Permanent Disability Research Articles

Splayed Leg in Birds: Diagnosis, Therapy, and Prevention

Splayed leg is a condition where the legs are stretched outwards or sideways from their normal position under the body which is often suffered by young birds. This disorder is usually left untreated, because it is considered as a permanent disability condition that cannot be treated without examining the cause. Some of the splayed legs in chicks can be improved by treating both their legs in the correct position. Early diagnosis of splayed leg and continued appropriate therapy is needed so that the condition of the foot can be restored to normal. Incorrect diagnosis and therapy will cause the bird's feet to become permanently disabled, so the bird will suffer for the rest of its life. The diagnosis and treatment of splayed leg cases have been developed with varying results. The purpose of this review is to evaluate the diagnosis, therapy, and prevention of the occurrence of splayed legs in birds, which can be used as a reference to improve bird welfare.

Prevalence of pulmonary hypertension in chronic simple silicosis patients and its correlation with smoking history, occupation type, age and duration of silica exposure.

Silicosis is a preventable occupational health hazard with potential for permanent physical disability and increased socio-economic burden. Pulmonary hypertension (PH) secondary to chronic respiratory diseases signifies poorer prognosis and transthoracic echocardiography (TTE) has proven its usefulness as a screening tool for PH diagnosis. The objectives were to determine PH prevalence in chronic simple silicosis patients through TTE screening and correlate PH prevalence with smoking status, occupation type, age and duration of silica exposure (DSE). We enrolled 104 patients in the study based on occupational exposure to silica dust and radiologic confirmation of chronic simple silicosis. The study sample was divided into significant smokers (SS group) and insignificant smokers (InS group) on the basis of ≥10 pack years smoking history, and into drillers and dressers based on occupation type. TTE examination was performed to measure resting mean pulmonary artery pressure (mPAP) and the patients were classified into: no PH (mPAP≤20 mm Hg), borderline PH (mPAP>20 and <25 mmHg), and PH (mPAP≥25). PH prevalence was 25% in study subjects (26/104); 29.6% (16/54) among SS group versus 20% (10/50) among InS group (.52) ; and 34.2% (14/41) among drillers versus 19.1% (12/63) among dressers (p=.024). Mean age and mean duration of silica exposure among SS and InS groups were comparatively similar, while they had lower values among dressers against dressers with no statistical significance. Logistic regression analysis established a significant association of PH prevalence with higher age in the study sample, SS group and drillers group, while a significant association of PH prevalence with longer DSE was only seen in the study sample. PH prevalence was significantly associated (p=.007) with SS-driller group on comparing TTE findings with combined smoking and occupation type based groups. This study has shown PH prevalence in chronic simple silicosis patients at alarming levels, having associations with driller occupation, older age and longer DSE with varying results among groups and complex interplay with smoking exposure, suggesting the need for large sample-based molecular and genetic studies. Including TTE in the initial work-up of silicosis patients will promote timely intervention and reduce morbidity and mortality with a high benefit-cost ratio.

Modeling Survival Time to Death among Stroke Patients at Jimma University Medical Center, Southwest Ethiopia: A Retrospective Cohort Study.

Stroke is a life-threatening condition that occurs due to impaired blood flow to brain tissues. Every year, about 15 million people worldwide suffer from a stroke, with five million of them suffering from some form of permanent physical disability. Globally, stroke is the second-leading cause of death following ischemic heart disease. It is a public health burden for both developed and developing nations, including Ethiopia. This study is aimed at estimating the time to death among stroke patients at Jimma University Medical Center, Southwest Ethiopia. A facility-based retrospective cohort study was conducted among 432 patients. The data were collected from stroke patients under follow-up at Jimma University Medical Center from January 1, 2016, to January 30, 2019. A log-rank test was used to compare the survival experiences of different categories of patients. The Cox proportional hazard model and the accelerated failure time model were used to analyze the survival analysis of stroke patients using R software. An Akaike's information criterion was used to compare the fitted models. Of the 432 stroke patients followed, 223 (51.6%) experienced the event of death. The median time to death among the patients was 15 days. According to the results of the Weibull accelerated failure time model, the age of patients, atrial fibrillation, alcohol consumption, types of stroke diagnosed, hypertension, and diabetes mellitus were found to be the significant prognostic factors that contribute to shorter survival times among stroke patients. The Weibull accelerated failure time model better described the time to death of the stroke patients' data set than other distributions used in this study. Patients' age, atrial fibrillation, alcohol consumption, being diagnosed with hemorrhagic types of stroke, having hypertension, and having diabetes mellitus were found to be factors shortening survival time to death for stroke patients. Hence, healthcare professionals need to thoroughly follow the patients who pass risk factors. Moreover, patients need to be educated about lifestyle modifications.

Association between Low Bone Mineral Density and Pain in a Prospective Cohort of Adults with Sickle Cell Disease: Preliminary Results from the SCD Bone Pain Study

Background: Osteonecrosis (ON), a prevalent skeletal complication of sickle cell disease (SCD), typically associates with severe chronic pain, frequent acute care utilization, and permanent disability. We previously showed that low bone mineral density (BMD) independently associates with hip ON and chronic pain in a pediatric SCD cohort. We now present preliminary data on the association between low BMD and pain in a prospective cohort of adults enrolled in the SCD Bone Pain Study (NCT05283148). Methods: Written informed consent was obtained from all participants, who were recruited from ambulatory adults with SCD seen at the University of California Davis Comprehensive Cancer Center. All participants underwent dual-energy X-ray absorptiometry (DXA) scans of their lumbar spine, left hip, and left forearm. Vertebral fractures were assessed by thoracolumbar morphometry in the DXA scanner. All participants also completed the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) Pain Impact questionnaire. We used linear regression to evaluate the association between ASCQ-Me pain scores and low BMD (categorically defined as BMD Z-score ≤ -2 at any DXA site). We also used linear regression to determine the association between ASCQ-Me pain scores and continuous total hip and lumbar spine BMD Z-scores. Lastly, we evaluated the impact of other covariates on pain scores, with low BMD or BMD Z-scores included in the least absolute shrinkage and selection operator (LASSO, no shrinkage). Results: Thirty adults (median age 34.5 years [20-67 years]) completed the study between Nov 2022-Jul 2023. Baseline characteristics are summarized in Table 1. There was a borderline significant association between low BMD and lower (worse) pain scores (p=0.077). Continuous BMD Z-scores of the total hip (p=0.081) and lumbar spine (p=0.024) were independently associated with higher (better) pain scores. In addition to low BMD, only white blood cell count (WBC), indirect bilirubin, and vitamin D were identified as possible covariates (all had non-zero coefficients in LASSO analysis). Low BMD was significantly associated with pain (p=0.024), even after adjusting for WBC, indirect bilirubin, and vitamin D (Table 2). Similarly, we found that higher hip (p=0.059) and lumbar (p=0.027) BMD Z-scores were associated with higher (better) pain scores, despite adjusting for the same confounders. Discussion: We found low BMD in 12 of 30 (40%) adults enrolled in the SCD Bone Pain Study. Like other chronic hemolytic anemias, compensatory increased erythropoiesis leads to trabeculae degradation, cortical bone thinning, and eventual low bone mass. Lumbar vertebrae comprises mostly of trabecular bone, while the hip joint has mostly cortical bone. This might explain why mean lumbar BMD Z-scores were lower than hip BMD Z-scores (Table 1), and why lumbar spine BMD Z-scores directly and significantly correlated with pain scores (Table 2). These preliminary data suggest that pain is more prevalent in SCD adults with low BMD than those with normal BMD as we previously reported in a pediatric SCD cohort. Pain scores decrease (worsen) with increasing WBC, which suggests an inflammatory component to chronic SCD pain. Contrary to expectation, higher indirect bilirubin (a marker of increased hemolysis) significantly correlated with higher (better) pain scores. Similarly, higher vitamin D (a proxy for bone health) correlated with lower (worse) pain scores, though this association was non-significant. The reason(s) for these counterintuitive associations between pain scores, indirect bilirubin, and vitamin D levels is currently unknown. Limitations include a small sample size, though using the LASSO method for multivariate regression adjusted for this. Further, low BMD causality could not be determined at this time. Recruitment is ongoing with an enrollment target of 50 adults with SCD by Nov 2023. Analysis are ongoing to determine if SCD-modifying therapies will impact the association between low BMD and pain. Bone biomarker studies are also pending. Further, the thoracolumbar morphometry is still undergoing radiologic review, so we can further assess how vertebral compression fractures (i) correlate with pain scores, and/or (ii) attenuate the association between low BMD and pain. Identifying and treating risk factors for low BMD may alleviate bone pain and potentially improve quality of life for all people with SCD.

Neuromodulation for Post-Stroke Motor Recovery: a Narrative Review of Invasive and Non‑Invasive Tools.

Stroke remains a leading disabling condition, and many survivors have permanent disability despite acute stroke treatment and subsequent standard-of-care rehabilitation therapies. Adjunctive neuromodulation is an emerging frontier in the field of stroke recovery. In this narrative review, we aim to highlight and summarize various neuromodulation techniques currently being investigated to enhance recovery and reduce impairment in patients with stroke. For motor recovery, repetitive transcranial magnetic simulation (rTMS) and direct current stimulation (tDCS) have shown promising results in many smaller-scale trials. Still, their efficacy has yet to be proven in large-scale pivotal trials. A promising large-scale study investigating higher dose tDCS combined with constraint movement therapy to enhance motor recovery is currently underway. MRI-guided tDCS studies in subacute and chronic post-stroke aphasia showed promising benefits for picture-naming recovery. rTMS, particularly inhibitory stimulation over the contralesional homolog, could represent a pathway forward in post-stroke motor recovery in the setting of a well-designed and adequately powered clinical trial. Recently evidenced-based guideline actually supported Level A (definite efficacy) for the use of low-frequency rTMS of the primary motor cortex for hand motor recovery in the post-acute stage of stroke based on the meta-analysis result. Adjunctive vagal nerve stimulation has recently received FDA approval to enhance upper limb motor recovery in chronic ischemic stroke with moderate impairment, and progress has been made to implement it in real-world practice. Despite a few small and large-scale studies in epidural stimulation (EDS), further research on the utilization of EDS in post-stroke recovery is needed. Deep brain stimulation or stent-based neuromodulation has yet to be further tested regarding safety and efficacy. Adjunctive neuromodulation to rehabilitation therapy is a promising avenue for promoting post-stroke recovery and decreasing the overall burden of disability. The pipeline for neuromodulation technology remains strong as they span from the preclinical stage to the post-market stage. We are optimistic to see that more neuromodulation tools will be available to stroke survivors in the not-to-distant future.

Role of pathogenic and mentally pathogenic microflora, which are localized in the orotopharynx in the ethiopathogenesis of secondary osteoarthrosis

ABSTRACT. Much attention is paid to the problem of secondary osteoarthritis caused by various microorganisms and fungi of the genus S. albicans, associated with their significant growth and prevalence throughout the world among the population of various age groups, high temporary and permanent disability. At the same time, the problem of immunopathology in the pathogenesis of secondary osteoarthritis is being actively studied. The developed immunopathological process induced by pathogenic and opportunistic microflora in articular cartilage and synovial membrane is the main factor in the degenerative destruction of articular cartilage. Goal. to determine the role of pathogenic and opportunistic microflora localized in the oropharynx in the etiopathogenesis of secondary osteoarthritis. Research materials and methods. 65 patients aged from 19 to 45 years, who were undergoing inpatient treatment at Artz Klinic, Kharkiv, were examined for secondary osteoarthritis of the knee joint. The diagnosis was established according to the International Classification of Diseases of the 10th revision (ICD-10) - M18.1. Patients with a history of a high frequency of accompanying pathologies of the oropharynx were selected for the study: chronic tonsillitis - 48 (73.8%), tonsillitis - 32 (49.2%), pharyngitis - 34 (52.3%), sinusitis - 13 (20) %), otitis – 9 (13.8%) the etiology of which is determined by gram-positive and gram-negative microorganisms. All patients underwent microbiological examination of throat swabs, and 24 patients underwent microbiological examination of synovial fluid, which was taken for examination before intra-articular therapy. The obtained data were statistically processed by calculating the arithmetic mean and its error. The results. Presented modern ideas about secondary osteoarthritis caused by etiologically significant macroflora persisting in the oropharynx and as a result of organotropy due to the inclusion in its structure of mimicking antigens of articular cartilage play a leading role in the degradation of articular cartilage and articular bag, transferring the pathological process to an autoimmune basis. This approach makes it possible to develop early immunodiagnostics, prognosis of the disease, and immunocorrective therapy. Conclusions. Pathogenic and conditionally pathogenic microflora persisting in the oropharynx is characterized by organotropy (community of lipopolysaccharides and glycoproids), is identical to the cell-tissue structures of articular cartilage and synovial membrane in the causative agent and modulates the immune response through mimicking antigens.

Belantamab Mafodotin in Relapse/Refractory AL Amyloidosis- Real-Life Multi-Center Experience

Introduction: Bortezomib and daratumumab revolutionized the therapy for AL amyloidosis (AL). However, relapsed/refractory AL resistant to both drugs is an unmet clinical need, with limited options due to the frailty of these patients and paucity of prospective data. The safety profile and efficacy of belantamab mafodotin (BLM) in multiple myeloma (MM) are well known. In contrast, published data for AL are currently limited to case series of 6 (Zhang, Ann Hematol. 2022) and 12 patients only (Khwaga, Blood Cancer J. 2022). Here, we report a multicenter real-world data on 12 AL patients treated with BLM and compare these to the prior reports. Methods: We retrospectively identified all AL amyloidosis patients who received BLM outside a clinical trial, between Feb 2020-Sep 2022. The diagnosis, staging, hematologic and organ responses and progression of AL were evaluated according to consensus criteria. Event-free survival (EFS) was defined as the time from the first day of BLM administration to hematologic progression or therapy change for inadequate response or death. Results: Twelve AL patients from 5 centers in Israel and Italy were included. The median age at BLM initiation was 66 y (range 54-70). The most common FISH aberrations were 1q gain in 8 patients (67%) and t(11;14) in 5 (42%). All patients except one had cardiac involvement (92%) and 9 (75%) had renal involvement. The median number of prior lines of therapy was 3 (range 2-9). All patients previously received bortezomib, an alkylator and daratumumab, 11 (92%) received lenalidomide, 10 (83%) received pomalidomide and 9 (75%) underwent prior autologous transplant. Seven patients (58%) had Eastern cooperative oncology group performance status (ECOG-PS) of at least 2 at BLM initiation and half of the patients had AL Mayo stage of at least 3a. Most patients (10/12) received BLM as a single agent at 2.5mg/kg q3 weeks. The overall hematological response rate (ORR) to BLM was 75% (9/12), including 5 patients with complete response, 3 with very good partial response, and 1 with partial response (Figure 1). Detailed biomarker-based evaluation of organ responses was missing in many patients, yet, of 4 evaluable patients, 3 cardiac responses were observed. An additional patient had marked clinical improvement of heart failure. Four renal responses (out of 5 evaluable patients) and 2 hepatic responses (out of 2 evaluable) were also observed. With a median follow-up of 13.0 months (m) from initiation of BLM therapy (range 1.1-33.8m), the median EFS was 22.3m and the median OS was 28.8m. At data cutoff 6/12 (50%) were still on therapy, 9/12 patients (75%) were alive, all 3 deaths were due to heart disease. Seven patients (58%) had at least one grade 3 toxicity, included mostly infections/corneal toxicity. Apart from one event of grade 3 thrombocytopenia, there were no grade ≥3 hematological toxicities. No grade 4/5 toxicities were observed. Most patients (10/12, 83%) had corneal toxicity (6 patients- grade 1-2; 4 patients- grade 3), and dose reductions/delays were frequent (4/12 and 6/12, respectively). However, 7/10 patients with corneal toxicity improved overtime, no permanent visual disabilities were observed and only one patient stopped BLM due to keratopathy. Discussion: While BLM provides an ORR of 30-45% in triple-refractory MM patients, it might have a greater efficacy in AL patients. The ORR in our heavily pre-treated AL patients, as well as in other studies (2 small, retrospective + preliminary results of the EMN27 prospective study (Kastritis, EHA conference 2023) approached 60-83%, and the EFS was also encouraging. This difference may be attributed to the lower burden of disease in AL compared to MM. Alternatively, AL plasma cells may be more sensitive to BLM, in a mechanism that still merits further exploration. Corneal toxicity was similar to what was seen in MM, and overall manageable. Hematological toxicity was significantly milder than that observed in MM, probably related to the better marrow reserve in AL. Conclusions: BLM, being an off-the shelf immune therapy, with acceptable toxicity even in frail patients, can be a valuable option in AL, with a high ORR, and a signal for durable responses and high-quality organ responses in these patients.

1618. Assessing and Improving Accurate Diagnosis and Reporting of Congenital Syphilis in a Tertiary Care Children's Hospital

Abstract Background Congenital syphilis (CS) occurs due to transplacental passage of active infection to the fetus during pregnancy. Clinical presentation ranges from asymptomatic to severe permanent disability. Nationally, the incidence and prevalence of syphilis among cisgender females ages 15-44 have increased, with proportional increases in rates of CS. In 2020, 19 cases of CS were reported to the Chicago Department of Public Health (CDPH), a 138% increase from 2019 (8 cases). There are circumstances where infants with a non-reactive rapid plasma reagin (RPR-) may potentially contract syphilis in the context of inadequate maternal treatment per national guidelines. (Figure 1) Currently, only infants with RPR reactivity (RPR+) are reported to CDPH, potentially underestimating the true incidence. Our project sought to identify RPR- infants who received treatment to improve reporting to CDPH, more accurately reflect the prevalence of CS in Chicago, and ultimately guide interventions to reduce and eliminate CS.Figure 1:2021 Center for Disease Control (CDC) Possible Congenital Syphilis Definition Methods Data was collected via electronic medical record (EMR) review for infants born at Comer Children’s Hospital in Chicago, IL between 2012 and 2022, filtered using ICD-9 code (090) and ICD-10 code (A50.9) for CS. Infants were excluded if diagnosis code was used in error, there was no RPR result, or diagnosis occurred at an outside institution. (Figure 2) Infants were stratified as having CS with RPR+ or RPR-. Retrospectively, each infant was also classified with a diagnosis of less likely CS, possible CS, and proven CS per national guidelines.Figure 2:Patient Stratification by ICD-9 and ICD-10 Code for Congenital Syphilis and RPR Reactivity. RPR = Rapid Plasma Reagin Results 68 infants with CS were identified. 57 infants received IV PCN with diagnoses of proven or possible CS (84%). 51 (75%) patients were RPR+ and 17 (25%) were RPR-. (Figure 3) Of the 17 RPR-, 11 had a diagnosis of possible CS (65%) and received IV PCN while 6 (35%) had less likely CS and received one dose of intramuscular (IM) PCN (Table 1). None of the RPR- infants were reported to CDPH.Figure 3:Total Number of Congenital Syphilis Cases Based on CDC Definition. CS = Congenital Syphilis, CDC = Center for Disease ControlTable 1:Total Number of Days of Intravenous or Intramuscular Penicillin Administration per RPR reactivity.. Aq PCN = Aqueous Penicillin G, Ben PCN = Benzathine Penicillin G, IM = Intramuscular, IV = Intravenous Conclusion In this retrospective analysis, reporting CS based solely on a reactive infant RPR leads to underreporting. As we confront the rising incidence of CS, (Figure 4) it is critical that we have a complete understanding of the epidemiology which may lead to increased support for public health initiatives focused on decreasing and eliminating CS.Figure 4:Timeline of Total CS and RPR- CS Cases at Hospital per Year. CS = Congenital Syphilis Disclosures Allison H. Bartlett, MD, MS, CVS/Caremark: Honoraria Jessica Ridgway, MD, Gilead Sciences: Expert Testimony

Enhancement of mitochondrial energy metabolism by melatonin promotes vascularized skeletal muscle regeneration in a volumetric muscle loss model

Volumetric muscle loss (VML) is a condition that results in the extensive loss of 20 % or more of skeletal muscle due to trauma or tumor ablation, leading to severe functional impairment and permanent disability. The current surgical interventions have limited functional regeneration of skeletal muscle due to the compromised self-repair mechanism. Melatonin has been reported to protect skeletal muscle from exercise-induced oxidative damage and holds great potential to treat muscle diseases. In this study, we hypothesize that melatonin can enhance myoblast differentiation and promote effective recovery of skeletal muscle following VML. In vitro administration of melatonin resulted in a significant enhancement of myogenesis in C2C12 myoblast cells, as evidenced by the up-regulation of myogenic marker genes in a dose-dependent manner. Further experiments revealed that silent information of regulator type 3 (SIRT3) played a critical role in the melatonin-enhanced myoblast differentiation through enhancement of mitochondrial energy metabolism and activation of mitochondrial antioxidant enzymes such as superoxide dismutase 2 (SOD2). Silencing of Sirt3 completely abrogated the protective effect of melatonin on the mitochondrial function of myoblasts, evidenced by the increased reactive oxygen species, decreased adenosine triphosphate production, and down-regulated myoblast-specific marker gene expression. In order to attain a protracted and consistent release, liposome-encapsuled melatonin was integrated into gelatin methacryloyl hydrogel (GelMA-Lipo@MT). The implantation of GelMA-Lipo@MT into a tibialis anterior muscle defect in a VML model effectively stimulated the formation of myofibers and new blood vessels in situ, while concurrently inhibiting fibrotic collagen deposition. The findings of this study indicate that the incorporation of melatonin with GelMA hydrogel has facilitated the de novo vascularized skeletal muscle regeneration by augmenting mitochondrial energy metabolism. This represents a promising approach for the development of skeletal muscle tissue engineering, which could be utilized for the treatment of VML and other severe muscle injuries.

Disability-Adjusted Life Years Resulting from Ocular Injury among Deployed Service Members, 2001–2020

To quantify the burden of ocular injuries on deployed US service members by calculating disability-adjusted life years (DALYs). Retrospective, observational cohort study. US service members with ocular injuries sustained in combat zones from January 1, 2001 toMay 19,2020. Health states and duration of injuries were identified using data from the Defense and Veterans Eye Injury and Vision Registry. These health states were mapped to disability weights from the Global Burden of Disease (GBD) study. Average duration of injury or illness was calculated until remission or death. For the latter, life expectancy at age of sustaining injury, as identified from US Life Tablesfrom the National Vital Statistics Reports 2020, was used. Using Defense Manpower Data Center reports capturing number of service members deployed per year, incidence rates were calculated for ocular injury and DALYs. Disability-adjusted life years of ocular injury. Seventeen thousand five hundred fifty-five patients sustained ocular injury that incurred DALYs. In total, these injuries resulted in 11 214 DALYs (average, 0.64 DALYs per included patient and 20.6 DALYs per 10000 US service members per year). Severe impairment of distance vision (77.9%) and blindness (10.6%) were the primary contributors of DALYs. Although only 9.3% of patients sustained a permanent ocular injury, permanent disability accounted for 99.5% of total DALYs. The average yearly incidence rate of ocular injury was 32.0 cases per 10 000 US service members. Foreign body was the most frequent injury type (2754 occurrences), followed by abrasion (2419 occurrences) and multiple injury types (1429 occurrences). The most DALYs occurred in patients with multiple injury types (2485 DALYs), followed by abrasion (accounting for 725 DALYs) and foreign body (accounting for 461 DALYs). We report higher average DALYs per case ratio among US service members compared with the general population studied by the GBD study, highlighting the differences in probabilities of permanent injury between the two studies. Our study provides understanding of the impact of ocular injuries on active-duty service members and lays the groundwork for further research and interventions to mitigate their burden. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Piezoelectrically induced augmented functionality of primary cultured hippocampal neurons on electrospun PVDF-(Na, K) NbO3 composite fibers

Owing to the risk of permanent disability of the associated tissue/organ, peripheral nerve injuries present one of the major concerns. As growth and regeneration of axons are sensitive towards electrical activity of substrate, polyvinylidene difluoride (PVDF)−10 vol% sodium potassium niobate (NKN) piezoelectric composite fibers were electrospun and corona poled at 17 kV. Electrospun PVDF-NKN fibrous scaffolds show remarkable increase in the average number of dendrites per neuron and mean soma area of primary cultured hippocampal neurons of embryonic mice which further increases after polarization (∼ 1.3 and 1.6 times of unpoled PVDF, respectively). The developed composite can be suggested as a potential candidate for peripheral nerve regeneration.

Social determinants of mental health trajectories during midlife: a prospective British birth cohort study

BackgroundThere is an ongoing debate about whether mental wellbeing follows a U-shaped pattern across the lifespan, with a universal low point during midlife. However, existing research largely looks at average distributions of mental health problems and does not consider the underlying trajectories and social determinants. We investigate the social factors linked to changes in mental health during midlife. MethodsFor this prospective observational study, we used representative data from the 1970 British Cohort Study for the ages 34, 42, and 46–48 years (N=8581, 51·5% female, 48·5% male; born in the same week in 1970) to identify participants with declining mental health in midlife, and then used logistic regressions to determine what social factors (eg, education and employment status) were associated with this decline. Mental health was measured using the short version of the Malaise Inventory (scored 0–9). Using the cutoff point of 4 (indicating high risk of depression), we categorised participants who changed from below the cutoff to above the cutoff from age 34 to 46 years as “declining mental health” (as opposed to “stable” and “improved” mental health who were grouped together into one category). All analyses controlled for sex and parental socioeconomic status. FindingsOf the participants who responded to all mental health questions, 5302 (82·2%) remained stable, 429 (6·7%) had improved, and 671 (10·5%) had declining mental health. Our logistic regressions show that university education was linked to a lower risk of declining mental health controlled for sex and parental socioeconomic status odds ratio [OR] 0·79, 95% CI 0·85–0·94; controlling for sex and parental socioeconomic status). Experiencing unemployment during this period was linked to a higher risk of declining mental health (OR 1·75, 1·24–2·42), whereas people with permanent or temporary sickness or disability were three times more likely to experience a deterioration of mental health compared with those in full-time employment (OR 3·12, 2·46–3·93). InterpretationThe midlife decline in mental health might not be a universal phenomenon, but it might rather be influenced by social factors and changes in people's lives. Individuals experiencing unemployment, particularly those excluded from the labour market, are at a considerably higher risk of experiencing a decline in mental health. This is study provides only descriptive evidence and should be followed up by causal analyses. FundingEconomic and Social Research Council (ESRC).

Some new aspects of the pathogenesis of venous trophic ulcers

Venous trophic ulcers are one of the most common in the population, and costly in terms of treatment costs for complications of chronic venous insufficiency. The prevalence of venous trophic ulcers ranges from 0.18 to 1%. Over the age of 65 it increases to 4%. The cause of the formation of venous trophic ulcers is chronic diseases of the veins of the lower extremities. Chronic disease of the veins is a term that includes a wide range of morphological and functional disorders affecting the venous system. At the same time, even after conservative treatment, the level of recurrence of venous trophic ulcers remains extremely high, which leads to an increase in the duration of treatment for patients in the hospital, in some cases causing permanent disability in patients of working age. The literature has accumulated a huge volume of both fundamental and clinical research on the etiology, pathogenesis, diagnosis and treatment of venous ulcers. However, despite the numerous studies, the number of patients with this disease continues to steadily increase, and a number of important aspects of the pathogenesis have not yet been studied. In addition, these works do not allow us to formulate a unified concept of the pathogenesis of venous ulcers, which in turn affects the effectiveness of treatment of venous trophic ulcers. Our study highlights modern aspects of the pathogenesis of venous trophic ulcers, which may be of key importance in the treatment of this pathology. Promising directions of scientific research in this area are determined. This requires a more in-depth study of aspects of intercellular interactions, and also opens up the prospect of searching for new methods of influencing the pathogenesis of venous trophic ulcers, taking into account the presence of microflora resistant to standard antibacterial agents.

Determination of Life Microinsurance Premium Using the Commercial Rate Method

Microinsurance is insurance that is intended for people who have low incomes which is made with the aim that all levels of society can have insurance with affordable prices. Life insurance is a protection program for families in the event of unwanted things, such as death or permanent disability, to policy holders. This study aims to determine the life microinsurance premium. The data sample used is data on claim and benefit paid by life insurance company obtained from the official website of Otoritas Jasa Keuangan (OJK) Indonesia, which is assumed to have a log-normal distribution. The research method is to test the distribution of claims from the sample data using the Kolmogorov-Smirnov test. Then determine the value of the claim distribution parameter, and then calculating life microinsurance premium using the Commercial Rate method. The results obtained in the form of premium for life microinsurance that are payable by low-income people.

Systemic treatment with a selective TNFR2 agonist alters the central and peripheral immune responses and transiently improves functional outcome after experimental ischemic stroke

Ischemic stroke often leaves survivors with permanent disabilities and therapies aimed at limiting detrimental inflammation and improving functional outcome are still needed. Tumor necrosis factor (TNF) levels increase rapidly after ischemic stroke, and while signaling through TNF receptor 1 (TNFR1) is primarily detrimental, TNFR2 signaling mainly has protective functions. We therefore investigated how systemic stimulation of TNFR2 with the TNFR2 agonist NewSTAR2 affects ischemic stroke in mice. We found that NewSTAR2 treatment induced changes in peripheral immune cell numbers and transiently affected microglial numbers and neuroinflammation. However, this was not sufficient to improve long-term functional outcome after stroke in mice.

LOCAL AND SYSTEMIC MEDIATORS OF SKELETAL MUSCLE WASTING IN HUMANS FOLLOWING ACUTE TRAUMA

AbstractIntroductionSkeletal muscle wasting is an important clinical issue following acute traumatic injury, and can delay recovery and cause permanent functional disability particularly in the elderly. However, the fundamental mechanisms involved in trauma-induced muscle wasting remain poorly defined and therapeutic interventions are limited.ObjectivesTo characterise local and systemic mediators of skeletal muscle wasting in elderly patients following acute trauma.MethodsExperiments were approved by a local NHS Research Ethics Committee and all participants provided written informed consent. Vastus lateralis biopsies and serum samples were taken from human male and female patients shortly after acute trauma injury in lower limbs (n=6; mean age 78.7±4.4 y) and compared to age-matched controls (n=6; mean age 72.6±6.3 y). Atrogenes and upstream regulators (MuRF1; MAFbx; IL6, TNFα, PGC-1α) mRNA expression was assessed in muscle samples via RT-qPCR. Serum profiling of inflammatory markers (e.g. IL6, TNFα, IL1β) was further performed via multiplex assays. To determine whether systemic factors induced by trauma directly affect muscle phenotype, differentiated primary human myotubes were treated in vitro with serum from controls or trauma patients (pooled; n=3 each) in the final 24 hours of differentiation. Cells were then fixed, stained for myogenin and imaged to determine minimum ferret diameter. Statistical significance was determined at P&lt;0.05.ResultsThere was an increase in skeletal muscle mRNA expression for E3 ligase MAFbx and inflammatory cytokine IL-6 (4.6 and 21.5-fold respectively; P&lt;0.05) in trauma patients compared to controls. Expression of myogenic determination factor MyoD and regulator of mitochondrial biogenesis PGC-1α was lower in muscle of trauma patients vs controls (0.5 and 0.39-fold respectively; P&lt;0.05). In serum, trauma patients showed increased concentrations of circulating pro-inflammatory cytokines IL-6 (14.5 vs. 0.3 pg/ml; P&lt;0.05) and IL-16 (182.7 vs. 85.2 pg/ml; P&lt;0.05) compared to controls. Primary myotube experiments revealed serum from trauma patients induced atrophy (32% decrease in diameter) compared to control serum-treated cells (P&lt;0.001).ConclusionSkeletal muscle from patients following acute trauma injury showed greater expression of atrophy and inflammatory markers. Trauma patient serum exhibited higher circulating pro-inflammatory cytokine concentrations. Primary human myotubes treated with serum from trauma patients showed significant atrophy compared to healthy serum-treated controls. We speculate a mechanism(s) acting via circulating factors may contribute to skeletal muscle pathology following acute trauma.Declaration of Interest(b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Effect of Russian Current in Motor Performance among Chronic Stroke Survivors: A Pilot Study

Background and Aim: Stroke is a leading cause of permanent disability in developing nations. Motor impairment in stroke contributes to limitations in activities of daily life, participation in community, and overall quality of life. Recovery following stroke is challenged by poor lower-limb muscle performance interfering with balance, gait, and functional tasks. Objective: The objective of this study was to investigate the effect of Russian current over the quadriceps muscle in 10-m walk performance and Brunnstrom stages of lower-extremity recovery in chronic stroke survivors. Materials and Methods: The Institutional Review Board approval was obtained for this pilot study, and a total of 36 chronic stroke survivors were recruited from the outpatient department of Alva’s College of Physiotherapy and Research Center, Moodubidire, Karnataka. Consent was obtained from the voluntary participants, and they were randomly assigned to one of the two groups; intervention and the control groups. Participants in the intervention group received Russian current over the quadriceps muscle in addition to the conventional rehabilitation, whereas the control group participants received only conventional rehabilitation. The study duration was 6 weeks. The outcomes measured were 10-m walk test and Brunnstrom stages of lower-extremity recovery. Results: Statistical analysis was performed with SPSS statistical software. The Kolmogorov–Smirnov test was performed for normality. The paired t-test, within-group analysis, demonstrated a significant increase in the 10-m walk test (P &lt; 002) and Brunnstrom stage of lower extremity (P &lt; 0.043) for the intervention group. The independent t-test demonstrated a highly significant (P = 0.001) value for the intervention group than the control group. Conclusion: Statistical results conclude that Russian current is effective in improving 10-m walk performance and Brunnstrom stages of motor recovery of lower limb in chronic stroke survivors.

The circadian clock time tunes axonal regeneration

Nerve injuries cause permanent neurological disability due to limited axonal regeneration. Injury-dependent and -independent mechanisms have provided important insight into neuronal regeneration, however, common denominators underpinning regeneration remain elusive. A comparative analysis of transcriptomic datasets associated with neuronal regenerative ability revealed circadian rhythms as the most significantly enriched pathway. Subsequently, we demonstrated that sensory neurons possess an endogenous clock and that their regenerative ability displays diurnal oscillations in a murine model of sciatic nerve injury. Consistently, transcriptomic analysis showed a time-of-day-dependent enrichment for processes associated with axonal regeneration and the circadian clock. Conditional deletion experiments demonstrated that Bmal1 is required for neuronal intrinsic circadian regeneration and target re-innervation. Lastly, lithium enhanced nerve regeneration in wild-type but not in clock-deficient mice. Together, these findings demonstrate that the molecular clock fine-tunes the regenerative ability of sensory neurons and propose compounds affecting clock pathways as a novel approach to nerve repair.

Permanent disability in the criminal law: a forensic point of view

Permanent disability is a medico-judicial concept that aggravates the qualification of a criminal offence. The function of the forensic doctor is not always easy. The Algerian legislator has not defined this notion, nor determined a percentage to qualify it. From this point of view, ask yourself if such a notion is clearly defined by the legislation. On the other hand, to wonder if the determination of permanent disability constitutes a difficulty to the forensic doctor during the criminal expertise. Materials and methods: we proceeded to an analytical reading of the articles of the Algerian criminal law bearing the concept of permanent disability, In particular, article 264 and a comparison with other articles of the criminal law of different countries and the literature. A comparison with the notion of permanent disability in the civil law. A discussion of cases of victims of assault and battery observed in the forensic medicine department of the University Hospital of Sidi Bel Abbés received in the context of a criminal expertise, to determine a permanent disability. Results: the reading of the articles of the Algerian criminal law bearing the notion of permanent disability and the discussion of the cases of criminal expertises received at the forensic medicine department of the University Hospital of Sidi Bel Abbés, in order to determine a permanent disability revealed: the abstract and ambiguous character of this notion. Some of its aspects have been described, but less broadly than other countries, where this concept has not been as clearly defined.

Chronic Hepatitis B Virus Infection and Risk of Stroke Types: A Prospective Cohort Study of 500 000 Chinese Adults.

Stroke is a leading cause of mortality and permanent disability in China, with large and unexplained geographic variations in rates of different stroke types. Chronic hepatitis B virus infection is prevalent among Chinese adults and may play a role in stroke cause. The prospective China Kadoorie Biobank included >500 000 adults aged 30 to 79 years who were recruited from 10 (5 urban and 5 rural) geographically diverse areas of China from 2004 to 2008, with determination of hepatitis B surface antigen (HBsAg) positivity at baseline. During 11 years of follow-up, a total of 59 117 incident stroke cases occurred, including 11 318 intracerebral hemorrhage (ICH), 49 971 ischemic stroke, 995 subarachnoid hemorrhage, and 3036 other/unspecified stroke. Cox regression models were used to estimate adjusted hazard ratios (HRs) for risk of stroke types associated with HBsAg positivity. In a subset of 17 833 participants, liver enzymes and lipids levels were measured and compared by HBsAg status. Overall, 3.0% of participants were positive for HBsAg. HBsAg positivity was associated with an increased risk of ICH (adjusted HR, 1.29 [95% CI, 1.16-1.44]), similarly for fatal (n=5982; adjusted HR, 1.36 [95% CI, 1.16-1.59]) and nonfatal (n=5336; adjusted HR, 1.23 [95% CI, 1.06-1.44]) ICH. There were no significant associations of HBsAg positivity with risks of ischemic stroke (adjusted HR, 0.97 [95% CI, 0.92-1.03]), subarachnoid hemorrhage (adjusted HR, 0.87 [95% CI, 0.57-1.33]), or other/unspecified stroke (adjusted HR, 1.12 [95% CI, 0.89-1.42]). Compared with HBsAg-negative counterparts, HBsAg-positive individuals had lower lipid and albumin levels and higher liver enzyme levels. After adjustment for liver enzymes and albumin, the association with ICH from HBsAg positivity attenuated to 1.15 (0.90-1.48), suggesting possible mediation by abnormal liver function. Among Chinese adults, chronic hepatitis B virus infection is associated with an increased risk of ICH but not other stroke types, which may be mediated through liver dysfunction and altered lipid metabolism.