Accurately Modeling RNA Stem-Loops in an Implicit Solvent Environment.

Ribonucleic acid (RNA) molecules can adopt a variety of secondary and tertiary structures in solution, with stem-loops being one of the more common motifs. Here, we present a systematic analysis of 15 RNA stem-loop sequences simulated with molecular dynamics simulations in an implicit solvent environment. Analysis of RNA cluster ensembles showed that the stem-loop structures can generally adopt the A-form RNA in the stem region. Loop structures are more sensitive, and experimental structures could only be reproduced with modification of CH···O interactions in the force field, combined with an implicit solvent nonpolar correction to better model base stacking interactions. Accurately modeling RNA with current atomistic physics-based models remains challenging, but the RNA systems studied herein may provide a useful benchmark set for testing other RNA modeling methods in the future.

Patient outcomes after implementation of transitional care protocols in elective neurosurgery: a systematic review and meta-analysis.

OBJECTIVE: 30-day readmissions are a significant burden on the healthcare system. Postoperative transitional care protocols (TCPs) for safe and efficient discharge planning are being more widely adopted to reduce readmission rates. Currently, little evidence exists to justify the utility of TCPs for improving patient outcomes in elective neurosurgery. The objective of this systematic review was to determine the extent to which TCPs reduce adverse outcomes in patients undergoing elective neurosurgical procedures. MATERIALS AND METHODS: A systematic review and meta-analysis was conducted after PROSPERO registration. Pubmed, Embase, and Cochrane review databases were searched through February 1, 2024. Keywords included: "transitional care AND neurosurgery", "Discharge planning AND neurosurgery". Articles were included if they assessed postoperative TCPs in an adult population undergoing elective neurosurgeries. Exclusion criteria were pediatric patients, implementation of Enhanced Recovery After Surgery (ERAS) protocols, or non-elective neurosurgical procedures. The primary outcome was readmission rates after implementation of TCPs. RESULTS: 16 articles were included in this review. 2 articles found that patients treated with TCPs had significantly higher chances of home discharge. 7 articles found a significant association between implementation of TCP and reduced length of stay and intensive care unit stay. 3 articles reported an increase in patient satisfaction after implementation of TCPs. 3 found that TCP led to a significant decrease in readmissions. After meta-analysis, TCPs were associated with significantly decreased readmission rates (OR: 0.68, p < 0.0001), length of stay (mean difference: -0.57, p < 0.00001), and emergency department visits (OR: 0.33, p < 0.0001). CONCLUSIONS: This systematic review and meta-analysis found that an overwhelming majority of the available literature supports the effectiveness of discharge planning on at least one measure of patient outcomes. However, the extent to which each facet of the TCP affects outcomes in elective neurosurgery remains unclear. Future efforts should be made to compare the effectiveness of different TCPs.

NFĸB signaling drives myocardial injury via CCR2+ macrophages in a preclinical model of arrhythmogenic cardiomyopathy.

Nuclear factor κ-B (NFκB) is activated in iPSC-cardiac myocytes from patients with arrhythmogenic cardiomyopathy (ACM) under basal conditions, and inhibition of NFκB signaling prevents disease in Dsg2mut/mut mice, a robust mouse model of ACM. Here, we used genetic approaches and single-cell RNA-Seq to define the contributions of immune signaling in cardiac myocytes and macrophages in the natural progression of ACM using Dsg2mut/mut mice. We found that NFκB signaling in cardiac myocytes drives myocardial injury, contractile dysfunction, and arrhythmias in Dsg2mut/mut mice. NFκB signaling in cardiac myocytes mobilizes macrophages expressing C-C motif chemokine receptor-2 (CCR2+ cells) to affected areas within the heart, where they mediate myocardial injury and arrhythmias. Contractile dysfunction in Dsg2mut/mut mice is caused both by loss of heart muscle and negative inotropic effects of inflammation in viable muscle. Single nucleus RNA-Seq and cellular indexing of transcriptomes and epitomes (CITE-Seq) studies revealed marked proinflammatory changes in gene expression and the cellular landscape in hearts of Dsg2mut/mut mice involving cardiac myocytes, fibroblasts, and CCR2+ macrophages. Changes in gene expression in cardiac myocytes and fibroblasts in Dsg2mut/mut mice were dependent on CCR2+ macrophage recruitment to the heart. These results highlight complex mechanisms of immune injury and regulatory crosstalk between cardiac myocytes, inflammatory cells, and fibroblasts in the pathogenesis of ACM.

Deciphering the Neuropsychiatric Lupus Enigma: Navigating the Intersection of Acute Inflammatory Demyelinating Polyneuropathy (AIDP), Infection, and Flare.

A 17-year-old male diagnosed with systemic lupus erythematosus (SLE), showing poor compliance with medication, presented to our facility with a 20-day history of fever, polyarthritis, and cough. Additionally, he had experienced a seizure episode, followed by a one-day history of altered mentation. Subsequently, he developed pneumonia, respiratory distress, and shock, necessitating ventilator and inotropic support. Neuropsychiatric lupus (NP-lupus) was suspected, and hence high-dose steroids, hydroxychloroquine, and broad-spectrum antibiotics were initiated. Following successful extubation, he manifested ascending flaccid paralysis. The presence of albumin-cytological dissociation and axonal neuropathy confirmed the diagnosis of acute inflammatory demyelinating polyneuropathy (AIDP). He underwent further management with pulse steroids and plasmapheresis. Upon recovery, he was discharged on a regimen of steroids, cyclophosphamide, and hydroxychloroquine. During follow-up, he maintained ambulatory status with no residual neurological sequelae.

Anaerobic growth and drug susceptibility of versatile fungal pathogen Scedosporium apiospermum.

Although severe cases of invasive mycoses of different hypoxic and anoxic body parts have been reported, growth and drug susceptibility of fungal pathogens under anaerobic conditions remains understudied. The current study evaluated anaerobic growth potential and drug susceptibility of environmental Scedosporium apiospermum isolates under aerobic and anaerobic conditions. All tested strains showed equivalent growth and higher sensitivity to tested antifungal drugs under anaerobic conditions with lower minimum inhibitory concentration (MIC) as compared to aerobic conditions. Antifungal azoles were effective against isolates under both aerobic and anaerobic conditions. Most strains were resistant to antifungal echinocandins and polyenes under aerobic conditions but exhibited sensitivity under anaerobic conditions. This study provides evidence that resistance of S. apiospermum to antifungal drugs varies with oxygen concentration and availability and suggests re-evaluating clinical breakpoints for antifungal compounds to treat invasive fungal infections more effectively.

Glycopyrrolate-induced polyuria: An unexpected side effect.

Polyuria is urine output exceeding 3 L/d in adults, primarily due to solute and water diuresis. In a hospital setting, mannitol and diuretics commonly lead to polyuria. We have found an interesting association of polyuria with glycopyrrolate; to the best of our knowledge, no case is reported in the literature. Here, we are describing a case of Guillain-Barre Syndrome, which developed polyuria during the hospital stay, which was secondary to glycopyrrolate.

Metabolomic Profiling of Asparagine Deprivation in Asparagine Synthetase Deficiency Patient-Derived Cells.

The natural amino acid asparagine (Asn) is required by cells to sustain function and proliferation. Healthy cells can synthesize Asn through asparagine synthetase (ASNS) activity, whereas specific cancer and genetically diseased cells are forced to obtain asparagine from the extracellular environment. ASNS catalyzes the ATP-dependent synthesis of Asn from aspartate by consuming glutamine as a nitrogen source. Asparagine Synthetase Deficiency (ASNSD) is a disease that results from biallelic mutations in the ASNS gene and presents with congenital microcephaly, intractable seizures, and progressive brain atrophy. ASNSD often leads to premature death. Although clinical and cellular studies have reported that Asn deprivation contributes to the disease symptoms, the global metabolic effects of Asn deprivation on ASNSD-derived cells have not been studied. We analyzed two previously characterized cell culture models, lymphoblastoids and fibroblasts, each carrying unique ASNS mutations from families with ASNSD. Metabolomics analysis demonstrated that Asn deprivation in ASNS-deficient cells led to disruptions across a wide range of metabolites. Moreover, we observed significant decrements in TCA cycle intermediates and anaplerotic substrates in ASNS-deficient cells challenged with Asn deprivation. We have identified pantothenate, phenylalanine, and aspartate as possible biomarkers of Asn deprivation in normal and ASNSD-derived cells. This work implies the possibility of a novel ASNSD diagnostic via targeted biomarker analysis of a blood draw.

Minimally Invasive Transforaminal Lumbar Interbody Fusion in the Ambulatory Setting with an Enhanced Recovery After Surgery Protocol.

OBJECTIVE: Enhanced Recovery After Surgery (ERAS) is a multidisciplinary approach to surgical care that aims to improve outcomes and reduce costs. Its application to spine surgery has been increasing in recent years, with a notable focus on lumbar fusion. This study describes the development, implementation, and outcomes of the first ERAS pathway for ambulatory spine surgery and the largest ambulatory minimally invasive transforaminal lumbar interbody fusion (MIS TLIF) series to date. METHODS: A comprehensive protocol for ambulatory lumbar fusion is described, including patient selection criteria, a multimodal analgesia regimen, and discharge assessment. Consecutive patients undergoing 1- or 2-level MIS TLIF using the described protocol at a single ambulatory surgery center (ASC) over a five-year period were queried. RESULTS: A total of 215 patients underwent ambulatory MIS TLIF over the study period. There were no intraoperative or immediate postoperative complications. All but one patient (99.5%) were discharged home from the ASC. Almost three-quarters (71.2%) were discharged on the day of surgery. Thirty- and 90-day readmission rates were 1.4% and 2.8%, respectively. Only one readmission (0.5%) was for intractable back pain. There were no reoperations or mortalities within 90 days of surgery. CONCLUSIONS: MIS TLIF can be performed safely in a freestanding ambulatory surgery center with minimal perioperative and short-term morbidity. The addition of comprehensive ERAS protocols to the ambulatory setting can promote the transition of fusion procedures to this lower cost environment in an effort to provide higher value care.

Efficacy of Intravenous Clonidine Premedication in the Prevention of Adverse Hemodynamic Changes During Intubation in Patients Undergoing Laparoscopic Surgery in Comparison with Placebo.

Context: Laparoscopic surgeries involve the creation of pneumoperitoneum, which produces significant hemodynamic changes. Alpha-2 adrenergic receptor agonists like clonidine are used as adjuvants during aesthesia for analgesic, sedative, sympatholytic and cardiovascular stabilizing effects. Aims: This study aims to assess the efficacy of intravenous (i.v.) clonidine premedication in the prevention of adverse hemodynamic changes during intubation in a patient undergoing laparoscopic surgery in comparison with (normal saline) placebo. Settings and Design: Eighty patients undergoing elective laparoscopic surgery were randomly assigned into two groups to receive either clonidine 3 µg.kg-1 diluted in normal saline or an equivalent quantity of normal saline administered intravenously 20 min before surgery. Materials and Methods: The primary outcome was to compare the efficacy of clonidine premedication in the prevention of adverse hemodynamic changes during intubation in patients undergoing laparoscopic surgery. Other outcome parameters observed were requirements of induction agents and intraoperative analgesia and postoperative adverse effects. Statistical Analysis Used: Analysis of variance has been used to find the significance of study parameters between three or more groups of patients; Chi-square/Fisher exact test has been used to find the significance of study parameters on a categorical scale between two or more groups. Results: Heart rate reduced significantly after 10 min 3 µg.kg-1 clonidine administration and the decrease persisted throughout induction and intubation. The fluctuations of systolic, diastolic, and mean arterial pressures were high in the control group when compared with the clonidine group, throughout induction and intubation. Conclusions: Premedication with i.v. clonidine is a relatively safe and effective method that provides stable hemodynamics and protection against stress responses induced during laryngoscopy and intubation in patients undergoing laparoscopic surgery.

Steroid and sphingomonas.

Sphingomonas paucimobilis is a Gram-negative bacteria identified as a rare infectious agent, more commonly seen among immune-compromised hosts. Infections include bacteremia, septicemia leading to septic shock, bone and soft-tissue infections such as septic arthritis, osteomyelitis, infection of shunts, and implantable devices. Although the organism has been reported to have low pathogenicity, infections in the immune compromised can be devastating leading to even death.

Résumé Sphingomonas paucimobilis est une bactérie Gram-négative identifiée comme un agent infectieux rare, plus fréquemment observé chez les hôtes immunodéprimés. Les infections comprenaient la bactériémie, la septicémie entraînant un choc septique, les infections des os et des tissus mous telles que l'arthrite septique, l'ostéomyélite, l'infection des shunts et des dispositifs implantables. Bien que l'organisme ait été signalé comme ayant une faible pathogénicité, les infections chez les personnes immunodéprimées peuvent être dévastatrices et même entraîner la mort. Mots clés: Sphingomonas, stéroïdes, antibiotiques.

Burden of pain in back and extremities in rural population: A community-based estimation of 12-month prevalence, distribution and duration of pain in rural Gadchiroli, India.

BACKGROUND: Population based estimates of the burden of pain in back and extremities (PBE) are lacking from rural India. We estimated this burden, measured as a) 12-month prevalence, b) site specific prevalence c) total number of painful sites per adult, d) severity of pain and e) duration of pain in the rural adult population in Gadchiroli, India, over a period of 12 months. METHODS: This population-based, cross-sectional study was conducted in two villages randomly selected from a cluster of 7 eligible villages in Gadchiroli district of India. All adults ≥20 years in these villages were surveyed by the trained community health workers in January 2010 by making household visits. The data were collected using a structured, pretested questionnaire on the history of pain in back and extremities (PBE) at various anatomical sites and its features during the previous 12 months. RESULTS: Out of 2535 eligible adults in two villages, 2259 (89%) were interviewed, of which 1876 (83%) had an episode of PBE in the preceding 12 months. The period prevalence of pain was 76% in back (including lower back, thoracic and neck) and 71% in the extremities. Highest site specific prevalence was at lower back (70%), knee (46%), neck (44%), leg/calf (39%) and mid-back (39%). The mean number of painful sites per adult was 4.57 (standard deviation (SD) = 4.17). The prevalence of severe pain was 15%. The mean number of painful days due to PBE was 166 days. Female gender (odds ratio (OR) = 2.8, 95% confidence interval (CI) = 2.1-3.6), farming/labour occupation (OR = 1.8, 95% CI = 1.4-2.4), increasing age (more than 60 years OR = 6.3, 95% CI = 3.3-11.9) were significantly associated with the risk of PBE. CONCLUSION: Nearly five out of six adults in rural Gadchiroli suffered from pain in back or extremities during the preceding 12 months. Pain was at multiple sites and was present on a mean 166 days in the year. Female gender, farming / manual labor as occupation and increasing age were the key risk factors identified. The pain in back and extremities emerges as a public health priority in rural communities.

Activity limitation and disability due to pain in back and extremities in rural population: A community-based study during a period of twelve months in rural Gadchiroli, India.

BACKGROUND: Population based estimates of the extent of the activity limitation due to back pain and disability due to musculoskeletal pains are lacking from rural India. We estimated this burden as a) extent of activity limitation due to back pain, b) disability due to musculoskeletal pains, c) grading of the limitation of each activity due to back and musculoskeletal pain in the rural adult population in Gadchiroli, India. METHODS: This population-based, cross-sectional study was conducted in two villages randomly selected from a cluster of 7 eligible villages in Gadchiroli district of India. All adults ≥20 years in these villages were surveyed by the trained community health workers in January 2010. Disability due to back pain was evaluated using newly developed questionnaire for women and men which assessed limitations in the gender-specific daily household and occupational activities in a rural area. Disability due to pain in extremities was assessed using the Health Assessment Questionnaire (HAQ). RESULTS: The total population of the two villages was 3735 out of which 2535 (67.9%) were adults ≥20 years of age and were eligible to participate in the study. Of these, 2259 (89%) were interviewed and 1247 participants (55%) had any pain on the day of the survey. Activity limitation questionnaire was filled for 716 (91.4%) out of 783 patients with back pain. HAQ scale was filled for 524 (85.2%) out of 615 patients with pain in extremities. Among men with back pain, respectively 11%, 19%, 60% and 11% had no, mild, moderate to severe difficulty or were completely unable to perform agrarian work, while among women, respectively 6%, 20%, 69% and 4% had no, mild, moderate to severe difficulty or were completely unable to perform household activities. Based on the HAQ score, respectively 1%, 67%, 18% and 14% of the participants had no, mild, moderate to severe disability or were completely unable to perform the activities. CONCLUSIONS: This community-based study in rural Gadchiroli demonstrates significant mild to moderate disability and activity limitation, due to pain in back and extremities in a population involved in hard manual work, especially agricultural and underlines the need to address the problem through appropriate interventions. The study also employs for the first time an indigenously developed questionnaire to identify activity limitation due to back pain, and demonstrates the method as well as the questionnaire.

Clinical patterns and their prevalence among adult population with back pain: A community-based cross-sectional study in rural Gadchiroli, India.

BACKGROUND: Evaluating clinical patterns and their prevalence of back pain, a common problem in rural areas, can help develop treatment strategies to address this leading cause of disability. METHODS: We conducted a population-based study in rural Gadchiroli, India. In this, two-phase study, trained surveyors conducted a door to door survey (Phase 1) to identify individuals with pain in the back and extremities in two villages randomly selected using pre-defined criteria. Those with pain were evaluated by a team of spine surgeons and rheumatologists to diagnose clinical conditions among these patients (Phase 2). RESULTS: Of the 2535 eligible adults, 2259 (89%) were screened, 1247 (55%) reported pain in back and limb and were referred to the specialist clinic. Out of the 906 (73%) participants who attended the clinics, 783 (89%) had back/neck pain. The point prevalence of back/neck pain among adults was 49% (95% confidence interval (CI) = 49%-51%), non-specific low back pain 45% (95% CI = 43.4%-47.5%); non-specific neck pain 21% (95% CI = 18.9-22.4), radiculopathy 12 (95% CI = 10.4-13.1), myelopathy 0.4 (95% CI = 0.1-0.7) and other serious spinal disorders 0.2 (95% CI 0.048-0.45). The prevalence of non-specific back/neck pain and radiculopathy was higher among females. CONCLUSIONS: Non-specific back and neck pain are the commonest diagnoses among those with pain in the back and extremities, followed by radiculopathy. Serious disorders are rare. Given the high prevalence of non-specific back and neck pain, community health workers and physicians working in rural areas need to be trained systematically to manage these conditions.

Epidemiology of pain in back and extremities in rural population: A community-based estimation of age- and sex-specific prevalence, distribution, duration and intensity of pain, number of painful sites and seasonality of pain during twelve months in rural Gadchiroli, India.

BACKGROUND: Population-based estimates of the burden of pain in back and extremities (PBE) by sex, age, intensity, seasonality and site are lacking from rural India. METHODS: Two villages were randomly selected from a cluster of 39 villages in Gadchiroli district in India. All residents'≥20 years of age were surveyed in January 2010 by trained surveyors by making household visits. Information on PBE in the 12 months prior to survey was obtained using a structured, pretested questionnaire. RESULTS: The 12-month period prevalence of PBE was 75% (95% confidence interval CI = 72.54-77.73) in men and 91% (95% CI = 88.66-92.13) in women. The prevalence of PBE in the participants >50 years was 94% while that in the age group 20 to 50 years was 79% (P < 0.05). The site with the highest prevalence of pain was low back (women 80%, men 59%). The mean number of painful sites per person was 5.42 (95% CI = 5.17-5.67) in women, 3.68 (95% CI = 3.45-3.90) in men, 3.89 (95% CI = 3.71-4.07) in participants aged 20 to 50 years and 6.48 (95% CI = 6.11-6.85) in those >50 years. Among participants across the age and sex groups, the prevalence of mild pain was higher than severe pain at all the anatomical sites. Among various seasons, the highest prevalence of pain was in the rainy season (14%). CONCLUSION: The prevalence and the number of painful sites were higher among women and in those >50 years of age. The public health interventions for PBE need to focus on these two high risk groups.

Wilson's Disease: Diagnosis in Novel Way.

Wilson's disease first described by Kinnier Wilson in 1912, is a rare autosomal recessive genetic disorder involving a defect in copper metabolism. This disease affects between one in 30,000 to one in 100,000 individuals and has a carrier frequency of one in every 90. It is characterized by hepatic and neurological symptoms. The usual age of presentation is 4 to 40 years but this disorder has been detected in children as young as three years and adults as old as 70 years with males and females being equally affected. Diagnosing Wilson's disease at the earliest is crucial as it is not only progressive and fatal if untreated, but also responds promptly to medication. Here we are going to present a novel way to diagnose a case of Wilson disease in a resource-limited setting. The diagnosis was possible with detailed present and past history raising strong clinical suspicion of environmental or genetically related disease. The diagnosis was done in a novel way by first diagnosing in daughter thereafter confirming the same diagnosis in patient.

Single and double scattering event analysis for ultraviolet communication channels.

This paper presents a channel analysis method for single and double scattering events in non-line-of-sight (NLOS) ultraviolet (UV) communication systems. In general, the calculations of path loss and impulse response of such systems require Monte Carlo random number generations. However, the high computational costs of Monte Carlo methods impose severe limitations on quick reliable evaluations of system performance under complex atmospheric conditions. This paper proposes a sample-based UV channel characterization approach that improves computational performance by multiple orders of magnitude. The proposed novel approach uses fixed probability-based sampling. The method focuses only on single and double scattering events which dominate the received signal. The effects of various fog and dust aerosols are discussed under non-planar realistic conditions. The results demonstrate reliable channel characterization with significantly lower complexity using the proposed approach.

Pre-hospital care and its association with clinical outcome of snakebite victims presenting at a tertiary care referral hospital in South India.

Most snakebite victims in low- and middle-income countries continue to seek many forms of first aid therapy before reaching hospital, the commonest being the application of a tourniquet. Our study looked at a prospective cohort of 382 such patients to ascertain the association of pre-hospital care with clinical outcome, and found that 60% developed complications as compared to 36% who had no pre-hospital care (p < 0.001), with 10 fatalities in the former compared to only one in the latter. Pre-hospital care remains very common and definitely increases morbidity and mortality.

Association between carbonyl stress markers and the risk of acute coronary syndrome in patients with type 2 diabetes mellitus-A pilot study.

BACKGROUND AND AIMS: Carbonyl stress is one of the mechanisms responsible for diabetes and its complications. The study was planned to examine the relationship between carbonyl stress markers and the risk of acute coronary syndrome (ACS) in patients with type 2 diabetes mellitus (T2DM). METHODS: Forty T2DM patients with ACS and forty T2DM patients without ACS participated in this cross-sectional pilot study. Routine biochemical investigations, creatine kinase-total (CK-T), and creatine kinase-MB (CK-MB) levels were estimated. Serum carbonyl stress markers were analysed by enzyme-linked immunosorbent assay. Binary logistics regression was done to determine the predictive value of carbonyl stress markers for ACS. RESULTS: Fasting plasma glucose, serum total methylglyoxal (MG), methylglyoxal derived hydroimidazolones-1 (MG-H1), and Nε-carboxymethyl-lysine (CML) levels were significantly higher in T2DM patients with ACS than in those without ACS. Serum glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glyoxalase-1 (GLO1) levels were significantly lower in T2DM patients with ACS than in those without ACS. Fasting plasma glucose level was significantly positively correlated with serum MG (r = 0.441, P < 0.001), CML (r = 0.649, P < 0.001), MG-H1 (r = 0.725, P < 0.001), and negatively correlated with serum GAPDH (r = - 0.268, P = 0.012) and GLO1 (r = - 0.634, P = 0.016). Receiver operating characteristic curve analysis showed that serum GAPDH and GLO1 could predict the risk of ACS in T2DM patients. CONCLUSION: These findings revealed that high carbonyl stress due to lower levels of GAPDH and GLO1 may predispose patients with T2DM for more risk of ACS.