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1.
Nature ; 628(8009): 844-853, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38570685

RESUMO

Mitochondria are critical modulators of antiviral tolerance through the release of mitochondrial RNA and DNA (mtDNA and mtRNA) fragments into the cytoplasm after infection, activating virus sensors and type-I interferon (IFN-I) response1-4. The relevance of these mechanisms for mitochondrial diseases remains understudied. Here we investigated mitochondrial recessive ataxia syndrome (MIRAS), which is caused by a common European founder mutation in DNA polymerase gamma (POLG1)5. Patients homozygous for the MIRAS variant p.W748S show exceptionally variable ages of onset and symptoms5, indicating that unknown modifying factors contribute to disease manifestation. We report that the mtDNA replicase POLG1 has a role in antiviral defence mechanisms to double-stranded DNA and positive-strand RNA virus infections (HSV-1, TBEV and SARS-CoV-2), and its p.W748S variant dampens innate immune responses. Our patient and knock-in mouse data show that p.W748S compromises mtDNA replisome stability, causing mtDNA depletion, aggravated by virus infection. Low mtDNA and mtRNA release into the cytoplasm and a slow IFN response in MIRAS offer viruses an early replicative advantage, leading to an augmented pro-inflammatory response, a subacute loss of GABAergic neurons and liver inflammation and necrosis. A population databank of around 300,000 Finnish individuals6 demonstrates enrichment of immunodeficient traits in carriers of the POLG1 p.W748S mutation. Our evidence suggests that POLG1 defects compromise antiviral tolerance, triggering epilepsy and liver disease. The finding has important implications for the mitochondrial disease spectrum, including epilepsy, ataxia and parkinsonism.


Assuntos
Alelos , DNA Polimerase gama , DNA Mitocondrial , Humanos , DNA Polimerase gama/genética , DNA Polimerase gama/metabolismo , Animais , Camundongos , DNA Mitocondrial/genética , Masculino , Feminino , Imunidade Inata/genética , SARS-CoV-2/imunologia , Herpesvirus Humano 1/imunologia , Tolerância Imunológica/genética , COVID-19/imunologia , COVID-19/virologia , COVID-19/genética , Técnicas de Introdução de Genes , Mitocôndrias/metabolismo , Mutação
2.
Cancer Rep (Hoboken) ; 7(4): e2011, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38644759

RESUMO

BACKGROUND: Noncommunicable diseases (NCDs) contribute significantly to global morbidity and mortality, with cancer being one of the leading causes. In this prospective observational study, we aimed to investigate the prevalence and impact of endocrine disorders, specifically diabetes and thyroid dysfunction, in patients with advanced metastatic cancer undergoing cancer-directed therapy. METHODS: Over 15 months, we recruited 100 histologically proven advanced metastatic cancer patients from the Department of Medical Oncology Haematology, All India Institute of Medical Sciences, Rishikesh, and conducted institutional-based prospective observational study. All participants over 18 years of age, treatment-naive, and potential candidates for systemic chemotherapy with an expected clinical survival of at least 6 months were included in the study. Patients with prior therapy, secondary neoplasms, and those unable to complete 3 months of palliative chemotherapy were excluded. Patients were assessed for diabetes and thyroid function at presentation, after 3 and 6 months of cancer-directed standard therapy. These data were analyzed, processed, and presented as results. RESULTS: The mean age of participants was 50.45 years, with a near-equal distribution of males and females. At baseline, 10% of the study population had preexisting endocrine disorders (2% hypothyroidism, 8% diabetes). By the end of 6 months, the prevalence increased to 18%, with females being more affected. Notably, the prevalence of new-onset endocrine disorders during cancer-directed therapy was only 3% for diabetes and 4% for thyroid dysfunction. CONCLUSION: Analysis of sociodemographic and cancer-related characteristics showed no significant association with changes in diabetic and thyroid status at 3 and 6 months. However, substance use, particularly smoking, was associated with an increased risk of diabetes development (p < .05). Cancer type and treatment regimen did not show statistically significant correlations with endocrine dysfunction. IMPLICATIONS: Our study highlights the importance of considering endocrine disorders in advanced metastatic cancer patients undergoing therapy. The prevalence of diabetes and thyroid dysfunction increased during cancer-directed therapy, particularly in females. Careful monitoring and timely intervention are essential to improve the quality of life for these patients. Further research is warranted to explore the long-term effects of cancer-directed therapy on endocrine health and develop tailored management strategies for this vulnerable population.


Assuntos
Doenças do Sistema Endócrino , Neoplasias , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Prevalência , Neoplasias/epidemiologia , Neoplasias/patologia , Adulto , Doenças do Sistema Endócrino/epidemiologia , Doenças do Sistema Endócrino/etiologia , Índia/epidemiologia , Idoso , Diabetes Mellitus/epidemiologia , Metástase Neoplásica
3.
Bioinformation ; 20(2): 165-169, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38497072

RESUMO

Data on the eating behaviors, knowledge, and attitudes of adolescent girls in Visnagar, India, focusing on the prevalence of non-communicable diseases [NCDs] and their association with dietary practices is of interest. Adolescence, a crucial developmental phase, sets the foundation for lifelong health habits, necessitating an understanding of the determinants influencing eating behaviors. The research aims to identify gaps in knowledge, attitudes, and practices [KAP], providing insights for culturally sensitive public health strategies. Through structured questionnaires and Likert scales, data were collected from a purposive sample of adolescent girls [ages 12-18] in a selected school. Descriptive statistics and correlation analyses were employed to assess knowledge, attitudes, and behaviors, considering demographic variables. Non-significant associations were found between these variables and demographics. The mean knowledge score was 25.11, reflecting a moderate level, while the mean attitudes score was 99.54, indicating generally positive attitudes. Adolescent girls demonstrated an overall mean behaviour score of 110.93, with a positive correlation [0.72] between knowledge and behaviors and a stronger correlation [0.99] between attitudes and behaviors. Findings highlight the universal importance of knowledge in influencing eating behaviors and emphasize the need for culturally tailored interventions considering regional influences. The study contributes valuable insights into the interplay of knowledge, attitudes, and behaviors related to eating disorders in adolescent girls, serving as a foundation for targeted public health strategies.

4.
Bioinformation ; 20(2): 160-164, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38497079

RESUMO

The initial weeks of a newborn's life are marked by rapid physiological and behavioural adjustments as the infant adapts to the external environment. This critical period necessitates attentive care, prompting exploration into traditional practices such as oil massage, which holds cultural significance and is believed to enhance neonatal well-being. Despite its prevalence, empirical evidence supporting the efficacy of oil massage remains limited. This study, conducted in a rural setting, aims to bridge traditional practices with evidence-based care, exploring the impact of oil massage on newborn behavioural responses. A quasi-experimental design involving 60 newborns (30 in each group) assessed behavioural responses through a pre and post-test approach. Results indicate a significant improvement in selected behavioural responses among newborns receiving oil massage, emphasizing its potential integration into routine care. The control group showed a pre-test mean of 14.83 (SD = 2.41) and a post-test mean of 16.23, while the experimental group exhibited a pre-test mean of 15.83 (SD = 1.80) and a post-test mean of 26.07. T-test values of 5.194 for the control group and 26.137 for the experimental group were indicative of statistically significant changes. The study contributes insights into neonatal care practices, urging further exploration of contextual intricacies and demographic influences on newborn behaviour.

5.
Indian J Endocrinol Metab ; 28(1): 35-42, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38533281

RESUMO

Introduction: Gastrointestinal neuropathies are frequently found in diabetic patients. The pathogenesis of diabetic gastroparesis (DG) is multifactorial. The usual treatment for DG includes dietary modifications, prokinetic and antiemetic agents. There is increasing demand for more effective medicines to treat DG. The current study was conducted on the Pistacia lentiscus stem extract to add to the armamentarium of DG treatment and to find the efficacy of P. lentiscus plant extract (mastic gum) in comparison to levosulpiride in DG for improvement in gastroparesis symptoms and gastric emptying scintigraphy (GES) in a single centric double-blind non-inferiority randomised control trial. Methods: Thirty-eight individuals were recruited and equally randomised into two study groups based on Gastroparesis Cardinal Symptom Index (GCSI) score and TC99 Radionuclide GES, mastic gum group and levosulpiride group. Both pre and post-intervention (8 weeks) GCSI scores were calculated, GES was performed to quantify the improvement in gastric emptying. Power analysis was performed using G*POWER software version 3.1.9.7 and data analysis using SPSS 23.0, variables measured in mean ± standard deviation (SD). Various statistical tests were used such as independent t-test, Chi-square test or Fisher's exact test, Wilcox Mann-Whitney test, analysis of variance (ANOVA) test, and posthoc pairwise tests. Results: The mastic gum is found effective in the improvement of 4 h gastric emptying percentage from the mean (SD) 76.60 (± 9.96) to mean (SD) 97.20 (2.17)% (P < 0.001). Mastic gum has the property of HbA1c reduction, which is more significant than that of levosulpiride (P = 0.044). Mastic gum also had significant Low density lipoprotein (LDL) (mg/dL) levels reduction, (P < 0.001), compared to levosupiride. An absolute increase was observed in haemoglobin (HB) level in mastic gum at a 2-month mean (SD) of 1.03 (0.77) (g/dL) (P-value <0.001). Conclusions: To our knowledge, this is the first study to compare the effect of levosulpiride with mastic gum concerning improvement in diabetic gastroparesis (DG) using GES. In the study, mastic gum was found to have great properties to improve DG with many important pleiotropic effects.

6.
Indian J Pharmacol ; 56(1): 4-9, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38454582

RESUMO

INTRODUCTION: Gastrointestinal neuropathies are frequently found in diabetic patients. AIM: The aim of this study was to find out the safety, adverse reactions, and long-term effectiveness of Pistacia lentiscus plant extract (mastic gum) in diabetic gastroparesis (DG) with respect to sustainable improvement in gastroparesis symptoms (Gastrointestinal Cardinal Symptom Index [GCSI] score) by observational follow-up study of a single-centric double-blind noninferiority randomized control trial. MATERIALS AND METHODS: Thirty-eight individuals were recruited and equally randomized in two study groups based on GCSI score and TC99 radionuclide gastric emptying scintigraphy (GES), i.e. the mastic gum group and the levosulpiride group. After 24 weeks, the GCSI score was recalculated in both the groups, and patients were evaluated for the safety, adverse reactions, and long-term effectiveness of mastic gum and the standard drug levosulpiride. RESULTS: In the extended study, mean GCSI score changes at 24 weeks were statistically significant (P < 0.001) (t-test) between the two groups. In the mastic gum arm, the change in mean GCSI score at 24 weeks was statistically nonsignificant mean ± (standard deviation [SD]) 16.7± (3.81) compared to the GCSI score at 2-month postintervention mean (SD) 16.35± (2.27) (intragroup P = 0.89) (repeated measures ANOVA). It strongly indicates that mastic gum provided a sustainable improvement in DG symptoms in comparison to levosulpiride, with excellent subjective well-being postintervention, without any obvious significant adverse effects. CONCLUSION: Six-month (24-week) interim analysis of patients suggests that mastic gum gives a sustainable improvement in DG symptoms without any obvious adverse effects as compared to levosulpiride.


Assuntos
Diabetes Mellitus , Neuropatias Diabéticas , Gastroparesia , Pistacia , Sulpirida , Humanos , Seguimentos , Esvaziamento Gástrico , Gastroparesia/tratamento farmacológico , Resina Mástique , Sulpirida/análogos & derivados
7.
J Clin Exp Hepatol ; 14(2): 101289, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38544762

RESUMO

Objectives: Obstructive sleep apnea (OSA) is an independent risk factor for non-alcoholic fatty liver disease. This study was planned to assess proportion of patients with OSA that have hepatic steatosis and fibrosis, as measured by transient elastography, to explore variables influencing their development and to find out the polysomnography parameters that predict the need for transient elastography screening in OSA. Methods: Consecutive participants having polysomnography proven OSA were included in the study after screening for eligibility criteria. Data of the polysomnography were scored manually following standard criteria. Participants were subjected to transient elastography (Fibroscan®) and serum investigations after diagnostic polysomnography. The polysomnography, fibroscan®, and laboratory data were tabulated and analyzed. Results: A total of 71 participants were enrolled. 16.9% participants had mild OSA, 28.2% had moderate OSA, and remaining participants had severe OSA. Liver steatosis was found in 63.4% participants while hepatic fibrosis was noted in 9.9%. Oxygen desaturation index (ODI), apnea-hypopnea index (AHI), and percentage of sleep spent below 90% oxygen saturation (T90) were significantly associated with the presence of hepatic steatosis and fibrosis. Receiver operating curve (ROC) showed that at the cut-offs of 73 events/hr, 13% and 72.2 events/hr, AHI, T90 and ODI, predicted hepatic fibrosis with area under ROC of 0.960, 0.944, and 0.933, respectively (P < 0.001). Conclusions: Patients with OSA are at increased risk for development of hepatic steatosis and fibrosis. ODI, AHI, and T90 during polysomnography predict the presence of underlying hepatic fibrosis.

8.
Indian J Orthop ; 58(3): 298-307, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38425822

RESUMO

Purpose: Malnourished adults with knee osteoarthritis (OA) have a lower propensity for physical activities, leading to post-surgical stress and poorer clinic-functional outcomes. The study is aimed to propose an integrative screening procedure for patients and to identify a subset of patients who are undernourished or at risk of undernutrition in the Indian population. Methods: A hospital-based cross-sectional study was conducted at a tertiary care, a university-level teaching hospital for seven months, which included knee OA patients above the age of 45 years, and the following criteria were evaluated anthropometric measurement and blood biochemical parameters and nutritional scoring system. Results: The current study reports a high prevalence of malnutrition (69.5%) in patients with knee OA in the Indian population based on blood biochemical levels, and late presenters are associated with poor nutritional status of an individual. A single gold standard blood biochemical test, serum albumin alone, reports many malnourished individuals in the population, and the remaining blood biochemical parameters may not yield any additional information. Mini nutritional assessment, mid-arm circumference, and mid-calf circumference are poor predictors of malnutrition, and we need a revised cut-off for our group of patients. Conclusion: In the cohort of OA Knee, the prevalence of malnutrition is high (69.5%) in the Indian population. Serum Albumin is the best parameter to detect the presence of malnutrition preoperatively, and MNS is not applicable to detect malnutrition in our subset of patients. The study recommends routinely measuring serum albumin levels in all patients to correct the nutritional abnormality preoperatively, resulting in better surgical outcomes and reduced post-operatively complications. Level of evidence: IV.

9.
Tuberculosis (Edinb) ; 146: 102492, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38364331

RESUMO

BACKGROUND: Data on the molecular epidemiology and transmission of drug-resistant Mycobacterium tuberculosis (MTB) in low-incidence settings with immigration from high-incidence settings is limited. METHOD: We included 115 drug-resistant (DR) MTB isolates with whole-genome sequencing data isolated in Finland between 2014 and 2021. Potential transmission clusters were identified using a threshold of 12 single-nucleotide polymorphisms (SNPs). Highly related clusters were identified using a threshold of 5 SNPs. RESULT: Of the 115 DR MTB isolates, 31 (27.0%) isolates were from Finnish-born cases and 84 (73.0%) were from foreign-born cases. The proportion of multidrug-resistant (MDR) MTB isolates (30/84, 35.7%) from foreign-born cases was higher than that of MDR MTB isolates from Finnish-born cases (8/31, 25.8%). Lineage 2 (40/115, 34.8%) and lineage 4 (40/115, 34.8%) were the most prevalent lineages. A total of 25 (21.7%) isolates were classified into eight potential transmission clusters (≤12 SNPs). Furthermore, five highly related clusters (≤5 SNPs) were identified, including three DR MTB isolates from Finnish-born cases and 14 DR isolates from foreign-born cases. CONCLUSION: The risk of DR MTB transmission between Finnish- and foreign-born persons is not negligible. Further research on clustering analysis in drug-susceptible MTB is worth to inform tuberculosis management and control in low-incidence settings with increasing immigration.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Humanos , Mycobacterium tuberculosis/genética , Antituberculosos/uso terapêutico , Finlândia/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose/microbiologia , Epidemiologia Molecular , Genótipo
10.
Microbiol Spectr ; 12(4): e0419922, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38363137

RESUMO

In response to the ongoing COVID-19 pandemic, the quest for coronavirus inhibitors has inspired research on a variety of small proteins beyond conventional antibodies, including robust single-domain antibody fragments, i.e., "nanobodies." Here, we explore the potential of nanobody engineering in the development of antivirals and diagnostic tools. Through fusion of nanobody domains that target distinct binding sites, we engineered multimodular nanobody constructs that neutralize wild-type SARS-CoV-2 and the Alpha and Delta variants at high potency, with IC50 values as low as 50 pM. Despite simultaneous binding to distinct epitopes, Beta and Omicron variants were more resistant to neutralization by the multimodular nanobodies, which highlights the importance of accounting for antigenic drift in the design of biologics. To further explore the applications of nanobody engineering in outbreak management, we present an assay based on fusions of nanobodies with fragments of NanoLuc luciferase that can detect sub-nanomolar quantities of the SARS-CoV-2 spike protein in a single step. Our work showcases the potential of nanobody engineering to combat emerging infectious diseases. IMPORTANCE: Nanobodies, small protein binders derived from the camelid antibody, are highly potent inhibitors of respiratory viruses that offer several advantages over conventional antibodies as candidates for specific therapies, including high stability and low production costs. In this work, we leverage the unique properties of nanobodies and apply them as building blocks for new therapeutic and diagnostic tools. We report ultra-potent SARS-CoV-2 inhibition by engineered nanobodies comprising multiple modules in structure-guided combinations and develop nanobodies that carry signal molecules, allowing rapid detection of the SARS-CoV-2 spike protein. Our results highlight the potential of engineered nanobodies in the development of effective countermeasures, both therapeutic and diagnostic, to manage outbreaks of emerging viruses.


Assuntos
COVID-19 , Anticorpos de Domínio Único , Glicoproteína da Espícula de Coronavírus , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Pandemias , Anticorpos de Domínio Único/genética , Anticorpos Neutralizantes , Anticorpos Antivirais
11.
Arch Microbiol ; 206(3): 118, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38393407

RESUMO

Candida albicans is a member of the ascomycetes class of fungi and it is an opportunistic pathogen species responsible for a wide range of fungal infections in humans. Bioinformatics and sequencing analysis of Candida proteomics has disclosed that around 69% proteome is still uncharacterized which needs to be annotated with functions. The NCBI-Genome has termed them as hypothetical proteins (HPs) in the whole proteome of Candida. Interpretation of this substantial portion of the proteome can reveal novel pharmacological targets for markers, drug development, and other therapeutics and so on. In this article, we have assigned functional annotation to these hypothetical proteins using bioinformatics methodologies. The advanced and robust computational models have been used to assign the preliminary functions to these putative HPs with high level of confidence. The findings of this study unveil some novel pharmacological targets for drug therapy and vaccines and it would help to identify novel molecular mechanisms underlying the fungal pathogenesis.


Assuntos
Candida albicans , Proteoma , Humanos , Candida albicans/genética , Proteoma/genética , Candida , Biologia Computacional , Proteínas Fúngicas/genética
12.
J Biomol Struct Dyn ; : 1-19, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38174578

RESUMO

After the emergence of the COVID-19 pandemic in late 2019, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has undergone a dynamic evolution driven by the acquisition of genetic modifications, resulting in several variants that are further classified as variants of interest (VOIs), variants under monitoring (VUM) and variants of concern (VOC) by World Health Organization (WHO). Currently, there are five SARS-CoV-2 VOCs (Alpha, Beta, Delta, Gamma and Omicron), two VOIs (Lambda and Mu) and several other VOIs that have been reported globally. In this study, we report a natural compound, Curcumin, as the potential inhibitor to the interactions between receptor binding domain (RBD(S1)) and human angiotensin-converting enzyme 2 (hACE2) domains and showcased its inhibitory potential for the Delta and Omicron variants through a computational approach by implementing state of the art methods. The study for the first time revealed a higher efficiency of Curcumin, especially for hindering the interaction between RBD(S1) and hACE-2 domains of Delta and Omicron variants as compared to other lead compounds. We investigated that the mutations in the RBD(S1) of VOC especially Delta and Omicron variants affect its structure compared to that of the wild type and other variants and therefore altered its binding to the hACE2 receptor. Molecular docking and molecular dynamics (MD) simulation analyses substantially supported the findings in terms of the stability of the docked complexes. This study offers compelling evidence, warranting a more in-depth exploration into the impact of these alterations on the binding of identified drug molecules with the Spike protein. Further investigation into their potential therapeutic effects in vivo is highly recommended.Communicated by Ramaswamy H. Sarma.

13.
Skeletal Radiol ; 53(3): 547-554, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37698625

RESUMO

OBJECTIVE: To explore the role of shear wave elastography of the tibial nerve as a potential ultrasonographic method for the diagnosis of tibial neuropathy in patients with type 2 diabetes. MATERIALS AND METHODS: This cross-sectional study included 50 subjects each in case (patients with diabetic tibial neuropathy diagnosed on the basis of clinical features and nerve conduction study) and control groups (non-diabetic non-neuropathic healthy volunteers). The exclusion criteria included the presence of type 1 diabetes, a known history of neuropathy from other causes except for type 2 diabetes, or a history of leg or ankle fracture. Cross-sectional area and shear wave velocity values of the tibial nerve were measured in both groups. Demographic details and body mass index were obtained in both groups and additionally, the duration of type 2 diabetes and HbA1c values in the case group were also noted. Wilcoxon Mann-Whitney U test was used to compare these variables in study groups. ROC curve analysis provided additional findings. RESULTS: Tibial nerve stiffness was significantly higher in the case group (p-value < 0.001). The study groups did not significantly differ in the Cross-sectional area of the tibial nerve (p-value 0.57). The case group exhibited a higher frequency of loss of the fascicular pattern of the tibial nerve (40% vs 18%, p-value 0.027). Duration of diabetes mellitus and HbA1c values did not significantly affect Shear wave velocity values in the case group. At the cut-off value of Shear wave velocity of 3.13 m/s, sensitivity and specificity to diagnose diabetic peripheral neuropathy were 94% and 88% respectively. CONCLUSION: Increased nerve stiffness is seen in patients with diabetic peripheral neuropathy. Shear wave elastography might prove as a novel noninvasive technology for screening/early diagnosis of diabetic peripheral neuropathy.


Assuntos
Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Técnicas de Imagem por Elasticidade , Neuropatia Tibial , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Estudos Transversais , Neuropatias Diabéticas/diagnóstico por imagem , Hemoglobinas Glicadas , Nervo Tibial/diagnóstico por imagem , Neuropatia Tibial/complicações
14.
Cureus ; 15(11): e48668, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38090447

RESUMO

Cryptococcal meningitis, a severe fungal infection, usually afflicts immunocompromised individuals, mainly those with acquired immunodeficiency syndrome (AIDS). However, rarely, immunocompetent individuals can develop the infection too. Here, we present a case of a human immunodeficiency virus (HIV)-seronegative individual without known immunocompromised states. This patient suffered from chronic headaches for five years before presenting to us, with multiple past consultations resulting in misdiagnoses of migraines and tension-type headaches (TTH). The patient had developed new-onset warning signs in the last month after which neuroimaging was done, which showed features of increased intracranial pressure. Cerebrospinal fluid (CSF) analysis revealed Cryptococcus neoformans. The patient received amphotericin B alongside flucytosine, and he underwent three therapeutic lumbar punctures (LP) to relieve symptoms from raised intracranial pressure. Within two weeks, he showed significant improvement in headaches and was discharged in a healthy state. The patient was doing fine two months post discharge. This case emphasizes the necessity of ruling out red flag signs before diagnosing primary headaches. In clinical practice, if any patient shows poor response to medications despite adequate compliance, a thorough evaluation is required to rule out serious causes of headache, with a low threshold for neuroimaging.

15.
J Gen Virol ; 104(12)2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38117290

RESUMO

Parapoxviruses (PPV) cause skin and mucous membrane lesions in several animal species, and of the five recognized PPVs, at least three are zoonotic. Equine PPV (EqPPV) is the sixth one initially described in humans in the United States and later in a severely sick horse in Finland in 2013-2015. In 2021-2022, a large-scale pustulo-vesicular pastern dermatitis outbreak occurred in horses all over Finland. This study aimed at analysing the outbreak, identifying and describing the causative agent, describing clinical signs, and searching for risk factors. EqPPV was identified as a probable causative agent and co-infections with several potentially pathogenic and zoonotic bacteria were observed. Histopathologically, suppurative and ulcerative dermatitis was diagnosed. Due to the lack of specific tests for this virus, we developed a novel diagnostic EqPPV-PCR with sensitivity of 10 copies/reaction. Based on a large proportion of the genome sequenced directly from clinical samples, very little variation was detected between the sequences of the case from 2013 and the cases from 2021 to 2022. Based on an epidemiological survey, the main risk factor for pastern dermatitis was having racehorses. Approximately one third of the horses at each affected stable got clinical dermatitis, manifesting as severe skin lesions. Skin lesions were also occasionally reported in humans, indicating potential zoonotic transmission. Case stables commonly reported attendance at race events before acquiring the disease. Survey also identified differences in practises between case and control stables. Taken together, these results enable a better preparedness, diagnostics, and guidelines for future outbreaks.


Assuntos
Coinfecção , Dermatite , Parapoxvirus , Humanos , Animais , Cavalos , Surtos de Doenças , Pele , Coinfecção/epidemiologia , Coinfecção/veterinária , Dermatite/epidemiologia , Dermatite/veterinária , Parapoxvirus/genética
16.
Viruses ; 15(12)2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38140633

RESUMO

In an age defined by rapid globalization and unprecedented technological advancements, the field of infectious diseases stands at the intersection of complex challenges and promising opportunities [...].


Assuntos
Doenças Transmissíveis , Humanos , Doenças Transmissíveis/epidemiologia
17.
Int J Mol Sci ; 24(24)2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38139170

RESUMO

We describe an investigation using structural mass spectrometry (MS) of the impact of two antibodies, 15497 and 15498, binding the highly flexible SARS-CoV-2 Nsp1 protein. We determined the epitopes and paratopes involved in the antibody-protein interactions by using hydrogen-deuterium exchange MS (HDX-MS). Notably, the Fab (Fragment antigen binding) for antibody 15498 captured a high energy form of the antigen exhibiting significant conformational changes that added flexibility over most of the Nsp1 protein. The Fab for antibody 15497, however, showed usual antigen binding behavior, revealing local changes presumably including the binding site. These findings illustrate an unusual antibody effect on an antigen and are consistent with the dynamic nature of the Nsp1 protein. Our studies suggest that this interaction capitalizes on the high flexibility of Nsp1 to undergo conformational change and be trapped in a higher energy state by binding with a specific antibody.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Deutério/química , Medição da Troca de Deutério/métodos , Espectrometria de Massas/métodos , Proteínas
18.
World J Diabetes ; 14(10): 1502-1513, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37970133

RESUMO

The gut microbiome is defined as an ecological community of commensal symbiotic and pathogenic microorganisms that exist in our body. Gut microbiome dysbiosis is a condition of dysregulated and disrupted intestinal bacterial homeostasis, and recent evidence has shown that dysbiosis is related to chronic inflammation, insulin resistance, cardiovascular diseases (CVD), type 2 diabetes mellitus (T2DM), and obesity. It is well known that obesity, T2DM and CVD are caused or worsened by multiple factors like genetic predisposition, environmental factors, unhealthy high calorie diets, and sedentary lifestyle. However, recent evidence from human and mouse models suggest that the gut microbiome is also an active player in the modulation of metabolic syndrome, a set of risk factors including obesity, hyperglycemia, and dyslipidemia that increase the risk for CVD, T2DM, and other diseases. Current research aims to identify treatments to increase the number of beneficial microbiota in the gut microbiome in order to modulate metabolic syndrome by reducing chronic inflammation and insulin resistance. There is increasing interest in supplements, classified as prebiotics, probiotics, synbiotics, or postbiotics, and their effect on the gut microbiome and metabolic syndrome. In this review article, we have summarized current research on these supplements that are available to improve the abundance of beneficial gut microbiota and to reduce the harmful ones in patients with metabolic syndrome.

19.
Indian J Community Med ; 48(5): 702-708, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37970160

RESUMO

Introduction: The interrelationship of diabetes with mental illness has increased in recent years. Diabetes-related distress is the emotional burden, stress, and worries associated with diabetes, which does not reach the threshold for depressive disorder. A diabetes self-management education (DSME) is a structured educational approach to improve glycemic control and diabetes-related distress. This study aimed to assess the effectiveness of DSME in comparison with usual diabetes care in improving glycemic control and diabetes-related distress. Material and Methods: This is a single-center, parallel randomized controlled trial. A total of 106 participants were recruited for both intervention and control groups with 53 participants each. The control group received only routine outpatient department (OPD) care. The intervention group received DSME in addition to routine OPD care. Diabetes-related distress and HbA1C were assessed after 3 months. The data were analyzed using IBM Statistical Package for the Social Sciences (SPSS) version 25. Per-protocol analysis was done. Results: Of 127 patients screened, 106 met the eligibility criteria and were randomized. At 3-month follow-up, the reduction in mean HbA1C, fasting blood sugar (FBS), postprandial blood sugar (PPBS), and diabetes distress were significant in the intervention group compared with the control group (p 0.001). The mean HbA1C reduction in the intervention group was significant (mean difference: -1.3, SD: 0.4). The mean DDS had decreased significantly in the intervention group from 2 to 1.2 (mean difference: -0.8, SD: 0.1). Conclusion: The DSME was effective in improving the glycemic control, diabetes-related distress, and self-care among type 2 diabetes (T2DM) mellitus patients.

20.
Cureus ; 15(10): e46960, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38021562

RESUMO

COVID-19, which is caused by the RNA virus, SARS-CoV-2, mainly affects the respiratory system and has a varied clinical presentation. However, several studies have shown that COVID-19 can also affect the gastrointestinal (GI) system. Patients can experience various GI symptoms, such as vomiting and diarrhea, and the virus has been detected in the stool samples of patients hospitalized with COVID-19. There have also been rare reports of COVID-19 presenting with isolated GI symptoms and lack of respiratory symptoms, and the virus has also been detected for prolonged periods in the fecal samples of COVID-19 patients. Major alterations in the gut microbiome in the form of depletion of beneficial organisms and an abundance of pathogenic organisms have been reported in the fecal samples of hospitalized COVID-19 patients. Although the US FDA has approved several drugs to manage COVID-19, their efficacy remains modest. So, there is a constant ongoing effort to investigate novel treatment options for COVID-19. Health supplements like probiotics, prebiotics, postbiotics, and synbiotics have been popularly known for their various health benefits. In this review, we have summarized the current literature, which shows the potential benefit of these health supplements to mitigate and/or prevent the clinical presentation of COVID-19.

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