Influenza still remains one of the most challenging diseases, posing a significant threat to public health. Host lipid rafts play a critical role in influenza A virus (IAV) assembly and budding, ...however, their role in polyvalent IAV host binding and endocytosis had remained elusive until now. In the present study, we observed co-localization of IAV with a lipid raft marker ganglioside, GM1, on the host surface. Further, we isolated the lipid raft micro-domains from IAV infected cells and detected IAV protein in the raft fraction. Finally, raft disruption using Methyl-β-Cyclodextrin revealed significant reduction in IAV host binding, suggesting utilization of host rafts for polyvalent binding on the host cell surface. In addition to this, cyclodextrin mediated inhibition of raft-dependent endocytosis showed significantly reduced IAV internalization. Interestingly, exposure of cells to cyclodextrin two hours post-IAV binding showed no such reduction in IAV entry, indicating use of raft-dependent endocytosis for host entry. In summary, this study demonstrates that host lipid rafts are selected by IAV as a host attachment factors for multivalent binding, and IAV utilizes these micro-domains to exploit raft-dependent endocytosis for host internalization, a virus entry route previously unknown for IAV.
Time-restricted meal intake (TRM) has shown potential benefits such as enhanced insulin sensitivity, lowered blood sugar levels, and possible weight loss in individuals with type 2 diabetes mellitus ...(T2DM). Our study aimed to investigate the impact of TRM on lipid profile parameters such as total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) in fasting conditions in T2DM patients.
In total, 400 patients from the endocrinology department at King George's Medical University (KGMU), Lucknow were enrolled in this study, adhering to the guidelines of the American Diabetes Association (ADA). Male and female patients with recently diagnosed T2DM (in the past five years), aged between 25 to 60 years, on oral anti-diabetic therapy excluding insulin, expressing willingness to provide written consent and to adhere to TRM were included in the TRM group. It was a longitudinal study as diabetic dyslipidemia is primarily caused by insulin resistance and nutritional reasons and we wanted to assess the effect of TRM on lipid profile in T2DM patients. Patients were enrolled via simple random sampling using the random number table method (computerized). The TRM group had an early dinner at 7 pm whereas the control group was of non-TRM/late-night eaters. TRM group was given comprehensive guidance including strategies to manage hunger, permissible beverage options (water and prescribed medication) during the fasting period, and daily maintenance of a diary documenting their timing, type, and quantity of food intake which they were requested to bring fortnightly. Emphasis was placed on recording even minor dietary items consumed throughout the day. The TRM group consumed food ad libitum during a 12-hour eating window from breakfast at 7 am to dinner at 7 pm. Data distribution was non-parametric. Mann-Whitney U test compared TRM and control group using mean values at baseline and follow-ups. Analysis used GraphPad Prism 9.2.0 software (GraphPad Inc., La Jolla, CA). A p-value less than 0.05 (p < 0.05) was considered statistically significant.
A total of 127 patients were lost to follow-up, resulting in 273 patients who completed the study. The mean value of TC in the TRM and non-TRM groups using the Mann-Whitney U test registered a highly significant p-value <0.0001 at 18 months, with a decrease of 14.17% from baseline in the TRM group and a decrease of 1.53% from baseline in the non-TRM group. The TRM group had a decrease of 24.75% in TG from a baseline value of 145.4±41.9, whereas the non-TRM group showed a decrease of 2.2% from a baseline value of 154.7±37.30 (p-value <0.0001). The TRM group showed an increase of 9.25% in HDL from a baseline value of 50.14±8.58; the non-TRM group showed an increase of 0.82% from a baseline value of 48.62±9.31 (p-value <0.0001). TRM group showed a decrease of 8.62% in LDL from a baseline value of 68.20±16.2 while the non-TRM group showed an increase of 1.54% from a baseline value of 65.38±19.3 (p-value <0.0002). The TRM group showed a decrease of 13.97% in VLDL from a baseline value of 32.20±18.7; the non-TRM group showed an increase of 4% from a baseline value of 30.16±24.2 (p-value <0.0001).
Our study's promising results underscore the potential of TRM as an effective strategy for managing dyslipidemia in individuals with T2DM, even over prolonged periods.
This study aimed to investigate the impact of time-restricted meal intake (TRM) on anthropometric and biochemical parameters in patients with type 2 diabetes mellitus (T2DM).
A total of 400 patients ...diagnosed with T2DM were selected from the Endocrinology Department at King George's Medical University (KGMU), Lucknow, based on the American Diabetes Association (ADA) guidelines and specific criteria. A total of 127 patients were lost to follow-up, resulting in 273 patients who completed the study. The patients were randomly assigned to two groups: the TRM group (consenting to have an early dinner at 7 pm) and the control group (non-TRM/late-night eater group). Baseline data were recorded, and follow-up assessments were conducted at six months, 12 months, and 18 months. Informed consent was obtained, and a diet chart was regularly maintained and updated.
The TRM group experienced a significant weight loss of 3.88 kg (5.45%) and a substantial reduction in BMI by 1.5 units (5.26%). In contrast, the non-TRM/control group had smaller reductions in weight (1.36 kg, 1.77%) and BMI (0.5 units, 1.65%). TRM group showed significant reductions in fasting blood sugar levels by 33.9 mg/dl (21.17%), postprandial blood sugar levels by 94.6 mg/dl (38.88%), and glycosylated hemoglobin (HbA1c) levels by 1.37 (15.87%). These improvements were significantly greater than the reductions observed in the control group, which had decreases of 29.3 mg/dl (17.85%) in fasting blood sugar levels, 41.6 mg/dl (16.84%) in postprandial blood sugar levels, and 0.59 (6.89%) in HbA1c levels.
Our findings underscore the potential of TRM as an effective strategy for weight management and glycemic control in patients with T2DM, even in a long-term context. These results support time-restricted eating as a sustainable lifestyle modification for managing chronic metabolic diseases.
Chikungunya fever (CHIKF) is an arbovirus disease caused by chikungunya virus (CHIKV), an alphavirus of Togaviridae family. Transmission follows a human-mosquito-human cycle starting with a mosquito ...bite. Subsequently, symptoms develop after 2–6 days of incubation, including high fever and severe arthralgia. The disease is self-limiting and usually resolve within 2 weeks. However, chronic disease can last up to several years with persistent polyarthralgia. Overlapping symptoms and common vector with dengue and malaria present many challenges for diagnosis and treatment of this disease. CHIKF was reported in India in 1963 for the first time. After a period of quiescence lasting up to 32 years, CHIKV re-emerged in India in 2005. Currently, every part of the country has become endemic for the disease with outbreaks resulting in huge economic and productivity losses. Several mutations have been identified in circulating strains of the virus resulting in better adaptations or increased fitness in the vector(s), effective transmission, and disease severity. CHIKV evolution has been a significant driver of epidemics in India, hence, the need to focus on proper surveillance, and implementation of prevention and control measure in the country. Presently, there are no licensed vaccines or antivirals available; however, India has initiated several efforts in this direction including traditional medicines. In this review, we present the current status of CHIKF in India.
The major arboviruses mainly belong to the
,
, and
families, among which the chikungunya virus and dengue virus have emerged as global public health problems. The main objective of this study was to ...develop specific, sensitive, and cost-effective molecular multiplex RT-PCR and RT-qPCR assays for the rapid and simultaneous detection of CHIKV and the four serotypes of DENV for arbovirus surveillance. Specific primers for all viruses were designed, and one-step multiplex RT-PCR (mRT-PCR) and RT-qPCR (mRT-qPCR) were developed using reference strains of the CHIKV and DENV serotypes. The specificity of the test for all the viruses was confirmed through sequencing. The standard curves showed a high correlation coefficient, R
= 0.99, for DENV-2 and DENV-3; R
= 0.98, for DENV-4; and CHIKV; R
= 0.93, for DENV-1. The limits of detection were calculated to be 4.1 × 10
copies/reaction for DENV-1, DENV-3, and CHIKV and 4.1 × 10
for DENV-2 and DENV-4. The specificity and sensitivity of the newly developed mRT-PCR and mRT-qPCR were validated using positive serum samples collected from India and Burkina Faso. The sensitivity of mRT-PCR and mRT-qPCR are 91%, and 100%, respectively. The specificity of both assays was 100%. mRT-PCR and mRT-qPCR assays are low-cost, and a combination of both will be a useful tool for arbovirus surveillance.
To establish a productive infection in host cells, viruses often use one or multiple host membrane glycoproteins as their receptors. For Influenza A virus (IAV) such a glycoprotein receptor has not ...been described, to date. Here we show that IAV is using the host membrane glycoprotein CD66c as a receptor for entry into human epithelial lung cells. Neuraminidase (NA), a viral spike protein, binds to CD66c on the cell surface during IAV entry into the host cells. Lung cells overexpressing CD66c showed an increase in virus binding and subsequent entry into the cell. Upon comparison, CD66c demonstrated higher binding capacity than other membrane glycoproteins (EGFR and DC-SIGN) reported earlier to facilitate IAV entry into host cells. siRNA mediated knockdown of CD66c from lung cells inhibited virus binding on cell surface and entry into cells. Blocking CD66c by antibody on the cell surface resulted in decreased virus entry. We found that CD66c is a specific glycoprotein receptor for influenza A virus that did not affect entry of non-IAV RNA virus (Hepatitis C virus). Finally, IAV pre-incubated with recombinant CD66c protein when administered intranasally in mice showed decreased cytopathic effects in mice lungs. This publication is the first to report CD66c (Carcinoembryonic cell adhesion molecule 6 or CEACAM6) as a glycoprotein receptor for Influenza A virus.
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that was first identified in December 2019, in Wuhan, China was found to be the etiological agent for a novel respiratory infection ...that led to a Coronavirus Induced Disease named COVID-19. The disease spread to pandemic magnitudes within a few weeks and since then we have been dealing with several waves across the world, due to the emergence of variants and novel mutations in this RNA virus. A direct outcome of these variants apart from the spike of cases is the diverse disease presentation and difficulty in employing effective diagnostic tools apart from confusing disease outcomes. Transmissibility rates of the variants, host response, and virus evolution are some of the features found to impact COVID-19 disease management. In this review, we will discuss the emerging variants of SARS-CoV-2, notable mutations in the viral genome, the possible impact of these mutations on detection, disease presentation, and management as well as the recent findings in the mechanisms that underlie virus-host interaction. Our aim is to invigorate a scientific debate on how pathogenic potential of the new pandemic viral strains contributes toward development in the field of virology in general and COVID-19 disease in particular.
The change in body position can alter pulmonary functions parameters, therefore it is important to understand the physiological basis of these alteration. Ideally, spirometry is done in sitting ...position until the subject is unable to do so. Hospitalized patients often assume recumbent body positions irrespective of underlying pathology. Hence, need arises to find out best recumbent body positions for the benefit of these patients to make breathing comfortable for them.
The aim of this study was to find out whether the change from the supine position to crook lying and Fowler's position (45° dorsal elevation) causes change in spirometric parameters.
The present work was carried out at Department of Physiology, King George's Medical University, Lucknow. A total 131 apparently healthy individuals were enrolled in this cross-sectional study. Lung function was assessed using a PC-based spirometer according to American Thoracic Society guideline in the supine, crook lying and Fowler's position (45° dorsal elevation).
The study consisted of 131 subjects (male 66%, female 34%), with mean age of 20.15±2.71 years and BMI 21.20±3.28 Kg/m
. Repeated measures ANOVA with post hoc Bonferroni test was used to compare the mean values between each body position. Compared with the other two positions, Fowler's position showed significantly (p<0.05) higher values for FVC, FEV
, PEF, FEF
.
Recumbent body position influences spirometric parameters in young healthy subjects. We demonstrated that spirometric values are higher in the Fowler's position than in the supine or crook lying position. The results of this study will help in the selection of the best alternative position for the spirometry in bed ridden patients.
Background:
Absconding from psychiatric hospitals is of great concern for patients and caregivers. Absconding affects not only the treatment and safety of these patients but also patient’s caregivers ...and the community. Further investigation is needed to examine the pattern of this event and the characteristics of patients who abscond. Hence, our study was aimed to examine the sociodemographic and clinical profiles of inpatients who absconded from a psychiatric hospital in five years and to compare them with matched controls.
Methods:
A retrospective chart review of inpatients who absconded and matched control inpatients during the specified period of five years from January 2014 to December 2018 was done at a psychiatric hospital. Each control was matched with a corresponding absconding case on the following order: (a) admission ward, (b) admission period, (c) diagnosis, and (d) age. Results: Among 20,052 adult admissions during the specified period, 38 patients absconded, with a rate of 1.8 per 1,000 admissions. Most of them were male, from a younger age group, diagnosed with schizophrenia or mood disorder, and having comorbid substance use disorder, irritable affect, impaired judgment, and absent insight. Most of the events occurred within the first two weeks of admission. About 11% of them had a history of prior absconding from the hospital.
Conclusion:
Knowledge about the associated sociodemographic and clinical profile would help clinicians and mental health care professionals to prevent absconding. Further risk assessment using a patient’s profile would help to reduce absconding events from psychiatric hospitals in the future.
Several Single Nucleotide Polymorphisms (SNPs) in lipid transport genes have been shown to be associated with Coronary Artery Disease (CAD). The Hepatic Lipase (HL)glycoprotein is a key component ...that catalyzes the hydrolysis of triglycerides and phospholipids in all major classes of lipoproteins.
We studied whether the HL gene-250G/A polymorphism affect blood lipid level and the CAD in a North Indian population.
A total number of 477 subjects were enrolled in the study after approval of the Institutional Ethics Committee. Out of 477 subjects, 233 were with coronary artery disease as study group and 244 subjects without coronary artery disease as control group. All subjects recruited with matched ethnicity in age group of 40-70 years. Blood samples were collected in EDTA vials and genomic DNA was extracted from blood using the phenol-chloroform method. Lipid profile was estimated by using a commercially available kit. Polymorphisms in the HL (-250 G/A) gene were analysed by using restriction fragment length polymorphism-polymerase chain reaction (PCR-RFLP) method. The effect of this polymorphism on plasma lipids, lipoproteins and coronary artery disease was determined.
In Human Hepatic Lipase (LIPC)-250G/A genotype, the frequencies of GG, GA and AA genotype in CAD group was 80.69%, 15.45% and 3.86%, respectively; in the control group, the corresponding frequencies were 90.16%, 9.02% and 0.82%, respectively. A significant difference was found in the genotype (LIPC-250G/A) distribution between the two groups. Further logistic regression analysis indicated that the GA and AA genotypes in SNP-250G/A were significantly associated with CAD in all genetic models (In codominant model- GA vs. GG, OR=1.91, 95% CI=1. 09-3.37, p=0. 03 and AA vs. GG, OR= 5.26, 95% CI= 1.10-24.60, p=0.04; in dominant model- GA+AA vs. GG, OR=2.19, p=0.004 and in recessive model- AA vs. GG+GA, OR=5.26, p=0.04 whereas, A allele at nucleotide -250G/A in the LIPC gene had an association with increased risk of CAD (OR=2.33, p=<0.008).
Our findings indicated that the higher frequency of a dominant model (GA+AA) as well as mutant allele A of LIPC-250 G/A polymorphism is significantly associated with risk of CAD and the lipid profile can be used as a predictor of CAD.
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