Prevalence and patterns of post-COVID-19 symptoms in recovered patients of Delhi, India: a population-based study.

BACKGROUND: Post-coronavirus disease 2019 (COVID-19) symptoms were widely reported. However, data on post-COVID-19 conditions following infection with the Omicron variant remained scarce. This prospective study was conducted to understand the prevalence, patterns, and duration of symptoms in patients who had recovered from COVID-19. METHODS: A prospective study was conducted across 11 districts of Delhi, India, among individuals who had recovered from COVID-19. Study participants were enrolled, and then returned for post-recovery follow-up at 3 months and 6 months interval. RESULTS: The mean age of study participants was 42.07 years, with a standard deviation of 14.89 years. The majority of the participants (79.7%) reported experiencing post-COVID-19 symptoms. The most common symptoms included joint pain (36.0%), persistent dry cough (35.7%), anxiety (28.4%), and shortness of breath (27.1%). Other symptoms were persistent fatigue (21.6%), persistent headache (20.0%), forgetfulness (19.7%), and limb weakness (18.6%). The longest duration of symptom was observed to be anxiety (138.75±54.14 days), followed by fatigue (137.57±48.33 days), shortness of breath (131.89±60.21 days), and joint pain/swelling (131.59±58.76 days). At the first follow-up visit, 2.2% of participants presented with abnormal electrocardiogram readings, but no abnormalities were noticed during the second follow-up. Additionally, 4.06% of participants exhibited abnormal chest X-ray findings at the first followup, which decreased to 2.16% by the second visit. CONCLUSION: The most frequently reported post-COVID-19 symptoms were joint pain, dry cough, anxiety and shortness of breath. These clinical symptoms persisted for up to 6 months, with evidence of multi-system involvement. Consequently, findings highlighted the need for long-term follow-up during the post-COVID-19 period.

Case Report: Secondary Hemophagocytic Lymphohistiocytosis (sHLH) and Candida auris Fungemia in Post-acute COVID-19 Syndrome: A Clinical Challenge.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a disease (COVID-19) with multisystem involvement. The world is now entering a phase of post-COVID-19 manifestations in this pandemic. Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening hyperinflammatory event triggered by viral infections, including SARS-CoV-2. Both Multisystem Inflammatory Syndrome-Adults (MIS-A) and Cytokine Storm Syndrome (CSS) are considered close differentials of sHLH and add to the spectrum of Post-acute COVID-19 syndrome (PACS). In this report, we presented the case of a middle-aged Asian man who was initially discharged upon recovery from severe COVID-19 infection after 17 days of hospitalization to a private institute and later came to our hospital 13 days post-discharge. Here, he was diagnosed with sHLH, occurring as an extension of CSS, with delayed presentation falling within the spectrum of PACS. The diagnosis of sHLH was made holistically with the HLH-2004 criteria. Our patient initially responded to intravenous immunoglobulin (IVIG) and dexamethasone, later complicated by disseminated Candida auris infection and had a fatal outcome. Though many cases of HLH during active COVID-19 and a few cases post COVID-19 recovery have been reported, based on H-score, which has limitations as a diagnostic tool. We report the first case report of post-COVID-19 sHLH using the HLH-2004 criteria, complicated by disseminated Candidemia, emphasizing that the care of patients with COVID-19 does not conclude at the time of hospital discharge. We highlight the importance of surveillance in the post-COVID phase for early detection of sHLH which may predispose to fatal opportunistic infections (OIs).

Effect Compartment Model for the Evaluation of Tolerance to Psychological Highness Following Smoking Marijuana.

The purpose of this study is to evaluate the development of tolerance, using a population modeling approach, in recreational marijuana users after acute pulmonary administration of tetrahydrocannabinol (THC), a primary ingredient in marijuana. A total of 85 subjects in 3 separate studies smoked marijuana cigarettes (dose = 13-49 mg) under controlled conditions. Each study was designed as a randomized, crossover, double-blind, and placebo-controlled study. Up to 5 THC plasma samples and corresponding user-reported psychological highness were pooled for population modeling analyses. Age, sex, user status, and body mass index were evaluated as covariates. Population pharmacokinetic (PK) parameters were estimated in the 2-compartment PK model. PK parameters were fixed in the effect compartment model to describe the relationship between THC plasma concentration-psychological highness. The distribution rate constant in the effect compartment was estimated to be 0.988 (95%CI 0.964-1.010)/h. The population mean half-maximal effective concentration (EC50 ) was 23.8 (95%CI 22.7-24.9) ng/mL. Covariate analysis revealed that user status was a significant covariate, and that chronic users appear to need higher plasma concentrations compared with occasional users to achieve a similar degree of highness. The modeling results conclude that chronic users develop tolerance to euphoria, which is the primary central nervous system effect of smoking marijuana.

Current Perspectives of Healthy Mitochondrial Function for Healthy Neurons.

The neuron is high-energy utilizing tissue. The rate of neuronal cell respiration is higher than in other cells. Cellular respiration occurs with mitochondria. The healthy production and functions of mitochondria play a key role in the maintenance of healthy neurons. In pathological conditions such as neurodegenerative diseases, healthy mitochondria help to alleviate pathological events in neuronal cells. Conversely, mitochondrial dysfunction promotes the acceleration of the neurodegenerative process. Furthermore, glial-derived mitochondria contribute to multiple roles in the regulation of healthy neuron functions. It also supports releasing of the neurotransmitters; generation of the impulses, regulation of the membrane potential and molecular dynamics; controlling of the axonal transport; controlling of the mitochondrial fission and fusion functions in the peripheral as well as the central nervous system. Moreover, it plays a key role in the regeneration process of neuronal cells. Therefore, healthy mitochondria can provide a healthy environment for neuronal cell function and can treat neurodegenerative disorders. In this review, we explore the current view of healthy mitochondria and their role in healthy neuronal functions.

Therapeutic applications of transdermal microneedles.

Transdermal drug-delivery systems (TDDS) offer an attractive alternative to the oral route for delivery of biotherapeutics. Technological advancements in the past few decades have revolutionized the fabrication of micro-structured devices including creation of microneedles (MC). These devices are used for delivering peptides, macromolecules such as proteins and DNA, and other therapeutics through the skin. Here, we review the current use of MCs as a cost effective method for the self-administration of therapeutics. We will then review the current and common use of MCs as an effective treatment strategy for a broad range of diseases and their utility in the generation of effective vaccination delivery platforms. Finally, we will summarize the currently FDA approved MCs and their applications, along with the ongoing clinical trials that use such devices.

Prevalence of Autonomic Neuropathy in Patients of Rheumatoid Arthritis and Its Correlation with Disease Severity.

INTRODUCTION: Autonomic Neuropathy (AN), found to be a strong predictor of sudden cardiac death, has been reported variably in patients with Rheumatoid Arthritis (RA). Manifesting as sweating disturbances, gastrointestinal irregularities, bladder or erectile dysfunction, AN can significantly affect a patient's quality of life and alter the course of the disease. AIM: This study was undertaken to find out the prevalence and severity of AN in RA patients attending the Rheumatology Clinic at a Tertiary Care Hospital in New Delhi, India and also to investigate its correlation with patient and disease factors such as age, gender, disease severity, duration and serological status. MATERIALS AND METHODS: In this cross-sectional study, AN was assessed subjectively by a survey of autonomic symptoms. Cardiac autonomic involvement was assessed by five cardiovascular reflex tests as described by Ewing: Heart Rate (HR) response to deep breathing, standing, and Valsalva and Blood Pressure (BP) response to standing and sustained handgrip. RESULTS: A total of 31 RA patients and 31 age and sex matched healthy volunteers were recruited. Upon analysis it was found that the prevalence of cardiac AN was significantly higher in patients (80.65%) as compared to controls (51.61%) (p=0.016). Positive correlation with disease severity was observed with the patient reported questionnaire but not with the objective cardiovascular reflex tests. No significant correlation between grade of AN and patient's age, gender, disease duration or serological status was established. CONCLUSION: At the end of the study, it was concluded that the pathological mechanisms responsible for autonomic dysfunction are more active in RA as compared to others.

Combined Arterial and Venous Thrombosis in Ulcerative Colitis- A Rare Vascular Manifestation.

Combined arterial and venous thrombosis in patients with ulcerative colitis is a rare extra vascular manifestation, which motivated the current report. Increased coagulability is a recognised feature of ulcerative colitis with frequency increasing during flares. We report the case of a 42-year-old lady who was a diagnosed case of ulcerative colitis, currently in remission. She presented with swelling followed by discolouration of left lower limb which later was diagnosed as deep venous thrombosis combined with femoral and popliteal artery thrombosis. This led to wet gangrene of the limb, sepsis, septic shock and death despite aggressive management with heparin infusion, ionotropes, and parenteral antibiotics therapy.

Pheochromocytoma and tetralogy of Fallot: Coincidence or a rare association?

We report the case of a 25-year-old woman with tetralogy of Fallot who presented with chest pain and hypertension, and on further investigation, was diagnosed with a pheochromocytoma in the right adrenal gland. She underwent surgical excision of the tumor. While the simultaneous occurrence of these two diseases is extremely rare, the suspicion of a possible relationship has been raised in the past.

Current and emerging lipid-based systems for transdermal drug delivery.

Developing a transdermal drug delivery system is a challenging task considering the selective permeability of the skin and the physicochemical properties the drug must possess to permeate through the skin. Lipid-based drug delivery systems have contributed a great deal in this direction in the last few decades, and thereby have helped to expand the range of therapeutic molecules that can be delivered through the skin in a safe and effective manner. Additionally, vesicular delivery systems such as nanoparticles and emulsions have also played important roles in providing alternative novel approaches for drug delivery. In this article, we will discuss some of the current and future lipid-based systems for transdermal drug delivery along with the associated challenges.

Exploring the potential of flunarizine for Cisplatin-induced painful uremic neuropathy in rats.

PURPOSE: The present study was designed to explore the potential of flunarizine for cisplatin induced painful uremic neuropathy in rats. METHODS: Cisplatin (2 mg/kg; i.p., for 5 consecutive days) was administered and renal uremic markers i.e., serum creatinine were estimated on days 4 and 25. Behavioral changes were assessed in terms of thermal hyperalgesia (hot plate, plantar, tail immersion, and tail flick tests at different time intervals). Biochemical analysis of total calcium, superoxide anion, DNA, and transketolase, and myeloperoxidase activity in tissue samples was also performed. Furthermore, flunarizine (100, 200, and 300 µM/kg; p.o., for 21 consecutive days) was administered to evaluate its potency on uremic neuropathy, and the results were compared with those for the carbamazepine-treated (30 mg/kg; p.o., for 21 consecutive days) groups. RESULTS: Flunarizine attenuated the cisplatin-induced uremic neuropathy, and the degree of behavioral and biochemical changes in serum and tissue samples in a dose dependent manner. The medium and high doses of flunarizine were shown to produce a significant effect on cisplatin induced painful uremic neuropathy. CONCLUSIONS: Our results indicate the potential of flunarizine for anti-oxidative, anti-inflammatory, and neuroprotective actions. Therefore, it may have use as a novel therapeutic agent for the management of painful uremic neuropathy.

Prevalence of non-alcoholic fatty liver disease and its correlation with coronary risk factors in patients with type 2 diabetes.

OBJECTIVES: To estimate the prevalence of non-alcoholic fatty liver disease (NAFLD) by ultrasonography, and to correlate NAFLD with coronary artery disease (CAD) and coronary risk factors in a group of Indian type 2 diabetics. METHODS: Consecutive patients of type 2 diabetes were recruited. History and physical examination were recorded. Laboratory investigations included fasting and 2-hour post-prandial blood glucose, blood urea, serum creatinine, liver function tests, lipid profile, glycated haemoglobin, microalbuminuria, and ultrasonographic measurement of carotid intimal-medial thickness (CIMT). NAFLD was diagnosed on the basis of ultrasound assessment of the liver. RESULTS: The study group (n=124) was divided into a NAFLD group (n=71) and a non-NAFLD group (n=53). The prevalence of NAFLD was 57.2%. CAD was more prevalent in the NAFLD subgroup (60.5%) compared to the non-NAFLD subgroup (45.2%). The NAFLD subgroup had higher prevalence of hypertension, smoking, obesity (measured by BMI), central obesity (measured by waist circumference and waist hip ratio), higher HbAlc, higher triglyceride levels and lower HDL levels, and higher mean CIMT. Using binary logistic regression analysis, it was found that hypertension (p=0.013), LDL cholesterol (p=0.049), microalbuminuria (p=0.034) and NAFLD (p=0.016) were significantly correlated with CAD. CONCLUSION: Among type 2 diabetics, NAFLD clusters with traditional coronary risk factors. It is a surrogate and fairly reliable marker of risk for CAD amongst type 2 diabetic patients. Ultrasonographically detected NAFLD is a simple, cheap, and safely assessable parameter for coronary risk stratification in type 2 diabetics.

Reno-protective role of flunarizine (mitochondrial permeability transition pore inactivator) against gentamicin induced nephrotoxicity in rats.

This study was aimed to evaluate the role of flunarizine on gentamicin (GEM) induced nephrotoxicity in rat. Administration of GEM (40 mg/kg, s.c. for 10 consecutive days) significantly increased blood urea nitrogen (BUN), N-acetyl ß-d-glucosaminidase (NAG), thiobarbituric acid reactive substances (TBARS) and total calcium whereas, decreased body weight, fractional excretion of sodium (FrNa), creatinine clearance (CrCl), reduced glutathione (GSH), mitochondrial cytochrome c oxidase (Cyt-C oxidase) and ATP levels resulting in nephrotoxicity. Further, flunarizine (100, 200 and 300 µmol/kg, p.o.) was administered to evaluate its renoprotective effect against GEM induced nephrotoxicity and the results were compared with cylcosporin A (CsA, 50 µmol/kg, p.o.). Flunarizine resulted in the attenuation of renal dysfunction and oxidative marker changes in rats subjected to GEM induced nephrotoxicity in a dose dependent manner. Medium and higher doses of flunarizine produced significant renal protective effect which was comparable to cyclosporin A. The results of this study clearly revealed that flunarizine protected the kidney against the nephrotoxic effect of GEM via mitochondrial permeability transition pore (MPTP) inactivation potential.

The antiinflammatory potential of phenolic compounds from Emblica officinalis L. in rat.

Antiinflammatory effects of phenolic compounds from Emblica officinalis were evaluated in carrageenan and cotton pellet induced acute and chronic inflammatory animal model. Fractions of E. officinalis containing free (FPEO) and bounded (BPEO) phenolic compounds were assessed by HPLC technique. The free and bound phenolic compounds were studied for their acute and chronic antiinflammatory activity at dose level of 20 and 40 mg/kg. The carrageenan induced acute inflammation was assessed by measuring rat paw volume at different time of intervals. Further, cotton pellet induced chronic inflammation was assessed by granulomatous tissue mass estimation along with the estimation of tissue biomarker changes (i.e. lipid peroxidation, reduced glutathione, myeloperoxidase and plasma extravasation). The results indicated that in both acute and chronic inflammation, FPEO and BPEO show reduction in the inflammation, but significant effects was observed only at high doses of both fractions which was comparable to diclofenac treated group. In conclusion, phenolic compounds of E. officinalis may serve as potential herbal candidate for amelioration of acute and chronic inflammation due to their modulatory action of free radicals.

Ameliorative effect of flunarizine in cisplatin-induced acute renal failure via mitochondrial permeability transition pore inactivation in rats.

This study was aimed to evaluate the protective effect of flunarizine on cisplatin-induced acute renal failure. Administration of cisplatin (6 mg/kg, i.p. on day 6) significantly increased serum blood urea nitrogen and creatinine, urinary N-acetyl ß-D-glucosaminidase, tissue thiobarbituric acid reactive substances and total calcium whereas, decreased body weight, fractional excretion of sodium, creatinine clearance tissue-reduced glutathione, mitochondrial cytochrome c oxidase, and ATP levels were observed in acute renal failure rats. Moreover, cisplatin produced histopathological changes in the renal tissue. Furthermore, flunarizine (100, 200, and 300 µM/kg, p.o., for six consecutive days) was administered to evaluate its therapeutic potential in acute renal failure, and the results were compared with cyclosporin A (50 µM/kg, p.o., for six consecutive days) as a reference drug. Flunarizine resulted in the attenuation of cisplatin-induced renal dysfunction, oxidative stress marker, mitochondrial damage, and histopathological changes in rats. Medium and higher doses of flunarizine produced significant renal protective effect which was comparable to cyclosporin A. The results of this study clearly revealed that flunarizine protected the kidney against the nephrotoxic effect of cisplatin via mitochondrial permeability transition pore inactivation potential.