Predictors of Survival Among the Oldest Old Following Acute Hospital Admission: Insights From Clinical and Biochemical Factors.

Understanding the factors influencing survival in oldest old population is crucial for providing appropriate care and improving outcomes. This prospective observational study aimed to investigate the determinants of survival in acutely ill oldest old patients during acute hospitalization and 1-month follow-up. Various geriatric domains and biochemical markers were assessed. Among the 70 included patients with a median age of 87 (Inter quartile range: 85-90), the presence of diabetes, delirium, tachypnea, and high sirtuin-5 levels were associated with reduced in-hospital survival. Non-survivors had raised levels of Sirtuin 1 and Sirtuin 5, with an increase of 43% and 70%, respectively. At 1 month, delirium and diabetes were still associated with reduced survival. These findings suggest that type-2 diabetes, delirium, tachypnea, and high sirtuin-5 levels could serve as predictors of reduced survival in acutely ill, hospitalized oldest old patients.

Surface plasmon resonance based-optical biosensor: Emerging diagnostic tool for early detection of diseases.

The development of diagnostic tools remains at the center of the health care system. In recent times optical biosensors have been widely applied in the scientific community, especially for monitoring protein-protein or nucleic acid hybridization interactions. Optical biosensors-derived surface plasmon resonance (SPR) technology has appeared as a revolutionary technology at the current times. This review focuses on the research work in molecular biomarker evaluation using the technique based on SPR for translational clinical diagnosis. The review has covered both communicable and noncommunicable diseases by using different bio-fluids of the patient's sample for diagnosis of the diseases. An increasing number of SPR approaches have been developed in healthcare research and fundamental biological studies. The utility of SPR in the area of biosensing basically lies in its noninvasive diagnostic and prognostic feature due to its label-free high sensitivity and specificity properties. This makes SPR an invaluable tool with precise application in the recognition of different stages of the disease.

A systematic review on the available treatment modalities for Bacillus Calmette-Guérin-unresponsive carcinoma in situ and tumors in patients who are ineligible for or decline radical cystectomy.

Introduction: Globally, urothelial bladder carcinoma is a disease which carries a poor prognosis. There are various treatment modalities for urothelial bladder carcinoma with intravesical Bacillus Calmette-Guérin immunotherapy being the most efficacious intravesical therapy and the treatment of choice for patients with carcinoma in situ. A number of chemotherapeutic drugs are also available for the management of Ta/T1 tumors such as mitomycin C and epirubicin. However, relapse and progression is quite common. The optimal management of patients with Bacillus Calmette-Guérin-unresponsive disease remains to be a challenge. The purpose of this study was to conduct a systematic review on the treatment modalities available for the management of Bacillus Calmette-Guérin-unresponsive carcinoma in situ and urothelial bladder carcinoma in patients who are ineligible or decline radical cystectomy. Methods: Two authors independently searched three databases on the treatment modalities available for the management of Bacillus Calmette-Guérin-unresponsive carcinoma in situ and Bacillus Calmette-Guérin-unresponsive urothelial bladder carcinoma. Results: The systematic search resulted in 15 studies. We recommend the use of intravesical CG0070 adenovirus or hyperthermic intravesical chemotherapy mitomycin C in patients with carcinoma in situ only disease. In patients with carcinoma in situ ± Ta/T1 disease, we recommend the use of intravesical radiofrequency-induced chemohyperthermia or electromotive drug administration of mitomycin C. In patients who have Ta/T1 disease, we recommend the use of either hyperthermic intravesical chemotherapy epirubicin or electromotive drug administration mitomycin C followed by chemohyperthermia mitomycin C. If any of these second line therapies fail, an alternative regimen would be a combination of gemcitabine, cabazitaxel, and cisplatin. Conclusion: This recommendation is subject to the available resources and clinical expertise available in different hospitals. More studies using study designs such as randomized controlled trials comparing multiple drugs with larger sample sizes and regular follow-up intervals should be performed to accurately assess the different medications and aid in designing guidelines to guide the management of Bacillus Calmette-Guérin-unresponsive non-muscle invasive intravesical bladder cancer.

Evolving paradigm of thrombolysis in pulmonary embolism: Comprehensive review of clinical manifestations, indications, recent advances and guideline.

Thrombolytic therapy has been the mainstay for patients with pulmonary embolism (PE). Despite being linked to a higher risk of significant bleeding, clinical trials demonstrate that thrombolytic therapy should be used in patients with moderate to high-risk PE, in addition to hemodynamic instability symptoms. This prevents the progression of right heart failure and impending hemodynamic collapse. Diagnosing PE can be challenging due to the variety of presentations; therefore, guidelines and scoring systems have been established to guide physicians to correctly identify and manage the condition. Traditionally, systemic thrombolysis has been utilized to lyse the emboli in PE. However, newer techniques for thrombolysis have been developed, such as endovascular ultrasound-assisted catheter-directed thrombolysis for massive and intermediate-high submassive risk groups. Additional newer techniques explored are the use of extracorporeal membrane oxygenation, direct aspiration, or fragmentation with aspiration. Because of the constantly changing therapeutic options and the scarcity of randomized controlled trials, choosing the best course of treatment for a given patient may be difficult. To help, the Pulmonary Embolism Reaction Team is a multidisciplinary, rapid response team that has been developed and is used at many institutions. Hence to bridge the knowledge gap, our review highlights various indications of thrombolysis in addition to the recent advances and management guidelines.

The Role of Sirtuins in Sarcopenia and Frailty.

The population of older individuals is increasing rapidly, but only a small fraction among them is able to experiences a healthy life. Due to lack of physical exercise and oxidative stress, aging leads to sarcopenia and finally end up with frailty. Sarcopenia is a component of the frailty and described as age related degenerative changes in the skeletal muscle mass, strength and quality. Though the loss of muscle strength and mass gradually seem inevitable during aging, it can be partially prevented or overcome by a deeper insight into the pathogenesis. Sirtuin protein leads to longevity across different organisms ranging from worms to mammals. Expression of sirtuin protein increases during physical exercise and thus strengthens muscle mass. Satellite cells leads to muscle repair in a SIRT1 dependent manner. In addition, SIRT1 improves insulin sensitivity and induces autophagy in the aged mice. The current paper discussed the putative role of sirtuins in sarcopenia and frailty. Moreover, it highlighted the pathways by which sirtuins can inhibit ROS production, inflammation and mitochondrial dysfunctions and therefore confers a protective role against frailty and sarcopenia. The critical role of sirtuins in the sarcopenia and frailty pathogenesis can eventually fuel the development of novel interventions by targeting sirtuins.

Bacteremia Associated With a Toothpick Lodged in the Duodenal Wall.

Toothpick ingestion and perforation of the gastrointestinal tract, although a very rare phenomenon, carries a very high mortality risk. Most cases of toothpick ingestion remain unnoticed until very late. The symptoms are often vague, with the most common being abdominal pain. Any obscure case of abdominal pain with bacteremia must be investigated for foreign body ingestion and perforation. A CT scan is the best initial diagnostic modality for toothpick perforation but has low sensitivity with laparoscopy, and endoscopy is the preferred diagnostic tool. No single bacterium is involved in bacteremia due to toothpick ingestion. Surgical or endoscopic removal of the impacted toothpick along with prompt antibiotic therapy leads to excellent outcomes. If left untreated or in case of a late diagnosis, it may lead to life-threatening consequences. Here, we present a case of a 44-year-old man who had ingested a toothpick that pierced through and was lodged in the duodenal wall, leading to bacteremia. The patient was successfully treated and discharged.

Not Just "COVID Anxiety": A Case of Subacute Thyroiditis in a Patient Recovering From SARS-CoV-2 Infection.

Subacute thyroiditis (SAT) is an uncommon, granulomatous, inflammatory thyroid disorder. It usually presents with anterior neck and/or jaw pain, diffusely tender goiter, fever, fatigue, myalgia, and anorexia. Most patients with SAT initially develop symptoms and signs of hyperthyroidism which usually subsides within a few weeks with or without going through a transient phase of hypothyroidism. SAT is usually associated with a viral infection of the upper respiratory tract. We report a case of SAT in a 30-year-old male with a recent COVID-19 infection. The patient presented with a three days history of painful anterior neck mass and palpitations. He was diagnosed with COVID-19 16 days before presentation. His infection was mild and did not need any treatment apart from as-needed paracetamol. The patient was found to have a clinical, laboratory, and imaging findings consistent with SAT. The patient was prescribed ibuprofen, prednisone, and propranolol. The patient showed significant clinical and biochemical improvement on follow-up visits, achieving a euthyroid state within several weeks. Like many other respiratory viral illnesses, COVID-19 also seems to be associated with SAT. Other endocrinological sequelae have also been reported. While reviewing patients suffering from COVID-19 infection, these possibilities should be kept in mind.

Impact of physical activity on mitochondrial enzymes, muscle stem cell and anti-oxidant protein Sestrins in Sarcopenic mice.

INTRODUCTION: Sarcopenia is the loss of skeletal muscle mass and function. It is a major health issue in old age due to lack of understanding of the origin and molecular mechanism. Altered dietary pattern, sedentary lifestyle and physical inactivity have shown adverse effect of skeletal muscle function. Sedentary behaviour and low protein intake have been well associated with sarcopenia. Here, we aim to develop Sarcopenia mimicking murine model to observe the physiological and biochemical changes with physical activity intervention. We also intended to find the association of muscle stem cells and stress induced protein Sestrins in the developed sarcopenic model. METHODS: Male C57BL/6 mice were categorized into 4 groups: young-control (Y-Cntrl), aged-matched control (A-Cntrl), Sarcopenic-model (SAR-model) and Sarcopenic intervention group (SAR-INT) with physical exercises. SAR-model group was kept in a retrofitted confined cage for sedentary lifestyle and was fed with protein-restricted diet. Phenotypic assessment for body mass, grip strength and functional endurance was analysed to confirm the sarcopenic state. Mitochondrial enzymatic assessment, muscle stem cell (MuSCs) proliferation potential and protein quantification of Sestrins expression were performed by enzyme histochemistry, flow cytometry and surface plasmon resonance (SPR), respectively. SAR-model group was given 10 weeks physical activity intervention to assess the physiological and biochemical changes. RESULTS: Simultaneous implementation of physical inactivity by sedentary confinement and protein restricted diet led the animals to exhibit the features of sarcopenia. SAR-model group showed a decline of 8.6% (p < 0.0001) in the body weight assessment, 32% decline (p < 0.0001) in the grip strength, 28% increase in time elapsed (p < 0.0001) indicating decline in functional performance. Mitochondrial enzymes (ATPase, NADH-TR and SDH/COX) assessment exhibited low expression in SAR-model group. Ki67 positive muscle stem cell declines around 50% in the model group. SPR quantification of Sestrin 2 showed a decline of 14% which significantly improved to 28% upon physical activity intervention (p = 0.0025) in SAR-INT group. CONCLUSION: It can be summarized that the mouse model generated in the present study mimics the feature of human Sarcopenia. Physical activity intervention may improve the sarcopenic status via modulation of Sestrin 2 which can serve as potential molecule for therapeutic implication.

Serum sestrins: potential predictive molecule in human sarcopenia.

BACKGROUND: The aging trajectory from a state of robustness and good health proceeds from sarcopenia to frailty followed by disability and death due to decline in skeletal muscle mass and function. Sarcopenia is now formally recognized as a muscle disease with an ICD-10-MC diagnosis code. The autophagic response seems to be affected in the skeletal muscle during aging contributing to sarcopenia. Sestrins (Sesns) proteins play a critical role in autophagy induction under cellular stress conditions. AIMS: The study aims to identify sarcopenia in older adults using Asian Working group guidelines (AWGS) to determine clinically relevant cut-off levels for diagnosis and their association with antioxidant protein Sesns. METHODS: The study recruited 102 older adults attending Geriatric medicine OPD AIIMS, New Delhi, India. The level of serum Sesns were evaluated by Surface Plasmon Resonance (SPR) and validated by immunoblotting. Fifty older adults were diagnosed as sarcopenics according to AWGS. RESULTS: Sesn 1 (p = 0.0448) and Sesn 2 (p < 0.0001) levels were significantly reduced in sarcopenic compared to non-sarcopenic. ROC analysis showed a better cut-off of Sesn 2; 10.104 ng/µL with 92% sensitivity and 84% specificity. Even after adjusting the values with respect to confounding factors, Sesn levels remained significantly reduced in sarcopenics (p < 0.030). DISCUSSION: The level of Sesn 2 showed positive co-relation with the characteristics of sarcopenia. This study first time reported the concentration of serum sestrin in sarcopenic older adults. CONCLUSION: It can be concluded that sarcopenia can be diagnosed at the early stage by using the serum sestrin scale as one of the potential biomarker.

Postpartum Depression: Prevalence and Associated Risk Factors Among Women in Sindh, Pakistan.

Introduction Postpartum depression (PPD) is defined as the onset of depressive symptoms within six weeks of childbirth. PPD is more common in resource-constrained countries as compared to developed countries. The study aimed to evaluate the factors associated with PPD among women in Sindh, Pakistan. Methods A multi-centre, cross-sectional study was conducted at three major tertiary care setups in Sindh, Pakistan. All women presenting to the outpatient department within six weeks of giving live birth were eligible to participate. All women who had stillbirths, abortions, or were treated for a past psychiatric illness or neurological disease were excluded from the study. The Edinburgh postpartum depression scale (EPDS) was used as a screening tool. All socio-demographic factors were documented in a predefined pro forma. The data was analyzed using Statistical Package for Social Sciences (SPSS, Version 26, IBM, Chicago, IL). Results According to the Edinburgh postpartum depression scale (EPDS), the incidence of postpartum depression in the current study population was 19.3%. Of these, 12 (3.3%) women had persistently thought about self-harming. Over 100 women did not receive any formal education, constituting the majority of the study population. Formula milk feeding of the newborn was significantly associated with an increased frequency of postpartum depression (p= 0.0001). Conclusion The current study highlights the significant burden of postpartum depression in Pakistan. However, the present study failed to find any significant risk factors associated with postpartum depression. Only formula milk feeding was significantly associated with a higher frequency of PPD among study patients.

Comparative insight into nucleotide excision repair components of Plasmodium falciparum.

Nucleotide excision repair (NER) is one of the DNA repair pathways crucial for maintenance of genome integrity and deals with repair of DNA damages arising due to exogenous and endogenous factors. The multi-protein transcription initiation factor TFIIH plays a critical role in NER and transcription and is highly conserved throughout evolution. The malaria parasite Plasmodium falciparum has been a challenge for the researchers for a long time because of emergence of drug resistance. The availability of its genome sequence has opened new avenues for research. Antimalarial drugs like chloroquine and mefloquine have been reported to inhibit NER pathway mediated repair reactions and thus promote mutagenesis. Previous studies have validated existence and implied possible association of defective or altered DNA repair pathways with development of drug resistant phenotype in certain P. falciparum strains. We conjecture that a compromised NER pathway in combination with other DNA repair pathways might be conducive for the emergence and sustenance of drug resistance in P. falciparum. Therefore we decided to unravel the components of NER pathway in P. falciparum and using bioinformatics based approaches here we report a genome wide in silico analysis of NER components from P. falciparum and their comparison with the human host. Our results reveal that P. falciparum genome contains almost all the components of NER but we were unable to find clear homologue for p62 and XPC in its genome. The structure modeling of all the components further suggests that their structures are significantly conserved. Furthermore this study lays a foundation to perform similar comparative studies between drug resistant and drug sensitive strains of parasite in order to understand DNA repair-related mechanisms of drug resistance.