADP-ribose by the DELTEX E3 ligase family. Here, we show that the DELTEX family member DTX3L expands this non-proteinaceous substrate repertoire to include single-stranded DNA and RNA. Although the N-terminal region of DTX3L contains single-stranded nucleic acid binding domains and motifs, the minimal catalytically competent fragment comprises the C-terminal RING and DTC domains (RD). DTX3L-RD catalyses ubiquitination of the 3’-end of single-stranded DNA and RNA, as well as double-stranded DNA with a 3’ overhang of two or more nucleotides. This modification is reversibly cleaved by deubiquitinases. NMR and biochemical analyses reveal that the DTC domain binds single-stranded DNA and facilitates the catalysis of Ub transfer from RING-bound E2-conjugated Ub. Our study unveils the direct ubiquitination of nucleic acids by DTX3L, laying the groundwork for understanding its functional implications.

Burn camps play a vital role in the recovery of burn survivors by allowing them to develop the confidence and skill sets needed to reintegrate back into society. During the COVID-19 pandemic, burn camps across the United States and Canada could not hold any in-person activities. They had to either pause burn camps or quickly adapt to a virtual online platform. A 37-item electronic survey was developed and emailed to burn camp directors in the United States and Canada to determine what adaptations were necessary during the pandemic. This survey allowed directors to provide details on many facets such as camp format, successes observed, and challenges encountered. Twenty-one of 34 (62%) burn camp organizations completed the survey. Thirteen of the 21 (62%) respondents held virtual burn camps in 2020 while everyone else canceled their camps in 2020. The mean number of camps offered per organization decreased from 6.3 in 2019 to 4.7 in 2020. The average number of burn survivors and family members participating also dropped in that same period (2019 aggregate mean = 229.2 vs 2020 aggregate mean = 151.4). Components of virtual camp included video conferencing platforms, "camp-in-a-box" activities, and some prerecorded sessions. Most camp directors believed that their campers were satisfied with the virtual format. Factors allowing for a successful virtual camp included an effective online platform, scheduling adequate duration of programs, and appropriate staffing levels. Most common barriers to an effective virtual camp were participant engagement, special needs/accessibility concerns, and staff effectiveness in this format. While challenging, burn camps can be held in a virtual format successfully with proper planning, staff training, and support of campers and their families.

Background: India became the first country in the WHO South-East Asia Region (SEAR) to introduce the rotavirus vaccine (RVV) in the Universal immunization programme (UIP) in 2016 with nationwide expansion by 2019. It was a landmark move to reduce the diarrheal disease burden in under-five children. To assess the implementation process of introduction of RVV, Post Introduction Evaluation (PIE) was conducted in March 2022. Methods: The evaluation was conducted across 14 states, 28 districts and 28 health facilities to obtain a nationwide geographical inclusion. Stakeholders involved in program decision-making, planning, training, vaccine delivery, logistics, and communication from all levels (National, state, district, health facility, health worker, caregiver) were interviewed using standardized data collection tool for PIE (adapted from the standard WHO PIE questionnaire) and scripted on a digital tool. Results: A total of 260 interviews were conducted. Political willingness, well-planned preparedness activities, securing vaccines timely, strong supply chain monitoring, availability of domestic RVV products, quality trainings and intense communication activities were the key factors identified for the successful RVV introduction. Key activities during the introduction included cold chain space assessment, trainings of healthcare workforce, dissemination of job aids, updation of recording & reporting formats and strengthening of AEFI surveillance. Lack of community awareness for immunization in a few areas, fear of AEFI amongst some caregivers and local issues with Alternate Vaccine Delivery (AVD) were some reported challenges in achieving high coverage for RVV. Conclusions: Overall, the nationwide roll-out of RVV was smooth and the vaccine has been well-accepted in the community. The assessment emphasizes on having a well-strategized operational and communication planning, which is very crucial for any new vaccine introduction.

Background and aims: The Rotavirus vaccine (RVV) introduction is a landmark event in the history of Indian public health as for the first time a novel, low-cost indigenous vaccine was introduced in a short timeline between 2016 and 2019. As per WHO mandate, post-introduction evaluation (PIE) be conducted within 6 to 12 months of vaccine introduction to provide an understanding of the operational aspects of the program. For RVV PIE, an innovative approach to developing and deploying a digitized tool was employed. The present study aims to document the processes followed for digitizing the data collection and analysis tools. Methods: The development of the RVV-PIE digital tool was undertaken in two phases. In the first phase, conceptualization and iteration of the modified WHO PIE tool were undertaken. Questions were organized sequentially to ensure natural progression in responses. The finalized questionnaire was converted to a digital version and extensive dummy data was entered to improve automated qualitative data analysis. Phase 2 involved updating the draft tool and incorporating changes to provide a field-tested version for deployment. Results: The digital version of the tool was successfully developed. The GPS functionality of the tool allowed live tracking of data collection making the process more accountable. The tool was prepopulated with reference materials and data points for easy reference and retrieval by the evaluators. The digitization of the tool also allowed easy visualization of data through maps, charts, and graphs on a real-time user-friendly dashboard. Conclusions: The digitization of the PIE tool for RVV in India has been a great learning experience where the dire situation of an ongoing pandemic catapulted us towards a more efficient and comprehensive process innovation. The RVV PIE tool could serve as a customizable digital PIE tool for other health programs heralding an era of a more effective and proficient process of PIE.

Background With the expanding eligibility for endovascular therapy (EVT) of patients presenting in the late window (6–24 hours after last known well), we aimed to derive a score to predict favorable outcomes associated with EVT versus best medical management. Methods and Results A multinational observational cohort of patients from the CLEAR (Computed Tomography for Late Endovascular Reperfusion) study with proximal intracranial occlusion (2014–2022) was queried (n=58 sites). Logistic regression analyses were used to derive a 9‐point score for predicting good functional outcome (modified Rankin Scale score 0–2 or return to premorbid modified Rankin Scale score) at 90 days, with sensitivity analyses for prespecified subgroups conducted using bootstrapped random forest regressions. Secondary outcomes included 90‐day functional independence (modified Rankin Scale score 0–2), poor outcome (modified Rankin Scale score 5–6), and 90‐day survival. The score was externally validated with a single‐center cohort (2014–2023). Of the 3231 included patients (n=2499 EVT), a 9‐point score included age, early computed tomography ischemic changes, and stroke severity, with higher points indicating a higher probability of a good functional outcome. The areas under the curve for the primary outcome among EVT and best medical management subgroups were 0.72 (95% CI, 0.70–0.74) and 0.87 (95% CI, 0.84–0.90), respectively, with similar performance in the external validation cohort (area under the curve, 0.71 [95% CI, 0.66–0.76]). There was a significant interaction between the score and EVT for good functional outcome, functional independence, and poor outcome (all Pinteraction

Background: Estimates suggest that 78,000 children died due to rotavirus gastroenteritis annually between 2011 and 2013 in India. The north eastern state of Assam reported 38.4% pediatric diarrheal admissions testing positive for rotavirus. Rotavirus vaccine (RVV) was introduced in Assam in 2017 following which the National Family Health Survey-5 (NFHS-5) (2019) revealed low RVV coverage in Assam with wide variation between the districts. the current study was conceptualized and undertaken to capture the enablers and barriers to RVV coverage in Assam. Methods: Qualitative study conducted in 5 randomly selected districts in Assam. Participants (key informants) were recruited by purposive sampling at each level of the health system including healthcare officials, service providers and caregivers based on availability. Thirty-five in-depth interviews (IDIs) and five focus group discussions (FGDs) were conducted. Interviews were tape recorded and transcribed. Data was coded and analyzed using the thematic framework approach. Results: Findings from the qualitative data collection were collated and analyzed under 7 identified themes. Difficult terrain, limited service provider availability and no catch-up training for new recruits were some of the barriers to RVV coverage. In contrast, Information, Education & Communication (IEC) in vernacular language, RVV safety profile, development partner support and adequate RVV supply were identified as some of the enablers of RVV coverage. Conclusion: Few broad recommendations to overcome identified barriers include comprehensive inter-sectoral coordination, regular monitoring and frequent refresher training sessions. There is a need for a future study utilizing existing coverage data and larger sample size to triangulate the findings of this study.

Background: Despite an increasing incidence of Staphylococcus aureus infection and dissemination in Pakistan, the epidemiology of different Staphylococcus aureus research clones has been the subject of only a small number of investigations. By analyzing the collected data sequence, this study was designed to study the epidemiology of Staphylococcus aureus in the area using multilocus sequence typing (MLST). Methods: A total of 1015 staphylococcus strains collected from the city's tertiary care facilities were biochemically screened, followed by antimicrobial susceptibility testing against a panel of 13 antibiotics. Analyzed methicillin-resistant Staphylococcus aureus (MRSA) was subjected to molecular characterization using multilocus sequence typing (MLST), clonal complex analysis, recombination testing, and phylogenetic analysis. Results: Approximately 421 bacteria were verified as Staphylococcus aureus by biochemical analysis. 57% of the isolates exhibited multidrug resistance, of which 89% were found to be methicillin-resistant Staphylococcus aureus (MRSA). MLST results in a total of 39 sequence types (ST) and 5 clonal complexes (CC), out of which twenty-two STs were newly documented worldwide. The most common CC identified was CC8. The direct sequencing data also revealed significant shifts at MLST loci, with point mutations resulting in the aroE-343 and tpi-278 alleles. Conclusions: This study concludes that there is high diversity in the locally circulating clones of Staphylococcus aureus present in nature and that they are defined by their geographic epidemiology. These findings have practical implications for public health, including the need for tailored infection control strategies, antibiotic stewardship, global surveillance, and a deeper understanding of bacterial evolution.

Background and Purpose Effect of endovascular therapy (EVT) in acute large vessel occlusion (LVO) patients with tandem lesions (TLs) within 6–24 hours after last known well (LKW) remains unclear. We evaluated the clinical and safety outcomes among TL-LVO patients treated within 6–24 hours. Methods This multicenter cohort was divided into two groups, based on LKW to puncture time: early window (

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Objective:. We investigated frailty’s impact on traumatic subdural hematoma (tSDH), examining its relationship with major complications, length of hospital stay (LOS), mortality, high level of care discharges, and survival probabilities following nonoperative and operative management. Background:. Despite its frequency as a neurosurgical emergency, frailty’s impact on tSDH remains underexplored. Frailty characterized by multisystem impairments significantly predicts poor outcomes, necessitating further investigation. Methods:. A retrospective study examining tSDH patients ≥18 years and assigned an abbreviated injury scale score ≥3, and entered into ACS-TQIP between 2007 and 2020. We employed multivariable analyses for risk-adjusted associations of frailty and our outcomes, and Kaplan-Meier plots for survival probability. Results:. Overall, 381,754 tSDH patients were identified by mFI-5 as robust—39.8%, normal—32.5%, frail—20.5%, and very frail—7.2%. There were 340,096 nonoperative and 41,658 operative patients. The median age was 70.0 (54.0–81.0) nonoperative, and 71.0 (57.0–80.0) operative cohorts. Cohorts were predominately male and White. Multivariable analyses showed a stepwise relationship with all outcomes P

India had decided to roll out PCV in India in 2015, but successful implementation of any new vaccine introduction mandates an enormous effort. PCV was scaled up during the COVID-19 pandemic, which posed new, unprecedented challenges in the vaccine rollout. However, India successfully expanded PCV in the country in record time across all states and Union Territories.During the pandemic, supply-side restrictions, delayed vaccine shipments, staff shortages, and restrictions in conducting training negatively affected the roll-out of PCV across the country. However, despite the ongoing pandemic, India successfully rolled out PCV across the country in 7 months. In this review, the authors have conducted a narrative review to delineate the crucial factors that helped in the successful expansion of PCV.

Background: Pneumonia is one of the leading causes of death in under-5 children in India. This led the Ministry of Health & Family Welfare (MoHFW) in India to decide for the nationwide roll-out of the Pneumococcal Conjugate Vaccine (PCV). However, the introduction of PCV became more complex in the face of unprecedented challenges set forth by the COVID-19 pandemic. The study aims to assess enablers and barriers to the introduction of PCV in India during the pandemic. Methodology: Qualitative research approach involving key-informant interviews from John Snow India (JSI), the lead technical agency that supported MoHFW in the PCV expansion was employed to delineate the enablers and barriers. Principle of saturation was employed to derive the sample size. Thematic analysis using inductive approach was based on the modified World Health Organization (WHO) framework for new vaccine introduction impact on the Immunization and Health Systems, using NVIVO 12 qualitative data analysis software. Results: A total of 11 key informants (4 national-level program managers and 7 state technical officers) were telephonically interviewed. The study found social acceptance, lower cost of the vaccine, and intensive communication activities as potential enablers. Other enablers for PCV introduction included a robust vaccine supply-chain system, ample cold-chain space availability, and strong political commitment, despite the ongoing second wave. Further, the identified barriers included poor physical access, insufficient social mobilization, and limited advocacy along with a stretched workforce. Conclusion: The study delineated several enablers and barriers to introducing PCV in the country during the pandemic. The existing barriers in the PCV roll-out prompted the need to address these gaps, making key program-based recommendations to improve future new vaccine introductions during the pandemic.

The doping of engineered nanomaterials (ENMs) is a key tool for manipulating the properties of ENMs (e.g., electromagnetic, optical, etc.) for different therapeutic applications. However, adverse health outcomes and the cellular biointeraction of doped ENMs, compared to undoped counterparts, are not fully understood. Previously, we have shown that doping manganese oxide nanoparticles with ZnO (ZnO-MnO2 NPs) improved their catalytic properties. In this study, we assessed the toxicity of ZnO-MnO2 NPs in Raw 264.7 cells. NPs were prepared via an eco-friendly, co-precipitation method and characterized by several techniques, including transmission and scanning electron microscopy, X-ray diffraction, and Fourier transform infrared. The physicochemical properties of ZnO-MnO2 NPs, including size, morphology, and crystalline structure, were almost identical to MnO2 NPs. However, ZnO-MnO2 NPs showed slightly larger particle aggregates and negative charge in cell culture media. Exposure to ZnO-MnO2 NPs resulted in lower toxicity based on the cell viability and functional assay (phagocytosis) data. Exposure to both NPs resulted in the activation of the cell inflammatory response and the generation of reactive oxygen species (ROS). Despite this, exposure to ZnO-MnO2 NPs was associated with a lower toxicity profile, and it resulted in a higher ROS burst and the activation of the cell antioxidant system, hence indicating that MnO2 NP-induced toxicity is potentially mediated via other ROS-independent pathways. Furthermore, the cellular internalization of ZnO-MnO2 NPs was lower compared to MnO2 NPs, and this could explain the lower extent of toxicity of ZnO-MnO2 NPs and suggests Zn-driven ROS generation. Together, the findings of this report suggest that ZnO (1%) doping impacts cellular biointeraction and the consequent toxicological outcomes of MnO2 NPs in Raw 264.7 cells.