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1.
Cureus ; 16(4): e58105, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38738075

ABSTRACT

INTRODUCTION: The pervasive impact of alcohol use disorder (AUD) within families, particularly on parenting roles in Kerala, India, necessitates an in-depth exploration. This study aims to uncover the unique challenges and coping strategies employed by wives of individuals with AUD against a backdrop of societal stigma and economic hardship. METHODOLOGY: This study, employing a qualitative narrative research design, delves into the experiences of 30 wives of men with AUD in Kerala. The study delves into the complexities of navigating parenting responsibilities amid challenges related to AUD, employing in-depth interviews with the aid of a semi-structured interview guide conducted in Malayalam.​​​​​ The researchers used narrative analysis to extract the themes related to coping mechanisms, resilience, and the impact on children's psychological health. RESULTS: The study highlights significant emotional and social burdens on wives, including solo parenting, financial strain, and social stigma. Despite these challenges, the resilience and adaptive strategies of these women stand out, with extended family support, community resources, and personal beliefs playing crucial roles in their coping mechanisms. The study points out variations in coping strategies across different socio-economic and educational backgrounds. IMPLICATIONS: The findings underscore the necessity for comprehensive support systems sensitive to the socio-demographic differences among families affected by AUD. Tailored interventions that enhance access to professional support, foster community solidarity, and provide economic assistance are critical. Moreover, efforts to reduce stigma and promote understanding are essential for improving the psychological health and overall quality of life of these families.

2.
Cureus ; 16(4): e57461, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38699092

ABSTRACT

The issue of alcohol use disorder (AUD) has received significant attention, with a primary focus on individuals directly afflicted by the disorder. This extensive focus, while necessary, often overlooks the profound impact that AUD has on the family unit, particularly on spouses who play a crucial role in the dynamics of coping and recovery. However, the psychosocial and emotional challenges encountered by wives of those with AUD have been largely neglected in both research and therapeutic interventions. This oversight not only minimizes their suffering but also overlooks their potential contribution to the recovery process, underscoring the need for a more inclusive approach to understanding and addressing AUD. Building upon this foundation, the current study delves into the less explored terrain of the psychosocial and emotional ramifications borne by wives of individuals suffering from AUD. By highlighting the pivotal role that these women fulfil in family dynamics, it seeks to shed light on the transformative effects of their engagement in support groups, aiming to demonstrate how these networks promote resilience, empowerment, and healing for both the women and their families, thus offering a more comprehensive perspective on AUD's impact on society. Employing a qualitative narrative research design, the study utilized purposive sampling to select 36 participants from the northern, southern, and central regions of Kerala, India. Data collection was conducted through in-depth interviews using a semi-structured interview guide. The interviews, conducted initially in the local language, were transcribed into English and analyzed using the constant comparative method, ensuring that ethical considerations were upheld throughout the research process. The results of the study illuminate the multifaceted challenges faced by wives of individuals with AUD, including financial burdens, domestic violence, marital discord, and psychosocial issues. Notably, the participants reported a significant positive shift in their lives following their involvement in support groups, experiencing enhanced mental peace and tranquillity. This transformation enabled some participants to resume their education, engage with the community as role models and leaders, and reconstruct their lives. Most participants viewed their support group participation as a pivotal moment of hope restoration in their lives. The study reveals the necessity for integrating culturally sensitive support mechanisms into rehabilitation programs for families affected by AUD, advocating for broader adoption of support groups that cater to the specific sociocultural dynamics of affected communities.

5.
Can J Physiol Pharmacol ; 102(2): 105-115, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37979203

ABSTRACT

Previous studies from our laboratory revealed that the gaseous molecule hydrogen sulfide (H2S), a metabolic product of epigenetics, involves trans-sulfuration pathway for ensuring metabolism and clearance of homocysteine (Hcy) from body, thereby mitigating the skeletal muscle's pathological remodeling. Although the master circadian clock regulator that is known as brain and muscle aryl hydrocarbon receptor nuclear translocator like protein 1 (i.e., BMAL 1) is associated with S-adenosylhomocysteine hydrolase (SAHH) and Hcy metabolism but how trans-sulfuration pathway is influenced by the circadian clock remains unexplored. We hypothesize that alterations in the functioning of circadian clock during sleep and wake cycle affect skeletal muscle's biology. To test this hypothesis, we measured serum matrix metalloproteinase (MMP) activities using gelatin gels for analyzing the MMP-2 and MMP-9. Further, employing casein gels, we also studied MMP-13 that is known to be influenced by the growth arrest and DNA damage-45 (GADD45) protein during sleep and wake cycle. The wild type and cystathionine ß synthase-deficient (CBS-/+) mice strains were treated with H2S and subjected to measurement of trans-sulfuration factors from skeletal muscle tissues. The results suggested highly robust activation of MMPs in the wake mice versus sleep mice, which appears somewhat akin to the "1-carbon metabolic dysregulation", which takes place during remodeling of extracellular matrix during muscular dystrophy. Interestingly, the levels of trans-sulfuration factors such as CBS, cystathionine γ lyase (CSE), methyl tetrahydrofolate reductase (MTHFR), phosphatidylethanolamine N-methyltransferase (PEMT), and Hcy-protein bound paraoxonase 1 (PON1) were attenuated in CBS-/+ mice. However, treatment with H2S mitigated the attenuation of the trans-sulfuration pathway. In addition, levels of mitochondrial peroxisome proliferator-activated receptor-gamma coactivator 1-α (PGC 1-α) and mitofusin-2 (MFN-2) were significantly improved by H2S intervention. Our findings suggest participation of the circadian clock in trans-sulfuration pathway that affects skeletal muscle remodeling and mitochondrial regeneration.


Subject(s)
Circadian Clocks , Hydrogen Sulfide , Animals , Mice , Hydrogen Sulfide/metabolism , Cystathionine beta-Synthase , Muscle, Skeletal/metabolism , Gels , Cystathionine gamma-Lyase/metabolism , Phosphatidylethanolamine N-Methyltransferase
6.
Indian J Community Med ; 48(2): 230-237, 2023.
Article in English | MEDLINE | ID: mdl-37323752

ABSTRACT

Background: The novel Coronavirus is belonging to the family of SARS & MERS-CoV, the impact of the earlier is more dreadful as demonstrated by the steady increase in morbid cases. The average incubation period of COVID-19 is 1-14 days with a mean of 6 days. Aim - To evaluate predictors of mortality among COVID-19 patients. Objectives - 1. To assess risk predictors associated with mortality among COVID-19 patients 2. To a suggest prediction model for preventing mortality in future outbreaks. Materials and Methods: Study design - A case-control study. Study place -Tertiary care center, Nanded, Maharashtra. The present study included 400 cases that died off due to Covid-19 and 400 controls survived COVID-19 disease in a 1:1 proportion. Results: On admission, a significant difference was observed among cases and controls with reference to the percentage of SpO2 (p < 0.05). The proportion of associated co-morbidities among cases was very high i.e., 75.75% as compared to controls with a proportion of 29.25% co-morbidities. The median days of hospital stay were significantly lower in cases compared to controls (3 days vs 12 days, P < 0.001). Conclusion: Length of hospital stay (in days) was showing a significant difference among cases and control (3 days Vs 12 days); hospital stay was less (median 3 days) for cases, as they reported late and thus died earlier; hence concluded that early hospital admission will decrease chances of death due to COVID-19.

7.
Can J Physiol Pharmacol ; 101(8): 413-424, 2023 Aug 01.
Article in English | MEDLINE | ID: mdl-37207360

ABSTRACT

Porphyromonas gingivalis (P. gingivalis) is one of the most responsible periodontopathogenic bacteria in the development of periodontal disease (PD); however, its role in the development of other diseases still needs to be understood, specially its implications in the causation of cardiovascular pathogenesis. The aim of this study is to determine whether there is a direct association between P. gingivalis-induced PD with that of the development of cardiovascular disease, and whether a long-term administration of probiotic(s) could help improve the cardiovascular disease outcome. To test this hypothesis, we employed four different experimental groups of mice, designated as: Group I: Wild-type (WT) mice (C57BL/6J); Group II: Lactobacillus rhamnosus GG (LGG) (WT mice treated with a probiotic; LGG), Group III: PD (WT mice treated with P. gingivalis), and Group IV: PD + LGG (WT mice treated with P. gingivalis and LGG). PD was created by injecting 2 µL (i.e., 20 µg) of P. gingivalis lipopolysaccharide (LPS) intragingivally between the 1st and 2nd mandibular molars, two times a week for a total period of 6 weeks. The PD (LGG) intervention was done orally employing 2.5 × 105 CFU/day for a continuous period of 12 weeks. Immediately before the mice were sacrificed, echocardiography of the heart was performed, and after sacrifice, we collected serum samples, hearts, and the periodontal tissue. Histological assessment, cytokine analysis, and zymography of the cardiac tissue were performed. Results revealed inflammation of the heart muscle in the PD group that was marked by infiltration of neutrophils and monocytes, followed by fibrosis. Cytokine analysis of the mice sera revealed significantly elevated levels of tumor necrosis factor-α, IL-1ß, IL-6, and IL-17A in the PD group along with LPS-binding protein, and CD14. Most importantly, we observed elevated levels of P. gingivalis mRNAs in the heart tissues of PD mice. Zymographic analysis demonstrated matrix remodeling as revealed by increasing content of MMP-9 in the heart tissues of PD mice. Interestingly, LGG treatment was able to mitigate most of the pathological effects. The findings suggest that P. gingivalis could lead to cardiovascular system disorder and that probiotic intervention could alleviate, and most likely prevent bacteremia and its harmful effect(s) on the cardiovascular function.

8.
Int J Mol Sci ; 24(8)2023 Apr 15.
Article in English | MEDLINE | ID: mdl-37108465

ABSTRACT

Renal denervation (RDN) protects against hypertension, hypertrophy, and heart failure (HF); however, it is not clear whether RDN preserves ejection fraction (EF) during heart failure (HFpEF). To test this hypothesis, we simulated a chronic congestive cardiopulmonary heart failure (CHF) phenotype by creating an aorta-vena cava fistula (AVF) in the C57BL/6J wild type (WT) mice. Briefly, there are four ways to create an experimental CHF: (1) myocardial infarction (MI), which is basically ligating the coronary artery by instrumenting and injuring the heart; (2) trans-aortic constriction (TAC) method, which mimics the systematic hypertension, but again constricts the aorta on top of the heart and, in fact, exposes the heart; (3) acquired CHF condition, promoted by dietary factors, diabetes, salt, diet, etc., but is multifactorial in nature; and finally, (4) the AVF, which remains the only one wherein AVF is created ~1 cm below the kidneys in which the aorta and vena cava share the common middle-wall. By creating the AVF fistula, the red blood contents enter the vena cava without an injury to the cardiac tissue. This model mimics or simulates the CHF phenotype, for example, during aging wherein with advancing age, the preload volume keeps increasing beyond the level that the aging heart can pump out due to the weakened cardiac myocytes. Furthermore, this procedure also involves the right ventricle to lung to left ventricle flow, thus creating an ideal condition for congestion. The heart in AVF transitions from preserved to reduced EF (i.e., HFpEF to HFrEF). In fact, there are more models of volume overload, such as the pacing-induced and mitral valve regurgitation, but these are also injurious models in nature. Our laboratory is one of the first laboratories to create and study the AVF phenotype in the animals. The RDN was created by treating the cleaned bilateral renal artery. After 6 weeks, blood, heart, and renal samples were analyzed for exosome, cardiac regeneration markers, and the renal cortex proteinases. Cardiac function was analyzed by echocardiogram (ECHO) procedure. The fibrosis was analyzed with a trichrome staining method. The results suggested that there was a robust increase in the exosomes' level in AVF blood, suggesting a compensatory systemic response during AVF-CHF. During AVF, there was no change in the cardiac eNOS, Wnt1, or ß-catenin; however, during RDN, there were robust increases in the levels of eNOS, Wnt1, and ß-catenin compared to the sham group. As expected in HFpEF, there was perivascular fibrosis, hypertrophy, and pEF. Interestingly, increased levels of eNOS suggested that despite fibrosis, the NO generation was higher and that it most likely contributed to pEF during HF. The RDN intervention revealed an increase in renal cortical caspase 8 and a decrease in caspase 9. Since caspase 8 is protective and caspase 9 is apoptotic, we suggest that RDN protects against the renal stress and apoptosis. It should be noted that others have demonstrated a role of vascular endothelium in preserving the ejection by cell therapy intervention. In the light of foregoing evidence, our findings also suggest that RDN is cardioprotective during HFpEF via preservation of the eNOS and accompanied endocardial-endothelial function.


Subject(s)
Heart Failure , Hypertension , Mice , Animals , Caspase 8 , Caspase 9 , beta Catenin , Stroke Volume , Mice, Inbred C57BL , Kidney/pathology , Myocytes, Cardiac/pathology , Hypertension/pathology , Denervation , Hypertrophy/pathology , Fibrosis
9.
Mol Cell Biochem ; 478(1): 103-119, 2023 Jan.
Article in English | MEDLINE | ID: mdl-35731343

ABSTRACT

The ongoing pandemic (also known as coronavirus disease-19; COVID-19) by a constantly emerging viral agent commonly referred as the severe acute respiratory syndrome corona virus 2 or SARS-CoV-2 has revealed unique pathological findings from infected human beings, and the postmortem observations. The list of disease symptoms, and postmortem observations is too long to mention; however, SARS-CoV-2 has brought with it a whole new clinical syndrome in "long haulers" including dyspnea, chest pain, tachycardia, brain fog, exercise intolerance, and extreme fatigue. We opine that further improvement in delivering effective treatment, and preventive strategies would be benefited from validated animal disease models. In this context, we designed a study, and show that a genetically engineered mouse expressing the human angiotensin converting enzyme 2; ACE-2 (the receptor used by SARS-CoV-2 agent to enter host cells) represents an excellent investigative resource in simulating important clinical features of the COVID-19. The ACE-2 mouse model (which is susceptible to SARS-CoV-2) when administered with a recombinant SARS-CoV-2 spike protein (SP) intranasally exhibited a profound cytokine storm capable of altering the physiological parameters including significant changes in cardiac function along with multi-organ damage that was further confirmed via histological findings. More importantly, visceral organs from SP treated mice revealed thrombotic blood clots as seen during postmortem examination. Thus, the ACE-2 engineered mouse appears to be a suitable model for studying intimate viral pathogenesis thus paving the way for identification, and characterization of appropriate prophylactics as well as therapeutics for COVID-19 management.


Subject(s)
COVID-19 , Animals , Humans , Mice , Disease Models, Animal , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
10.
Physiol Rep ; 10(16): e15422, 2022 08.
Article in English | MEDLINE | ID: mdl-35986494

ABSTRACT

Ketone bodies (KB) serve as the food for mitochondrial biogenetics. Interestingly, probiotics are known to promote KB formation in the gut (especially those that belong to the Lactobacillus genus). Furthermore, Lactobacillus helps produce folate that lowers the levels of homocysteine (Hcy); a hallmark non-proteinogenic amino acid that defines the importance of epigenetics, and its landscape. In this study, we decided to test whether hydrogen sulfide (H2 S), another Hcy lowering agent regulates the epigenetic gene writer DNA methyltransferase (DNMT), eraser FTO and TET2, and thus mitigates the skeletal muscle remodeling. We treated hyperhomocysteinemic (HHcy, cystathionine beta-synthase heterozygote knockout; CBS+/- ) mice with NaHS (the H2 S donor). The results suggested multi-organ damage by HHcy in the CBS+/- mouse strain compared with WT control mice (CBS+/+ ). H2 S treatment abrogated most of the HHcy-induced damage. The levels of gene writer (DNMT2) and H3K9 (methylation) were higher in the CBS+/- mice, and the H2 S treatment normalized their levels. More importantly, the levels of eraser FTO, TET, and associated GADD45, and MMP-13 were decreased in the CBS+/- mice; however, H2 S treatment mitigated their respective decrease. These events were associated with mitochondrial fission, i.e., an increase in DRP1, and mitophagy. Although the MMP-2 level was lower in CBS+/- compared to WT but H2 S could further lower it in the CBS+/- mice. The MMPs levels were associated with an increase in interstitial fibrosis in the CBS+/- skeletal muscle. Due to fibrosis, the femoral artery blood flow was reduced in the CBS+/- mice, and that was normalized by H2 S. The bone and muscle strengths were found to be decreased in the CBS+/- mice but the H2 S treatment normalized skeletal muscle strength in the CBS+/- mice. Our findings suggest that H2 S mitigates the mitophagy-led skeletal muscle remodeling via epigenetic regulation of the gene writer and eraser function.


Subject(s)
Hydrogen Sulfide , Animals , Epigenesis, Genetic , Fibrosis , Hydrogen Sulfide/metabolism , Hydrogen Sulfide/pharmacology , Mice , Mitophagy , Muscle, Skeletal/metabolism
11.
Acta Orthop Belg ; 88(1): 151-159, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35512166

ABSTRACT

Fractures of the humeral shaft represent 2-4% of all fractures and functional bracing is the gold standard in conservative management. Complications like restricted shoulder range of motion and malunion of the proximal shaft fractures have however been reported. We conducted a retrospective chart re- view of patients treated with the extension casting method over a period of 16 years. Topographically, Garnavos P, M, D, PM and MD fractures and morphologically Simple, Complex and Intermediate fractures were included. Between 2003 and 2019, 74 patients were treated with extension casting. The fractures united at a mean of 10 weeks and there was no case of non-union. Humerus is one of the bones where conservative methodology is still very pertinent. Extension casting gives reproducible and good results. It also addresses patient comfort issues to a considerable extent by allowing shoulder motion and easier maintenance of personal hygiene.


Subject(s)
Humeral Fractures , Shoulder Fractures , Fracture Healing , Humans , Humeral Fractures/diagnostic imaging , Humeral Fractures/surgery , Humerus/surgery , Retrospective Studies , Shoulder , Shoulder Fractures/diagnostic imaging , Shoulder Fractures/surgery , Treatment Outcome
12.
Int J Mol Sci ; 24(1)2022 Dec 24.
Article in English | MEDLINE | ID: mdl-36613731

ABSTRACT

Although progressive wasting and weakness of respiratory muscles are the prominent hallmarks of Duchenne muscular dystrophy (DMD) and long-COVID (also referred as the post-acute sequelae of COVID-19 syndrome); however, the underlying mechanism(s) leading to respiratory failure in both conditions remain unclear. We put together the latest relevant literature to further understand the plausible mechanism(s) behind diaphragm malfunctioning in COVID-19 and DMD conditions. Previously, we have shown the role of matrix metalloproteinase-9 (MMP9) in skeletal muscle fibrosis via a substantial increase in the levels of tumor necrosis factor-α (TNF-α) employing a DMD mouse model that was crossed-bred with MMP9-knockout (MMP9-KO or MMP9-/-) strain. Interestingly, recent observations from clinical studies show a robust increase in neopterin (NPT) levels during COVID-19 which is often observed in patients having DMD. What seems to be common in both (DMD and COVID-19) is the involvement of neopterin (NPT). We know that NPT is generated by activated white blood cells (WBCs) especially the M1 macrophages in response to inducible nitric oxide synthase (iNOS), tetrahydrobiopterin (BH4), and tetrahydrofolate (FH4) pathways, i.e., folate one-carbon metabolism (FOCM) in conjunction with epigenetics underpinning as an immune surveillance protection. Studies from our laboratory, and others researching DMD and the genetically engineered humanized (hACE2) mice that were administered with the spike protein (SP) of SARS-CoV-2 revealed an increase in the levels of NPT, TNF-α, HDAC, IL-1ß, CD147, and MMP9 in the lung tissue of the animals that were subsequently accompanied by fibrosis of the diaphragm depicting a decreased oscillation phenotype. Therefore, it is of interest to understand how regulatory processes such as epigenetics involvement affect DNMT, HDAC, MTHFS, and iNOS that help generate NPT in the long-COVID patients.


Subject(s)
COVID-19 , Muscular Dystrophy, Duchenne , Animals , Humans , Mice , Matrix Metalloproteinase 9/metabolism , Mice, Inbred mdx , Tumor Necrosis Factor-alpha/metabolism , Post-Acute COVID-19 Syndrome , Neopterin/metabolism , COVID-19/pathology , SARS-CoV-2 , Muscular Dystrophy, Duchenne/genetics , Fibrosis , Muscle, Skeletal/metabolism , Disease Models, Animal
13.
Prateek Singh; Rajat Ujjainiya; Satyartha Prakash; Salwa Naushin; Viren Sardana; Nitin Bhatheja; Ajay Pratap Singh; Joydeb Barman; Kartik Kumar; Raju Khan; Karthik Bharadwaj Tallapaka; Mahesh Anumalla; Amit Lahiri; Susanta Kar; Vivek Bhosale; Mrigank Srivastava; Madhav Nilakanth Mugale; C.P Pandey; Shaziya Khan; Shivani Katiyar; Desh Raj; Sharmeen Ishteyaque; Sonu Khanka; Ankita Rani; Promila; Jyotsna Sharma; Anuradha Seth; Mukul Dutta; Nishant Saurabh; Murugan Veerapandian; Ganesh Venkatachalam; Deepak Bansal; Dinesh Gupta; Prakash M Halami; Muthukumar Serva Peddha; Gopinath M Sundaram; Ravindra P Veeranna; Anirban Pal; Ranvijay Kumar Singh; Suresh Kumar Anandasadagopan; Parimala Karuppanan; Syed Nasar Rahman; Gopika Selvakumar; Subramanian Venkatesan; MalayKumar Karmakar; Harish Kumar Sardana; Animika Kothari; DevendraSingh Parihar; Anupma Thakur; Anas Saifi; Naman Gupta; Yogita Singh; Ritu Reddu; Rizul Gautam; Anuj Mishra; Avinash Mishra; Iranna Gogeri; Geethavani Rayasam; Yogendra Padwad; Vikram Patial; Vipin Hallan; Damanpreet Singh; Narendra Tirpude; Partha Chakrabarti; Sujay Krishna Maity; Dipyaman Ganguly; Ramakrishna Sistla; Narender Kumar Balthu; Kiran Kumar A; Siva Ranjith; Vijay B Kumar; Piyush Singh Jamwal; Anshu Wali; Sajad Ahmed; Rekha Chouhan; Sumit G Gandhi; Nancy Sharma; Garima Rai; Faisal Irshad; Vijay Lakshmi Jamwal; MasroorAhmad Paddar; Sameer Ullah Khan; Fayaz Malik; Debashish Ghosh; Ghanshyam Thakkar; Saroj K Barik; Prabhanshu Tripathi; Yatendra Kumar Satija; Sneha Mohanty; Md. Tauseef Khan; Umakanta Subudhi; Pradip Sen; Rashmi Kumar; Anshu Bhardwaj; Pawan Gupta; Deepak Sharma; Amit Tuli; Saumya Ray Chaudhuri; Srinivasan Krishnamurthi; Prakash L; Ch V Rao; B N Singh; Arvindkumar Chaurasiya; Meera Chaurasiyar; Mayuri Bhadange; Bhagyashree Likhitkar; Sharada Mohite; Yogita Patil; Mahesh Kulkarni; Rakesh Joshi; Vaibhav Pandya; Amita Patil; Rachel Samson; Tejas Vare; Mahesh Dharne; Ashok Giri; Shilpa Paranjape; G. Narahari Sastry; Jatin Kalita; Tridip Phukan; Prasenjit Manna; Wahengbam Romi; Pankaj Bharali; Dibyajyoti Ozah; Ravi Kumar Sahu; Prachurjya Dutta; Moirangthem Goutam Singh; Gayatri Gogoi; Yasmin Begam Tapadar; Elapavalooru VSSK Babu; Rajeev K Sukumaran; Aishwarya R Nair; Anoop Puthiyamadam; PrajeeshKooloth Valappil; Adrash Velayudhan Pillai Prasannakumari; Kalpana Chodankar; Samir Damare; Ved Varun Agrawal; Kumardeep Chaudhary; Anurag Agrawal; Shantanu Sengupta; Debasis Dash.
Preprint in English | medRxiv | ID: ppmedrxiv-21267889

ABSTRACT

Data science has been an invaluable part of the COVID-19 pandemic response with multiple applications, ranging from tracking viral evolution to understanding the effectiveness of interventions. Asymptomatic breakthrough infections have been a major problem during the ongoing surge of Delta variant globally. Serological discrimination of vaccine response from infection has so far been limited to Spike protein vaccines used in the higher-income regions. Here, we show for the first time how statistical and machine learning (ML) approaches can discriminate SARS-CoV-2 infection from immune response to an inactivated whole virion vaccine (BBV152, Covaxin, India), thereby permitting real-world vaccine effectiveness assessments from cohort-based serosurveys in Asia and Africa where such vaccines are commonly used. Briefly, we accessed serial data on Anti-S and Anti-NC antibody concentration values, along with age, sex, number of doses, and number of days since the last vaccine dose for 1823 Covaxin recipients. An ensemble ML model, incorporating a consensus clustering approach alongside the support vector machine (SVM) model, was built on 1063 samples where reliable qualifying data existed, and then applied to the entire dataset. Of 1448 self-reported negative subjects, 724 were classified as infected. Since the vaccine contains wild-type virus and the antibodies induced will neutralize wild type much better than Delta variant, we determined the relative ability of a random subset of such samples to neutralize Delta versus wild type strain. In 100 of 156 samples, where ML prediction differed from self-reported uninfected status, Delta variant, was neutralized more effectively than the wild type, which cannot happen without infection. The fraction rose to 71.8% (28 of 39) in subjects predicted to be infected during the surge, which is concordant with the percentage of sequences classified as Delta (75.6%-80.2%) over the same period.

14.
Injury ; 51(7): 1413, 2020 07.
Article in English | MEDLINE | ID: mdl-32467045
15.
J Mol Graph Model ; 85: 304-315, 2018 10.
Article in English | MEDLINE | ID: mdl-30273773

ABSTRACT

Protic dicationic ionic liquids (PDILs) have attracted growing attention owing to their applications in domains of electrochemistry, proton conducting materials and other diverse areas. In the present work protic dicationic ionic liquids (PDILs) comprising of quaternary ammonium-, imidazolium- or pyrrolidinium-dications and bis(trifluoromethanesulfonyl)imide (Tf2N‾) anion have been modelled as the dication-(Tf2N)2 complexes. Electronic structure, vibrational and 1H NMR spectra of these complexes have been derived employing the M06-2x density functional theory. Theoretical calculations have shown that the strength of cation-anion binding follows the order: methylpyrrolidinum > quaternary ammonium > butylpyrrolidinium > imidazolium, which can be attributed to number and strength of N-H---O and C-H---O interactions. The dication-(Tf2N)2 complexes emerge with signature in frequency up-shift of the characteristic N-H stretching in their infrared spectra. Underlying molecular interactions are unveiled through natural bond orbital analyses, Quantum theory of atoms in molecules (QTAIM) and noncovalent interaction reduced density gradient method. The calculations have shown that cation-anion binding energies increase linearly with kinetic energy density component G(r) in QTAIM analysis and proton affinities in the PDILs. A correlation between change in free energies accompanying the dication-(Tf2N)2 complexes and proton affinities has also been established.


Subject(s)
Ammonium Compounds/chemistry , Anions/chemistry , Cations/chemistry , Hydrocarbons, Fluorinated/chemistry , Imidazoles/chemistry , Imides/chemistry , Ionic Liquids/chemistry , Kinetics , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Structure , Spectrum Analysis
16.
J Phys Chem A ; 122(30): 6225-6235, 2018 Aug 02.
Article in English | MEDLINE | ID: mdl-29965775

ABSTRACT

In the present work protic ionic liquids (PILs) composed of imidazolium-, quaternary ammonium-, or pyrrolidinium-dications and acetate (OAc-) anion have been modeled as the dication-anion complexes through the M06-2x based density functional theory. It has been shown that cation-anion interaction energies are larger for the PILs containing the quaternary ammonium cation, which can be attributed to strong hydrogen bonding from the terminal ammonium protons. Underlying N-H···O and C-H···O hydrogen bonding, electrostatic, and van der Waals interactions are unraveled using the natural bond orbital analyses in conjunction with the quantum theory of atoms in molecules (QTAIM) and noncovalent interaction index reduced density gradient methods. The ramifications of noncovalent binding to 1H NMR and vibrational spectra are presented. The calculations further demonstrate a linear correlation of the kinetic energy density parameter G( r) in QTAIM analysis with the characteristic frequency shift of -NH3+ stretching in the dication-anion complexes. Moreover, the chemical shifts (δH) in 1H NMR spectra from theory reveal larger deshielding; the corresponding δH value correlates well with proton affinities and cation-anion binding energies as well. Effect of solvent (DMSO) on structure, binding energies, and 1H NMR are presented. The shifts of the characteristic carbonyl and the terminal ammonium stretching vibrations accompanying the dication-anion complexes from gas phase calculations are in consonance with the self-consistent reaction field theory.

18.
J Phys Chem A ; 120(39): 7732-7744, 2016 Oct 06.
Article in English | MEDLINE | ID: mdl-27617590

ABSTRACT

Electronic structure, binding energies, and spectral characteristics of functionalized asymmetric dicationic ionic liquids (DILs) composed of quaternary ammonium cations substituted with the ethoxyethyl and allyl/3-phenylpropyl/methoxyethoxyethyl/pentyl functionalities on two different nitrogen centers of the dication and the bis(trifluoromethanesulfonyl)imide (Tf2N-) anion were derived employing the dispersion-corrected density functional theory. DILs based on methoxyethoxyethyl-substituted cation reveal stronger binding toward the Tf2N- anion. The measured glass transition temperatures are found to be strongly dependent on the cation-anion binding facilitated through noncovalent interactions with dominant contributions from the electrostatics and hydrogen bonding. The manifestations of these interactions to vibrational spectra, in particular, to SO2 and CF3 stretchings in the complexes are presented. It has been demonstrated that the frequency down (red)-shift of the SO2 stretching in these DILs with varying substituent follows the order: methoxyethoxyethyl (35 cm-1) > allyl (23 cm-1) > pentyl (20 cm-1) > 3-phenylpropyl (5 cm-1), which is consistent with the strength of cation-anion binding. The CF3 stretching of the anion exhibits the frequency shift in the opposite direction with its hierarchy being reversed to that of SO2 stretchings; the largest upshift (blue shift) of 60 cm-1 was predicted for the DILs composed of 3-phenlpropyl substituted dications. The direction of such frequency shift has been rationalized through the difference molecular electron density maps in conjunction with the electron density at the bond critical point in the quantum theory of atoms in molecules. The underlying cation-anion binding has been analyzed through charge distribution analysis characterized in terms of molecular electrostatic potential topography. Furthermore, the observed decomposition temperatures of DILs are shown to correlate well with the maximum surface electrostatic potential parameters in quantum theory of atoms in molecules.

19.
Article in English | MEDLINE | ID: mdl-26137451

ABSTRACT

BACKGROUND: Patient-centered perspectives on self-monitoring of blood glucose (SBMG) were assessed in adults with type 2 diabetes using a self-regulation conceptual framework. METHODS: Participants (N = 589; 53 % female) were adults with type 2 diabetes who were recruited during routine appointments at a diabetes outpatient clinic in the Southeastern/lower Midwestern region of the United States. RESULTS: Participant's had varying perceptions regarding provider recommendations for SMBG (responder n = 380). Personal blood glucose testing patterns were also varied and reports frequently omitted (responder n = 296). Respondent's most frequent personal pattern was to test "occasionally, as needed," which did not differ by insulin use status, gender or age. In those not prescribed insulin, HbA1c reflected better control in those testing at least once per week (p = .040) or with a blood glucose goal (p = .018). 30.9 % endorsed at least monthly perceived encounters with SMBG barriers, with higher reports by women (p = .005) and younger (p = .006) participants. Poorer glycemic control was observed for participants with more frequently reported scheduling (p = .025, .041) and discouragement (p = .003) barriers. CONCLUSIONS: Findings suggest that many may experience difficulty integrating SMBG into their lives and are unsure of recommendations and appropriate function. Research is needed to promote best practice recommendations for SMBG.

20.
J Craniovertebr Junction Spine ; 2(1): 32-7, 2011 Jan.
Article in English | MEDLINE | ID: mdl-22013373

ABSTRACT

AIM: To compare the osseous anatomy of the craniovertebral junction of a horse, deer, and tiger with that of a human being. The variation in the structure of bones in these animals is analyzed. MATERIALS AND METHODS: Various dimensions of the bones of the craniovertebral junction of the horse, deer, and tiger were quantitatively measured, and their differences with those of human bones were compared and analyzed. RESULTS: Apart from the sizes and weights, there are a number of structural variations in the bones of these animals that depend on their functional needs. The more remarkable difference in joint morphology is noticed in the occipitoatlantal joint. The occipitoatlantal articulation is remarkably large and deep, resembling a 'hinge joint' in all the three animals studied. The odontoid process is 'C shaped' in the deer and horse and is 'denslike' in the tiger and humans. The transverse processes of the atlas are in the form of large wings in all the three animals. The arches of the atlas are large and flat, but the traverse of the vertebral artery resembles, to an extent, to that of human vertebral artery. The rotatory movements of the head at the craniovertebral junction are wider ranged in the horse and deer as compared with those of the tiger and humans. The bones of the craniovertebral junction of all the three animals are adapted to the remarkable thickness and strength of the extensor muscles of the nape of the neck. CONCLUSIONS: Despite the wide variations in the size of the bones, the basic patterns of structure, vascular and neural relationship, and joint alignments have remarkable similarities and a definite pattern of differences.

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