ABSTRACT
OBJECTIVES: This study explored the hypothesis that social determinants of health (SDOH), including racial and economic differences, may impact orthopaedic trauma outcomes in patients undergoing open reduction and internal fixation (ORIF) of humeral shaft fractures. METHODS: Design: Retrospective. SETTING: Single, academic, tertiary Level-I trauma center. PATIENT SELECTION CRITERIA: Adults with midshaft humerus fractures (AO/OTA 12) treated operatively with plate fixation from 05/2011 to 05/2021 with a minimum follow-up of nine months. OUTCOME MEASURES AND COMPARISONS: Radiographic fracture healing, complication rates, and patient-reported outcomes were investigated. SDOH were assessed using the Area Deprivation Index (ADI). Demographics, complications rates, and patient-reported clinical outcomes were compared between the first and fourth ADI quartiles. RESULTS: 196 patients fit the study criteria. The average age of the cohort was 47 years with 50 women (51%). Comparisons of the least deprived quartile (n=49) to the most deprived quartile (n=49) yielded similar sex distribution (59% vs 43% female, p=0.15), fewer non-white patients (8% vs 51%, p<0.01), older average age (51 years vs 43 years, p=0.05), similar BMI (30.5 vs. 31.8, p=0.45), and higher Charlson Comorbidity Index (CCI) (2.2 vs.1.1, p=0.03). While nonunion rates were similar (p=0.20) between groups, the most deprived quartile had 2.3 times greater odds of post-operative complications (p=0.04). Patients in the most deprived group exhibited higher PROMIS Pain Interference (PI) scores (p<0.01) and PROMIS Depression (D) scores (p=0.01), with lower PROMIS Physical Function (PF) scores (p<0.01) at 6-month follow-up than the least depriver cohort. The most deprived cohort had three times higher odds of missing scheduled appointments within the first post-operative year (p<0.01), resulting in a significantly higher no-show rate (p<0.01) than the least deprived cohort. Regression analysis including several demographic and injury factors identified that ADI was significantly associated with the occurrence of any missed appointments (p<0.01), no-show rates (p=0.04), and experiencing one of the following post-operative complications during recovery: Nonunion, radial nerve injury, or dysfunction (p=0.03). CONCLUSIONS: Patients experiencing greater resource deprivation faced increased odds of complications, missed appointments, and poorer PROMIS outcomes following humeral shaft fracture fixation, emphasizing that baseline socioeconomic disparities predict unfavorable post-operative outcomes even given favorable baseline health status according to the CCI score. LEVEL OF EVIDENCE: Level III. See Instructions for Authors for a complete description of levels of evidence.
ABSTRACT
The mitochondrial permeability transition pore (mPTP) is a supramolecular channel that regulates exchange of solutes across cristae membranes, with executive roles in mitochondrial function and cell death. The contribution of the mPTP to normal physiology remains debated, although evidence implicates the mPTP in mitochondrial inner membrane remodeling in differentiating progenitor cells. Here, we demonstrate that strict control over mPTP conductance shapes metabolic machinery as cells transit toward hematopoietic identity. Cells undergoing the endothelial-to-hematopoietic transition (EHT) tightly control chief regulatory elements of the mPTP. During EHT, maturing arterial endothelium restricts mPTP activity just prior to hematopoietic commitment. After transition in cellular identity, mPTP conductance is restored. In utero treatment with NIM811, a molecule that blocks sensitization of the mPTP to opening by Cyclophilin D (CypD), amplifies oxidative phosphorylation (OXPHOS) in hematopoietic precursors and increases hematopoiesis in the embryo. Additionally, differentiating pluripotent stem cells (PSCs) acquire greater organization of mitochondrial cristae and hematopoietic activity following knockdown of the CypD gene, Ppif. Conversely, knockdown of Opa1, a GTPase critical for proper cristae architecture, induces cristae irregularity and impairs hematopoiesis. These data elucidate a mechanism that regulates mitochondrial maturation in hematopoietic precursors and underscore a role for the mPTP in the acquisition of hematopoietic fate.
Subject(s)
Hematopoietic Stem Cells , Mitochondria , Mitochondrial Permeability Transition Pore , Animals , Mitochondria/metabolism , Hematopoietic Stem Cells/metabolism , Mitochondrial Permeability Transition Pore/metabolism , Mice , Mitochondrial Membrane Transport Proteins/metabolism , Mitochondrial Membrane Transport Proteins/genetics , Hematopoiesis , Peptidyl-Prolyl Isomerase F/metabolism , Peptidyl-Prolyl Isomerase F/genetics , Cell Differentiation , Oxidative Phosphorylation , Female , Mice, Inbred C57BLABSTRACT
BACKGROUND: Cerebrospinal fluid creatine kinase BB isoenzyme (CSF CK-BB) after cardiac arrest (CA) has been shown to have a high positive predictive value for poor neurological outcome, but it has not been evaluated in the setting of targeted temperature management (TTM) and modern CA care. We aimed to evaluate CSF CK-BB as a prognostic biomarker after CA. METHODS: We performed a retrospective cohort study of patients with CA admitted between 2010 and 2020 to a three-hospital health system who remained comatose and had CSF CK-BB assayed between 36 and 84 h after CA. We examined the proportion of patients at hospital discharge who achieved favorable or intermediate neurological outcome, defined as Cerebral Performance Category score of 1-3, compared with those with poor outcome (Cerebral Performance Category score 4-5) for various CSF CK-BB thresholds. We also evaluated additive value of bilateral absence of somatosensory evoked potentials (SSEPs). RESULTS: Among 214 eligible patients, the mean age was 54.7 ± 4.8 years, 72% of patients were male, 33% were nonwhite, 17% had shockable rhythm, 90% were out-of-hospital CA, and 83% received TTM. A total of 19 (9%) awakened. CSF CK-BB ≥ 230 U/L predicted a poor outcome at hospital discharge, with a specificity of 100% (95% confidence interval [CI] 82-100%) and sensitivity of 69% (95% CI 62-76%). When combined with bilaterally absent N20 response on SSEP, specificity remained 100% while sensitivity increased to 80% (95% CI 73-85%). Discordant CK-BB and SSEP findings were seen in 13 (9%) patients. CONCLUSIONS: Cerebrospinal fluid creatine kinase BB isoenzyme levels accurately predicted poor neurological outcome among CA survivors treated with TTM. The CSF CK-BB cutoff of 230 U/L optimizes sensitivity to 69% while maintaining a specificity of 100%. CSF CK-BB could be a useful addition to multimodal neurological prognostication after CA.
ABSTRACT
OBJECTIVES: To determine if rates of pin site infection and surgical site infection among patients managed with primary closure after external fixator removal were similar to those allowed to heal secondarily. DESIGN: Retrospective cohort. SETTING: Urban/Suburban Academic Level I Trauma Center. PATIENT SELECTION CRITERIA: Patients who had received a lower extremity external fixator for provisional management before definitive fixation of lower extremity fractures were included with pin site wounds closed primarily or allowed to heal by secondary intention. OUTCOME MEASURES AND COMPARISONS: The rate of pin tract infection and surgical site infection following primary closure of external fixator pin sites relative to patients whose pin sites were allowed to heal through secondary intention. RESULTS: In total, 256 patients were evaluated: 143 patients (406 pin sites) in the primary closure group and 113 patients (340 in sites) in the secondary closure group. The average age was 49 ± 16 years. Sixty-five percent of included patients were male. There was no difference in pin tract infections between cohorts (primary = 0.5%, secondary = 1.5%, P = 0.26). External fixator duration in the primary closure group was 11.5 ± 8.4 days and 13.0 ± 8.1 days in the secondary closure group (P = 0.15). There was a greater rate of surgical site infections in the secondary intention cohort (15.9% vs. 7.7%, P = 0.047). CONCLUSIONS: There was no difference in pin site infection rate after primary pin site closure relative to patients who were allowed to heal through secondary intention. Furthermore, there was a lower rate of surgical site infection after primary closure. These results challenge the dogma of secondary closure for ex fix pin sites, suggesting that debridement and primary closure is a safe option for management of external fixator pin sites and may impart benefit in decreasing infection risk. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Subject(s)
Bone Nails , External Fixators , Fracture Fixation , Surgical Wound Infection , Humans , Male , Female , Middle Aged , Surgical Wound Infection/etiology , Retrospective Studies , Adult , Fracture Fixation/instrumentation , Fracture Fixation/adverse effects , Fracture Fixation/methods , Fractures, Bone/surgery , Treatment Outcome , Device Removal , Aged , Wound Closure Techniques/instrumentation , Wound Closure Techniques/adverse effects , Cohort Studies , Acute Care SurgeryABSTRACT
CASE: A 58-year-old woman with medical history of a left total hip arthroplasty performed by the direct anterior (DA) approach 2 years prior presented with left hip pain. She was found to have sustained a transverse Vancouver C periprosthetic femur fracture and an unstable periprosthetic pelvic fracture. CONCLUSIONS: This patient's case represents a previously not reported injury about a total hip arthroplasty-with disruption distal to the femoral implant and proximal to the acetabular implant, with the implant-to-bone interface unaffected. This case may guide future treatment of similar injuries.
Subject(s)
Arthroplasty, Replacement, Hip , Periprosthetic Fractures , Humans , Female , Arthroplasty, Replacement, Hip/adverse effects , Middle Aged , Periprosthetic Fractures/surgery , Periprosthetic Fractures/etiology , Periprosthetic Fractures/diagnostic imaging , Femoral Fractures/surgery , Femoral Fractures/diagnostic imaging , Femoral Fractures/etiologyABSTRACT
Background: Zearalenone (ZEA), a natural food contaminant, is reported to act as a mycoestrogen due to its estrogen-mimicking properties. According to studies, ZEA has a greater potential for estrogenic activity compared to any other naturally occurring non-steroidal estrogen. ZEA has been found in the endometrium of individuals with reproductive problems and the serum of children facing early puberty. These studies suggested a possible link between ZEA exposure and endometrial toxicity; nonetheless, no thorough research has been done. This study assessed the endometrium's response to chronic ZEA exposure. Methods: Four groups of CD-1 female mice were exposed to control, estradiol (E2), and two different doses of ZEA for 90 days. At the end of treatment, blood and uterus were collected, and samples were used for inflammatory cytokines level, immunochemical, histopathological, and biophysical analysis. Results: Our data indicated that the uterus showed a change in body/organ weight ratio, while other organs did not have any notable changes. Immunochemical and histological studies showed hyperplasia and a higher number of glands in the endometrium after ZEA and E2 exposure. Similarly, proliferation markers such as proliferative cell nuclear antigen (PCNA), Ki-67, and inflammatory cytokines such as interleukin 6 (IL-6), interleukin 8 (IL-8), and interferon-gamma (IFN-?) levels were found to be higher in the E2 and ZEA-exposed groups. Conclusion: Our finding conclude that ZEA targets the uterus and cause inflammation due to increased levels of inflammatory cytokines and proliferation mediators, as well as systemic toxicity denoted by a strong binding affinity with serum proteins.
ABSTRACT
Coxiellosis in animals is caused by the zoonotic pathogen, Coxiella burnetii. Although the disease is of public health importance it remains underdiagnosed and underreported. The cross- sectional study was aimed to estimate the occurrence of the disease in livestock of study area and also to identify the risk factors associated with the disease in animals. Blood, serum, and vaginal swabs samples were collected from 200 ruminants (cattle, sheep, and goats), across various farms in Karnataka, India. These samples were then screened using ELISA and PCR (com1 and IS1111). A questionnaire was administered to the farm owners to collect the risk factor-related information. About 5.26 % cattle, 12.3 % sheep, and 12.5 % goats were positive by ELISA. By PCR, 9.47 % cattle, 9.3 % sheep, and 10 % goats were positive. Overall, the occurrence of 14.73 %, 18.46 % and 17.5 % was estimated in cattle, sheep and goat, respectively. PCR targeting the IS1111 gene detected higher number of samples as positive as compared to the com1 gene PCR. Higher number of vaginal swab samples were detected as positive as compared to blood. History of reproductive disorders (OR: 4.30; 95 %CI:1.95- 9.46), abortion (OR: 30.94; 95 %CI:6.30- 151.84) and repeat breeding (OR:11.36; 95 %CI:4.16- 30.99) were significantly associated with coxiellosis (p < 0.005). Multivariable analysis by logistic regression model analysis suggested retained abortion, repeat breeding and rearing of animal in semi-intensive system as factors significantly associated with the infection. Cultural identification of the PCR positive samples were cultured using embryonated egg propagation and cell culture techniques and positivity was confirmed in six samples. Phylogenetic analysis of the com1 and IS1111 gene revealed clustering based on similar geographic locations. The study estimated the occurrence of the disease in the study area and identified the potential risk factors.
Subject(s)
Cattle Diseases , Coxiella burnetii , Goat Diseases , Goats , Polymerase Chain Reaction , Q Fever , Sheep Diseases , Animals , Q Fever/epidemiology , Q Fever/veterinary , Q Fever/microbiology , Risk Factors , Coxiella burnetii/genetics , Coxiella burnetii/isolation & purification , Goats/microbiology , Sheep/microbiology , Cattle , Female , India/epidemiology , Cross-Sectional Studies , Goat Diseases/microbiology , Goat Diseases/epidemiology , Sheep Diseases/epidemiology , Sheep Diseases/microbiology , Cattle Diseases/epidemiology , Cattle Diseases/microbiology , Enzyme-Linked Immunosorbent Assay , Ruminants/microbiology , Surveys and Questionnaires , Vagina/microbiologyABSTRACT
OBJECTIVES: To test the hypothesis that primary osteosynthesis of humeral shaft fractures may lead to more favorable clinical, functional, and patient-reported outcomes than fixation following a trial of nonoperative management. DESIGN: Retrospective cohort review. SETTING: Academic level I trauma center. PATIENT SELECTION CRITERIA: Adult patients who presented with humeral shaft fractures and ultimately underwent open reduction and internal fixation (ORIF) from May 2011 to May 2021. Patients who underwent ORIF within 2 weeks of injury were grouped into the primary osteosynthesis cohort, and patients who underwent ORIF >4 weeks from the date of injury were grouped into the trial of nonoperative cohort. OUTCOME MEASURES AND COMPARISONS: Postoperative complications, elbow arc of motion, time to radiographic union, and patient-reported outcomes were investigated and compared between the primary osteosynthesis and trial of nonoperative management cohorts. RESULTS: One hundred twenty-seven patients fit the study criteria, 84 underwent primary osteosynthesis and 43 trialed initial nonoperative treatment. No differences were found in patient demographics between the primary osteosynthesis and trial of nonoperative management cohorts, including age (53 ± 19 vs. 57 ± 18; P = 0.25), sex (39% vs. 44% male, 61% vs. 56% female; P = 0.70), and Body Mass Index (BMI) (30 ± 6 vs. 32 ± 9; P = 0.38). The average time to operative intervention in the primary osteosynthesis group was 4 days (0-14 days) and 105 days (28-332 days) in the trial of nonoperative treatment group ( P < 0.01). No differences were found with regard to intraoperative blood loss, total operative time, time to radiographic union (determined using the Radiographic Union Scores for Humeral scoring system), or overall complication rates, including primary and secondary radial nerve injuries ( P = 0.23 and 0.86, respectively). Patients reported similar patient-reported outcomes measurement information system pain interference ( P = 0.73), depression (D) ( P = 0.99), and physical function ( P = 0.66) scores at their 6-month postsurgical follow-up visits. CONCLUSIONS: Patients who attempted a trial of nonoperative management for humeral shaft fractures before ORIF had similar clinical, functional, and patient-reported outcomes as those who underwent primary osteosynthesis. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Subject(s)
Fracture Fixation, Internal , Humeral Fractures , Open Fracture Reduction , Patient Reported Outcome Measures , Humans , Humeral Fractures/surgery , Humeral Fractures/therapy , Male , Female , Middle Aged , Fracture Fixation, Internal/methods , Open Fracture Reduction/methods , Retrospective Studies , Adult , Aged , Treatment Outcome , Cohort Studies , Conservative Treatment/methodsABSTRACT
The credo of the generalist physician has always been the promotion of health for all, in every aspect: not just multiple vulnerable organ systems, but multiple social, cultural, and political factors that contribute to poor health and exacerbate health inequity. In recent years, the field of global health has also adopted this same mission: working across both national and clinical specialty borders to improve health for all and end health disparities worldwide. Yet within the Society for General Internal Medicine, and among American generalists, engagement in global health, both within and outside the USA, remains uncommon. We see this gap as an opportunity, because in fact generalists in America already have the skills and experience that global health badly needs. SGIM could promote generalists to global health's vanguard, with three core steps. First, we generalists must continue to integrate health for the vulnerable into our domestic work, generating care models applicable in low-resource settings around the globe. Conversely, we must also engage with and implement international ideas and solutions for universal access to primary care for vulnerable patients in the USA. And lastly, we must build platforms to connect ourselves with colleagues worldwide to exchange these learnings.
Subject(s)
Global Health , Humans , General Practitioners , Primary Health Care/organization & administrationABSTRACT
The study comparatively evaluated serological assays, namely, Weil Felix assay, and IgM ELISA with the gold-standard immunofluorescence test (IFAT) for the sensitive and specific serodiagnosis of scrub typhus infection in occupationally exposed groups of humans. A total of 78 serum samples collected from persons affected with various ailments and belonging to different risk groups were screened in the study. Out of the 78 serum samples tested, a total of 17, 26, and 47 samples turned out to be positive by IFAT, IgM ELISA, and Weil Felix test, respectively. The Weil Felix assay could not serve as an ideal test for screening scrub typhus infection owing to its poor sensitivity and specificity in comparison with IFAT. IgM-ELISA could be an initial screening test to detect scrub typhus suspected patient in limited resource settings.
Subject(s)
Orientia tsutsugamushi , Scrub Typhus , Humans , Scrub Typhus/diagnosis , Enzyme-Linked Immunosorbent Assay , Sensitivity and Specificity , Immunoglobulin M , Antibodies, BacterialABSTRACT
Background: Operative decision making between approaches to posterior malleolus reduction remains a challenge. The purpose of this study is to compare the quality of reduction between percutaneous and open reduction of posterior malleolus fractures and to identify factors associated with malreduction. Methods: Operatively managed ankle fractures that included posterior malleolus fixation were reviewed. Fracture characteristics were determined on preoperative CT scans. Initial postoperative radiographs were used to measure reduction of the posterior malleolus articular surface and graded as satisfactory (<2 mm step-off) or malreduced (≥2 mm step-off). Final postoperative PROMIS scores and 1-year complications were compared between percutaneous and open cohorts. A multivariate stepwise regression model was used to evaluate predictors for malreduction. Results: A total of 120 patients were included. Open reduction was performed in 91 (75.8%) compared with 29 (24.2%) who underwent percutaneous reduction. Malreduction (≥2-mm articular step-off) occurred in 11.7% of patients. Malreduction rates were significantly higher with percutaneous fixation than open fixation (24.1% vs 7.7%, P = .02). Multiple fragments and those with ≥5 mm of displacement demonstrated higher malreduction rates with percutaneous fixation (P < .05 for both), whereas single fragments and those with <5 mm of displacement experienced similar malreduction rates with percutaneous or open fixation. Initial displacement ≥5 mm (relative risk [RR] = 3.8, 95% CI = 1.2-11.5, P = .02) and percutaneous treatment (RR = 4.1, 95% CI = 1.6-10.5, P < .01) were identified as independent risk factors for malreduction. There were no significant differences in 1-year complication rates or final PROMIS scores between groups. Conclusion: Open reduction of the posterior malleolus may lead to improved fracture reduction compared to percutaneous reduction without significant increase in complications. Open fixation improves reduction among fractures with multiple fragments or ≥5 mm of displacement, whereas fractures with a single fragment or <5 mm of displacement achieve similar reductions regardless of approach. Initial displacement ≥5 mm and percutaneous reduction are independent risk factors for malreduction. Level of evidence: Level III, therapeutic.
ABSTRACT
BACKGROUND: The purpose of this study was to understand the role of social determinants of health assessed by the Area Deprivation Index (ADI) on hospital length of stay and discharge destination following surgical fixation of pelvic ring fractures. METHODS: A retrospective chart analysis was performed for all patients who presented to our level-I trauma center with pelvic ring injuries that were treated with surgical fixation. Social determinants of health were determined via use of the ADI, a comprehensive metric of socioeconomic status, education, income, employment, and housing quality. ADI values range from 0 to 100 and are normalized to a U.S. mean of 50, with higher scores representing greater social deprivation. We stratified our cohort into 4 ADI quartiles. Statistical analysis was performed on the bottom (25th percentile and below, least deprived) and top (75th percentile and above, most deprived) ADI quartiles. Significance was set at p < 0.05. RESULTS: There were 134 patients who met the inclusion criteria. Patients in the most deprived group were significantly more likely to have a history of smoking, to self-identify as Black, and to have a lower mean household income (p = 0.001). The most deprived ADI quartile had a significantly longer mean length of stay (and standard deviation) (19.2 ± 19 days) compared with the least deprived ADI quartile (14.7 ± 11 days) (p = 0.04). The least deprived quartile had a significantly higher percentage of patients who were discharged to a resource-intensive skilled nursing facility or inpatient rehabilitation facility compared with those in the most deprived quartile (p = 0.04). Race, insurance, and income were not significant predictors of discharge destination or hospital length of stay. CONCLUSIONS: Patients facing greater social determinants of health had longer hospital stays and were less likely to be discharged to resource-intensive facilities when compared with patients of lesser social deprivation. This may be due to socioeconomic barriers that limit access to such facilities. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.
Subject(s)
Fractures, Bone , Residence Characteristics , Humans , Length of Stay , Retrospective Studies , Social Class , Income , Fractures, Bone/surgeryABSTRACT
Meeting the requirement of high specific activity of radioisotopes and carrying out comprehensive research and development activities in the nuclear field, different nuclear facilities, including their waste disposal facilities, are going to be operational at Visakhapatnam, India. Due to environmental processes, the engineered disposal modules may lose their structural integrity and may release some radioactivity to the geo-environment. The subsequent migration of radionuclides reaching the geological environment will be governed by the distribution coefficient (Kd). Cs was chosen for the sorption study in two soil samples (soil-29 and 31) and to estimate the Kd in all the 40 soil samples through the laboratory batch method at the new campus of DAE, Visakhapatnam, India. Different soil chemical parameters like pH, organic matter, CaCO3, and cation exchange capacity were determined in 40 soil samples and their effect on Cs sorption was investigated. The effect of solution pH and initial concentration of Cs on sorption was also studied. The results show that the sorption of Cs increases with increasing pH. The Cs sorption was well explained by Freundlich and Dubinin-Radushkevich (D-R) isotherm models. Site-specific distribution coefficients (Kd) were also estimated and the values were found to vary from 75 ± 1 to 540 ± 12 L kg-1. The observed wide variation in Kd could be due to large variations in the physico-chemical properties of collected soil. The competitive ions effect study suggests that K+ has higher interference for Cs+ sorption as compared to Na+. The present study results will help assess the environmental impact due to Cs release in any unforeseen scenario and in planning effective remediation strategies.
Subject(s)
Soil Pollutants, Radioactive , Soil Pollutants , Adsorption , Environmental Monitoring , Soil Pollutants, Radioactive/analysis , Soil Pollutants/analysis , Soil/chemistry , IndiaABSTRACT
Introduction: Uncommon complication of Monteggia fracture is associated PIN palsy. The PIN palsy following Monteggia fracture-dislocation is neuropraxias and will recover spontaneously. Case Report: Two cases who were diagnosed as Monteggia fracture-dislocation with PIN palsy and associated superficial branch of radial nerve injury - Power 0/5 and sensations 0/2 were taken up for surgery (open reduction internal fixation of fracture of ulna + closed reduction of radial head). By the end of 7 weeks, both sensory and motor power were fully recovered spontaneously in both the cases. Discussion: Most of the PIN injuries following Monteggia fracture-dislocation are neuropraxias and will recover spontaneously after closed reduction of radial head without any intervention to the nerve. The nerve needs to be intervened if there are no signs of recovery by 3 months. The time frame for the nerve to be intervened remains controversial. Conclusion: In both of our cases, the injury is probably proximal to the terminal division of radial nerve and the injuries were neuropraxias and have recovered spontaneously. Hence, we suggest not exploring the nerve in all cases with Monteggia fracture-dislocation immediately even when there is associated sensory deficit.
ABSTRACT
Leprosy is a leading cause of disability in India. The percentage of disability and deformity can be reduced by diagnosing leprosy at an early stage. In order to detect the hidden leprosy cases, leprosy case detection campaigns, on line with Pulse Polio Campaign have been introduced specifically for high endemic districts, by the Central Leprosy Division. Records of cases from 2018 to 2020 were evaluated retrospectively to study the trend of new cases. The present study denotes the presence of hidden undiagnosed cases in the community and will require an intensification of leprosy control activities through contact tracing and active case detection. Continued quality surveillance is required for early detection, timely management, and prevention of the spread of the disease.
Subject(s)
Disabled Persons , Leprosy , Humans , Retrospective Studies , India/epidemiology , Leprosy/diagnosis , Leprosy/epidemiology , Leprosy/prevention & controlABSTRACT
Alzheimer's disease is among the major health challenges that currently attract the attention of health care givers and drug discovery and development experts worldwide. This study investigated the acetylcholinesterase inhibitory activity of sappanin-type homisoflavonoids isolated from the inter-bulb surface of Scilla nervosa. Molecular docking, molecular dynamics simulation, ADMET and in vitro studies were performed to identify the hit molecules, understand their binding mode and interaction, druggability and establish their inhibitory potentials against acetylcholinesterase enzyme. The hit compounds 5, 2, 1 and 4 were identified as the hit molecules through the molecular docking. The molecular dynamics simulation and MM-PBSA analysis showed the hit homoisoflavonoids established stability and good binding affinity against the acetylcholinesterase enzyme. Also, 5 elicited the best inhibitory activity followed by 2, 1 and 4 in the in vitro experiment. Furthermore, the selected homoisoflavonoids exhibit interesting drug likeness and pharmacokinetic properties as drug candidate. The results suggest further investigations towards the development of the phytochemicals as possible acetylcholinesterase inhibitors.Communicated by Ramaswamy H. Sarma.
Subject(s)
Acetylcholinesterase , Scilla , Humans , Acetylcholinesterase/chemistry , Molecular Docking Simulation , Scilla/metabolism , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/chemistry , Molecular Dynamics SimulationABSTRACT
Background: In the recent years, there has been a rapid increase in the use of robot assisted neck dissection (RAND) as an alternative method for conventional neck dissection. Several recent reports have emphasized upon the feasibility and effectiveness of this technique. However, substantial technical and technological innovation is still essential in spite of the availability of multiple approaches for RAND. Materials and Methods: The present study describes a novel technique, i.e., Robotic Infraclavicular Approach for Minimally Invasive Neck Dissection (RIA MIND) used in head and neck cancers with the help of Intuitive da Vinci Xi Surgical System. Results: After RIA MIND procedure, the patient was discharged on the third post operative day. Also, the total wound size was less than 3.5 cm which enhanced the patient recovery time and required minimal post operative care. The patient was further reviewed 10 days after the procedure for the removal of sutures. Conclusion: RIA MIND technique was effective and safe for performing neck dissection for oral, head and neck cancers. However, additional detailed studies will be required for establishing this technique.
ABSTRACT
A series of Michael adducts of malononitrile and sulfonamide chalcones were synthesized, characterized, and evaluated for their antifilarial activity. Out of 14 compounds, N-(4-(4,4-dicyano-3-p-tolylbutanoyl)phenyl)benzenesulfonamide showed favorable drug-likeness properties with marked antifilarial effects at micro-molar dosages. Apoptosis in Brugia malayi microfilariae was confirmed by EB/AO staining, MTT assay, and cytoplasmic cytochrome c ELISA. Since chalcone and folate synthesis pathways share the same substrate, we hypothesize a structural analogy-based inhibition of folate metabolism by this compound. Molecular docking against a pre-validated BmDHFR protein showed more favorable thermodynamic parameters than a positive control, epicatechin-3-gallate. The compound significantly suppressed the DHFR activity in a parasite extract in vitro. Our hypothesis is also supported by a significant reversal of DHFR inhibition by folate addition, which indicated a plausible mechanism of competitive inhibition. These results demonstrate that targeting filarial folate metabolism through DHFR with consequent apoptosis induction might be rewarding for therapeutic intervention. This study reveals a novel rationale of the structural analogy-based competitive inhibition of DHFR by Michael adducts of sulfonamide chalcones.
ABSTRACT
INTRODUCTION: Brain tumors cause morbidity and mortality in part through peritumoral brain edema. The current main treatment for peritumoral brain edema are corticosteroids. Due to the increased recognition of their side-effect profile, there is growing interest in finding alternatives to steroids but there is little formal study of animal models of peritumoral brain edema. This study aims to summarize the available literature. METHODS: A systematic search was undertaken of 5 literature databases (Medline, Embase, CINAHL, PubMed and the Cochrane Library). The generic strategy was to search for various terms associated with "brain tumors", "brain edema" and "animal models". RESULTS: We identified 603 reports, of which 112 were identified as relevant for full text analysis that studied 114 peritumoral brain edema animal models. We found significant heterogeneity in the species and strain of tumor-bearing animals, tumor implantation method and edema assessment. Most models did not produce appreciable brain edema and did not test for observable manifestations thereof. CONCLUSION: No animal model currently exists that enable the investigation of novel candidates for the treatment of peritumoral brain edema. With current interest in alternative treatments for peritumoral brain edema, there is an unmet need for clinically relevant animal models.