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1.
J Med Virol ; 96(3): e29550, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38511593

RESUMO

Interindividual variation of human immunodeficiency virus (HIV) RNA setpoint in cerebrospinal fluid (CSF) and its determinants are poorly understood, but relevant for HIV neuropathology, brain reservoirs, viral escape, and reseeding after antiretroviral interruptions. Longitudinal multicentric study on demographic, clinical, and laboratory correlates of CSF HIV RNA in 2000 follow-up visits from 597 people with HIV (PWH) off antiretroviral therapy (ART) and with plasma HIV RNA > the lower limit of quantification (LLQ). Factors associated with CSF control (CSFC; CSF HIV RNA < LLQ while plasma HIV RNA > LLQ) and with CSF/plasma discordance (CSF > plasma HIV RNA > LLQ) were also assessed through mixed-effects models. Posthoc and sensitivity analyses were performed for persistent CSFC and ART-naïve participants, respectively. Over a median follow-up of 2.1 years, CSF HIV RNA was associated with CD4+ and CD8+ T cells, CSF leukocytes, blood-brain barrier (BBB) integrity, biomarkers of iron and lipid metabolism, serum globulins, past exposure to lamivudine, and plasma HIV RNA (model p < 0.0001). CSFC (persistent in 7.7% over 3 years) and CSF/plasma discordance (persistent in <0.01% over 1 year) were variably associated with the same parameters (model p < 0.001). Sensitivity analyses confirmed most of the previous associations in participants never exposed to ART. Persistent CSFC was associated with higher CD4+ T-cell count nadir (p < 0.001), lower serum globulins (p = 0.003), and lower CSF leukocytes (p < 0.001). Without ART, one in 13 PWH had persistently undetectable CSF HIV RNA, while persistent CSF/plasma discordance was extremely rare over years. Immune responses, inflammation, BBB permeability, and iron and lipid metabolism were all associated with HIV replication in CSF.


Assuntos
Infecções por HIV , HIV-1 , Humanos , HIV-1/genética , RNA Viral , Ferro , Soroglobulinas/metabolismo , Soroglobulinas/uso terapêutico , Carga Viral
2.
J Neurovirol ; 29(1): 45-52, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36729300

RESUMO

Despite the fact that many coinfections in people with HIV (PWH) are treatable or suppressible, they may still impact neurocognitive (NC) functioning. Here, we aim to evaluate the presence of latent/treated coinfections and their association with NC functioning in a cohort of PWH in Zambia. We carried out a cross-sectional, nested study involving 151 PWH with viral suppression, and a normative sample of 324 adults without HIV. Plasma samples from PWH who underwent a comprehensive NC assessment were evaluated for the presence of treated/latent coinfections that are common in Zambia. Information about treated pulmonary tuberculosis (TB) was obtained from participants' clinical charts. Overall, PWH differed significantly from the HIV seronegatives on all neuropsychological domains except for fine motor control. ANOVA comparisons of all 3 HIV + groups' demographically corrected mean NC T-scores showed that the HIV + /TB + group had the poorest NC functioning in the following domains: executive functioning (F = 4.23, p = 0.02), working memory (F = 5.05, p = 0.002), verbal fluency (F = 4.24, p = 0.006), learning (F = 11.26, p < 0.001), delayed recall (F = 4.56, p = 0.01), and speed of information processing (F = 5.16, p = 0.005); this group also was substantially worse on the total battery (global mean T-scores; F = 8.02, p < 0.001). In conclusion, treated TB coinfection in PWH was associated with worse NC performance compared to both those with antibodies against other coinfections and without. PWH with antibodies for other coinfections (HIV + /CI +) showed somewhat better NC performance compared to those without (HIV + /CI -), which was not expected, although comparisons with the HIV + /CI + group are limited by its lack of specificity regarding type of coinfection being represented.


Assuntos
Coinfecção , Infecções por HIV , Adulto , Humanos , Infecções por HIV/complicações , Coinfecção/complicações , Zâmbia , Estudos Transversais , Função Executiva
3.
Transpl Infect Dis ; 25(6): e14167, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37922371

RESUMO

BACKGROUND: Post-acute sequelae of coronavirus disease 2019 (COVID-19) (PASC), defined as prolonged symptoms following an episode of COVID-19, is not well-characterized in solid organ transplant recipients (SOTR). In this study, we aimed to assess the prevalence of PASC in SOTR, its descriptive characteristics, and associated risk factors. METHODS: We retrospectively identified SOTRs with acute COVID-19 between June 1, 2020 and April 15, 2022, and abstracted demographic and medical history, characteristics of acute COVID-19 illness, and COVID-19 vaccination status. We defined PASC as ongoing/new symptoms present at 6 weeks or longer following acute COVID-19 diagnosis. RESULTS: Among 208 SOTRs with acute COVID-19, 72 (35%) developed PASC. Common symptoms were respiratory symptoms (67%), headache (40%), and difficulty concentrating (10%). Severe acute COVID-19 disease and presence of respiratory symptoms were associated with higher odds of PASC in multivariable analyses, while receipt of at least one COVID-19 vaccination prior to transplantation was protective. CONCLUSION: We found that PASC occurs in about a third of SOTRs with acute COVID-19 and has similar symptoms as described previously in immunocompetent hosts. Pre-transplant vaccination may be protective. Further prospective multicenter studies are needed.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Transplante de Órgãos , Transplantados , Humanos , COVID-19/epidemiologia , Teste para COVID-19 , Vacinas contra COVID-19/administração & dosagem , Progressão da Doença , Síndrome de COVID-19 Pós-Aguda/epidemiologia , Estudos Retrospectivos
4.
Methods ; 195: 57-71, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33453392

RESUMO

SARS-CoV-2, the virus that causes COVID-19 consists of several enzymes with essential functions within its proteome. Here, we focused on repurposing approved and investigational drugs/compounds. We targeted seven proteins with enzymatic activities known to be essential at different stages of the viral cycle including PLpro, 3CLpro, RdRP, Helicase, ExoN, NendoU, and 2'-O-MT. For virtual screening, energy minimization of a crystal structure of the modeled protein was carried out using the Protein Preparation Wizard (Schrodinger LLC 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs and investigational molecules (n = 5903). The screening was performed against viral targets using three sequential docking modes (i.e., HTVS, SP, and XP). Virtual screening identified ∼290 potential inhibitors based on the criteria of energy, docking parameters, ligand, and binding site strain and score. Drugs specific to each target protein were further analyzed for binding free energy perturbation by molecular mechanics (prime MM-GBSA) and pruning the hits to the top 32 candidates. The top lead from each target pool was further subjected to molecular dynamics simulation using the Desmond module. The resulting top eight hits were tested for their SARS-CoV-2 anti-viral activity in-vitro. Among these, a known inhibitor of protein kinase C isoforms, Bisindolylmaleimide IX (BIM IX), was found to be a potent inhibitor of SARS-CoV-2. Further, target validation through enzymatic assays confirmed 3CLpro to be the target. This is the first study that has showcased BIM IX as a COVID-19 inhibitor thereby validating our pipeline.


Assuntos
Antivirais/administração & dosagem , Proteases 3C de Coronavírus/antagonistas & inibidores , Sistemas de Liberação de Medicamentos/normas , Indóis/administração & dosagem , Maleimidas/administração & dosagem , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/enzimologia , Antivirais/metabolismo , Proteases 3C de Coronavírus/química , Proteases 3C de Coronavírus/metabolismo , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Reposicionamento de Medicamentos/métodos , Reposicionamento de Medicamentos/normas , Ensaios de Triagem em Larga Escala/métodos , Ensaios de Triagem em Larga Escala/normas , Humanos , Indóis/química , Indóis/metabolismo , Maleimidas/química , Maleimidas/metabolismo , Simulação de Acoplamento Molecular/métodos , Simulação de Acoplamento Molecular/normas , Estrutura Secundária de Proteína , Reprodutibilidade dos Testes , SARS-CoV-2/química
5.
J Neurovirol ; 25(6): 792-799, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31281947

RESUMO

Infections with HIV and hepatitis C virus (HCV) can individually and jointly contribute to neurocognitive impairment (NCI). Rates of NCI in HIV/HCV-coinfected persons range from 40 to 63% but its correlates have not been described. In this study, we examined HIV/HCV-coinfected adults on antiretroviral therapy (ART) with undetectable HIV RNA in blood (n = 412) who were assessed using a comprehensive neuropsychological test battery. Demographics, host and viral biomarkers, and markers of liver dysfunction were compared between impaired (n = 198) and unimpaired (n = 214) participants using logistic regression. The cohort was predominantly middle-aged men, half of whom (48%) had NCI. The odds of NCI increased by almost two-fold when serum albumin was < 4 g/dL, 1.7-fold when alanine aminotransferase (ALT) levels were > 50 IU/L, and 2.2-fold with every unit increase in log10 AST to Platelet Ratio Index (APRI). These readily available clinical biomarkers of NCI measure hepatic injury and/or dysfunction, suggesting a mechanism for the effects of HCV infection on NCI. They may identify patients at increased risk of NCI who could be prioritized for early initiation of HCV treatment to protect or improve cognition.


Assuntos
Disfunção Cognitiva/virologia , Infecções por HIV/complicações , Hepatite C/complicações , Fígado/fisiopatologia , Coinfecção , Feminino , Hepacivirus , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade
6.
Clin Infect Dis ; 67(5): 770-777, 2018 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-29506084

RESUMO

Background: Cytomegalovirus (CMV) has been linked to higher risk of cardiovascular disease and mortality. We aimed to determine if CMV is associated with neurocognitive performance in adults infected with human immunodeficiency virus (HIV). Methods: In this cross-sectional analysis, anti-CMV immunoglobulin G (IgG) concentrations in blood and CMV DNA copies in blood and cerebrospinal fluid (CSF) were measured in stored specimens of 80 HIV-infected adults who were previously assessed with a comprehensive neurocognitive test battery. Thirty-eight were taking suppressive antiretroviral therapy (ART) and 42 were not taking ART. A panel of 7 soluble biomarkers was measured by immunoassay in CSF. Results: Anti-CMV IgG concentrations ranged from 5.2 to 46.1 IU/mL. CMV DNA was detected in 7 (8.8%) plasma specimens but in no CSF specimens. Higher anti-CMV IgG levels were associated with older age (P = .0017), lower nadir CD4+ T-cell count (P < .001), AIDS (P < .001), and higher soluble CD163 (P = .009). Higher anti-CMV IgG levels trended toward an association with worse neurocognitive performance overall (P = .059). This correlation was only present in those taking suppressive ART (P = .0049). Worse neurocognitive performance remained associated with higher anti-CMV IgG levels after accounting for other covariates in multivariate models (model P = .0038). Detectable plasma CMV DNA was associated with AIDS (P = .05) but not with neurocognitive performance. Conclusions: CMV may influence neurocognitive performance in HIV-infected adults taking suppressive ART. Future clinical trials of anti-CMV therapy should help to determine whether the observed relationships are causal.


Assuntos
Anticorpos Antivirais/sangue , Infecções por Citomegalovirus/complicações , Infecções por HIV/tratamento farmacológico , Imunoglobulina G/sangue , Transtornos Neurocognitivos/etiologia , Adulto , Fatores Etários , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Biomarcadores/líquido cefalorraquidiano , Estudos de Coortes , Estudos Transversais , Citomegalovirus , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/imunologia , DNA Viral/sangue , DNA Viral/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Testes de Estado Mental e Demência , Transtornos Neurocognitivos/virologia , Carga Viral
8.
J Neurovirol ; 23(5): 750-755, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28681344

RESUMO

The validity of a comprehensive international neuropsychological (NP) test battery for detection of HIV-associated neurocognitive disorders (HAND) in a Tamil speaking southern Indian cohort (69 HIV+ and 67 HIV-) was explored. The prevalence of HAND was significantly higher in the HIV+ vs. HIV- group (33 vs.13%; p < 0.01). Impairment rates were highest in the motor and speed of information processing domains. An NP battery translated into Tamil appears to be a valid tool for assessing HAND because the prevalence it found of HAND in southern India is similar to that found elsewhere.


Assuntos
Complexo AIDS Demência/diagnóstico , Complexo AIDS Demência/epidemiologia , Testes Neuropsicológicos , Adulto , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
9.
Clin Infect Dis ; 63(12): 1655-1660, 2016 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-27794019

RESUMO

BACKGROUND: Human immunodeficiency virus (HIV)-associated neurocognitive disorders persist despite suppressive antiretroviral therapy (ART). Because latent Toxoplasma infection (LTI) may adversely impact brain function, we investigated its impact on neurocognitive impairment (NCI) in people living with HIV disease. METHODS: Two hundred sixty-three HIV-infected adults underwent comprehensive neurocognitive assessments and had anti-Toxoplasma gondii immunoglobulin G (anti-Toxo IgG) measured by qualitative and quantitative enzyme-linked immunosorbent assays. RESULTS: Participants were mostly middle-aged white men who were taking ART (70%). LTI was detected in 30 (11.4%) participants and was associated with a significantly greater prevalence of global NCI (LTI positive [LTI+] = 57% and LTI negative [LTI-] = 34%) (odds ratio, 1.67; 95% confidence interval, 1.17-2.40; P = .017). Deficits were more prevalent in the LTI+ vs the LTI- group in 6 of 7 cognitive domains with statistical significance reached for delayed recall (P < .01). The probability of NCI increased with higher CD4+ T-cell counts among LTI+ individuals but with lower CD4+ T-cell counts in LTI- persons. A strong correlation (r = .93) between anti-Toxo IgG levels and global deficit score was found in a subgroup of 9 patients. Biomarkers indicative of central nervous system inflammation did not differ between LTI+ and LTI- participants. CONCLUSIONS: In this cross-sectional analysis, LTI was associated with NCI, especially in those with higher CD4+ T-cell counts. Longitudinal studies to investigate the role of neuroinflammation and neuronal injury in LTI patients with NCI and trials of anti-Toxoplasma therapy should be pursued.


Assuntos
Anticorpos Antiprotozoários/sangue , Infecções por HIV/complicações , Imunoglobulina G/sangue , Transtornos Neurocognitivos/etiologia , Toxoplasmose/complicações , Adulto , Fármacos Anti-HIV/uso terapêutico , Anticorpos Antiprotozoários/imunologia , Biomarcadores/líquido cefalorraquidiano , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/fisiopatologia , Humanos , Imunoglobulina G/imunologia , Mediadores da Inflamação , Masculino , Transtornos Neurocognitivos/imunologia , Transtornos Neurocognitivos/parasitologia , Transtornos Neurocognitivos/virologia , Prognóstico , Fatores de Risco , Toxoplasma , Toxoplasmose/imunologia , Toxoplasmose/fisiopatologia
10.
Cureus ; 16(4): e57372, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38694628

RESUMO

BACKGROUND: Sacroiliitis, characterized by inflammation of the sacroiliac joints, poses significant challenges in management, especially in patients unresponsive to standard therapies like non-steroidal anti-inflammatory drugs (NSAIDs) and physical therapy. This study aimed to evaluate the efficacy of antibiotic therapy in such patients, addressing a critical gap in the current treatment approach. METHODS: A total of 360 patients with lower back pain who presented to the outpatient department (OPD) of the Department of Orthopedics of a medical college in Northern India for six months were included in this study. With meticulous history taking, clinical examination, and radiological evaluation, 59 patients were diagnosed with sacroiliitis, out of which 31 were males and 28 were females, aged between 20 and 40 years, and were enrolled in this cross-sectional comparative study. Patients were divided into two groups: a control group (21 patients) receiving conventional treatment without antibiotics and a study group (38 patients) receiving conventional treatment plus antibiotics (who gave consent for treatment with antibiotics). The primary outcome was assessed using the Japanese Orthopaedic Association (JOA) score, with evaluations conducted at baseline, one month, and three months. Recovery rates were also calculated. SPSS trial software version 27 (IBM Corp., Armonk, NY) was used for statistical analysis. RESULTS: Both groups exhibited improvement in JOA scores over time. At the one-month and three-month follow-ups, the mean JOA scores and recovery rates showed no statistically significant difference between the control and study groups (p-values > 0.05). Adverse effects related to antibiotic use were not significant. CONCLUSION: The study concludes that the addition of antibiotics to the conventional treatment regimen for sacroiliitis does not provide significant benefit in terms of functional recovery or pain relief in patients non-responsive to NSAIDs and/or physical therapy. These findings underscore the importance of a targeted treatment approach based on the specific etiology of sacroiliitis and caution against unnecessary antibiotic use.

11.
J Orthop Case Rep ; 14(9): 45-48, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39253645

RESUMO

Introduction: Giant cell tumor (GCT) is a benign locally aggressive tumor with features of frequent recurrence and metastatic potential. GCT of small bones of hand and feet is rare with high recurrence and potential to metastasis. This study aims to provide a case report of GCT of the first metatarsal treated with wide excision, autologous fibular grafting, and fixation with locking plate. Case Report: An 18-year-old male patient presented with progressive swelling over the dorsomedial aspect of foot for 1 year. Upon clinical examination, the swelling was firm with local signs suggestive of a benign bony tumor arising from the base of first metatarsal of the left foot. Radiology reveals an expansile osteolytic lesion arising from the base of 1st metatarsal with coarse septations and features suggestive of a benign bone lesion. A core biopsy was obtained under local anesthesia and histopathology report suggested a GCT. Surgical intervention by en bloc excision and reconstruction by fibular autograft and stabilized with a locking plate was done. The patient was given a below-knee cast for 6 weeks postoperatively. Full weight bearing was started after 6 weeks. At 12 months of follow-up, the graft was well taken up and there were no signs of recurrence both clinically and radiologically. Conclusion: GCT of 1st metatarsal is a rare entity with higher recurrence rate compared to conventional GCT. En bloc excision and autologous fibular graft with plate fixation are preferred treatment options.

12.
Bioresour Technol ; 413: 131398, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39236907

RESUMO

Utilization of organic community wastes towards deriving sustainable renewable energy and adequate disposal of the residual has been an important topic of investigation. Anaerobic digestion and co-digestion of rice-derived food waste and animal manure for sustainable biogas generation is crucial from the view-point of community consumption. This paper presents an extensive review of the important and recent contributions in the related areas. The critical physico-chemical parameters involved in such digestion process are analyzed, including temperature, carbon-nitrogen ratio, microorganisms, pH, substrate characteristics, organic loading rate, hydraulic retention time, volatile fatty acids, ammonia, and light/heavy metal ions. Studies implied that the optimum yield of biogas production could be achieved only when the values of the parameters exist in the specific ranges. Few recent studies highlighted the use of emerging techniques including micro-aerobic system, additives, laser radiation, bio-electrochemical field, among others for efficiency enhancement of the digestion process and optimum yield. The entire study provided a set of important conclusions and future research directives are as well proposed.


Assuntos
Esterco , Oryza , Oryza/química , Animais , Anaerobiose , Biocombustíveis , Eliminação de Resíduos/métodos , Alimentos , Resíduos , Perda e Desperdício de Alimentos
13.
Indian J Orthop ; 58(6): 619-636, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38812876

RESUMO

Purpose of the study: This study aimed to reach a consensus for ideal surgical treatment of discoid lateral meniscus (DLM) and to evaluate its long term surgical and radiological outcome. Methods: All authors independently searched for peer reviewed publications with keywords like discoid lateral meniscus, tibial menisci abnormalities, tibial menisci surgery and clinical outcome and their representative Medical Subjects Headings (MeSH) in databases of PubMed, EBSCO, Cochrane Central Register of Controlled Trials, from inception to December 2022. Original articles in English language on discoid lateral meniscus reporting clinical, surgical, or radiological outcomes with five or more years of follow-up were included in this systematic review. Study details and outcome data were analysed according to the age, follow-up period, kind of surgery, DLM type, and alignment. Results: Our search strategy yielded 654 articles in PubMed, 222 articles in EBSCO and 5 articles in CENTRAL i.e. a total of 881 articles. After detailed assessment and screening, 12 articles were included in the final analysis, which included 444 DLM cases. The mean patient age at surgery ranged from 9.9 to 35.9 years, and the mean follow-up period ranged from 5.2 to 16 years. Partial meniscectomy and meniscoplasty are the recommended treatment because of the concerns of degenerative arthritis development after the total and subtotal meniscectomies. Two studies have documented better results with meniscal allograft transplantation. Conclusion: Satisfactory clinico-radiological outcome can be obtained after surgical treatment of discoid lateral meniscus with meniscus reshaping and repair of peripheral unstable part. Meniscal allograft transplantation (MAT) is gaining popularity in patients with total meniscectomy with satisfactory long term functional outcome.

14.
AIDS ; 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39120536

RESUMO

BACKGROUND: Neurocognitive impairment (NCI) may occur during and persist even after recovery from HIV-related CNS co-infections such as toxoplasmic encephalitis (TE). The long-term cognitive effects of TE and latent toxoplomasmic infections (LTI) among persons with HIV (PWH) are unknown. We measured longitudinal effects on NC functioning in PWH with TE compared to LTI or no toxoplasmal infection. METHODS: PWH (n = 345) followed in two longitudinal cohort studies underwent comprehensive neurocognitive assessments and an anti-Toxoplamic IgG assay. Participants were classified into one of three groups: TE+ (n = 39), LTI+ (n = 34), LTI- (n = 272). The primary outcome was change in neurocognitive function between baseline and 7-year visit. RESULTS: The mean age was 48 ±â€Š11 years, mean educational level 13 ±â€Š3 years, and 13% were female. TE+ patients were less likely to have undetectable viral loads (≤50 copies/mL) and had lower absolute CD4 counts. The TE+ group had the highest prevalence of NCI globally and in domains of verbal, executive function, learning, recall, working memory, processing speed and motor at baseline and at 7-year follow-up. Changes in longitudinal NC function over 7 years were small and did not differ significantly among all groups, except that speed of information processing improved more in TE+ compared with LTI- participants. CONCLUSIONS: PWH with a history of TE had cognitive impairment over a broad range of severity at both baseline and last follow-up. Changes in cognition from baseline to last examination in all groups were minimal and did not differ significantly among the groups with the exception of speed of information processing.

15.
J Neuroimmune Pharmacol ; 19(1): 25, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38789639

RESUMO

Based on emerging evidence on the role for specific single-nucleotide variants (SNVs) in EIF2AK3 encoding the integrated stress response kinase PERK, in neurodegeneration, we assessed the association of EIF2AK3 SNVs with neurocognitive performance in people with HIV (PWH) using a candidate gene approach. This retrospective study included the CHARTER cohort participants, excluding those with severe neuropsychiatric comorbidities. Genome-wide data previously obtained for 1047 participants and targeted sequencing of 992 participants with available genomic DNA were utilized to interrogate the association of three noncoding and three coding EIF2AK3 SNVs with the continuous global deficit score (GDS) and global neurocognitive impairment (NCI; GDS ≥ 0.5) using univariable and multivariable methods, with demographic, disease-associated, and treatment characteristics as covariates. The cohort characteristics were as follows: median age, 43.1 years; females, 22.8%; European ancestry, 41%; median CD4 + T cell counts, 175/µL (nadir) and 428/µL (current). At first assessment, 70.5% used ART and 68.3% of these had plasma HIV RNA levels ≤ 200 copies/mL. All three noncoding EIF2AK3 SNVs were associated with GDS and NCI (all p < 0.05). Additionally, 30.9%, 30.9%, and 41.2% of participants had at least one risk allele for the coding SNVs rs1805165 (G), rs867529 (G), and rs13045 (A), respectively. Homozygosity for all three coding SNVs was associated with significantly worse GDS (p < 0.001) and more NCI (p < 0.001). By multivariable analysis, the rs13045 A risk allele, current ART use, and Beck Depression Inventory-II value > 13 were independently associated with GDS and NCI (p < 0.001) whereas the other two coding SNVs did not significantly correlate with GDS or NCI after including rs13045 in the model. The coding EIF2AK3 SNVs were associated with worse performance in executive functioning, motor functioning, learning, and verbal fluency. Coding and non-coding SNVs of EIF2AK3 were associated with global NC and domain-specific performance. The effects were small-to-medium in size but present in multivariable analyses, raising the possibility of specific SNVs in EIF2AK3 as an important component of genetic vulnerability to neurocognitive complications in PWH.


Assuntos
Infecções por HIV , Polimorfismo de Nucleotídeo Único , eIF-2 Quinase , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Disfunção Cognitiva/genética , Estudos de Coortes , eIF-2 Quinase/genética , Infecções por HIV/genética , Infecções por HIV/complicações , Infecções por HIV/psicologia , Polimorfismo de Nucleotídeo Único/genética , Estudos Retrospectivos
16.
Curr Pediatr Rev ; 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37937576

RESUMO

There is evidence that few trace elements in the environment work as hazardous materials in terms of their exposure in the perinatal period, causing autistic spectrum disorder (ASD) in children, and avoiding these exposures in the environment can reduce the number of new cases. This perspective study provides preliminary evidence to consider a few trace elements as culprits for ASD. More studies with larger cohorts are needed, but meanwhile, as per available evidence, exposure to these hazardous materials must be warranted during pregnancy and early stages of life.

17.
J Orthop Case Rep ; 13(10): 163-167, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37885625

RESUMO

Introduction: Tuberculosis (TB) of pubic symphysis is an extremely uncommon condition accounting <1% of all musculoskeletal TB. Further recurrence of TB of symphysis pubis is a rare clinical scenario requiring a high level of suspicion for diagnosing the condition. Recurrence of tuberculosis can occur either be due to relapse of the original infection or reinfection due to exogenous Mycobacterium tuberculosis strain. There have only been nine case reports on TB of the pubic symphysis in the last three decades and only 40 patients were identified in English language medical literature so to the best of our knowledge this is the first case report on the recurrence of TB of pubic symphysis. Case Report: A 26-year-old female patient presented with pain over symphyseal area for 2 months. Laboratory and radiological investigations were suggestive of TB of symphysis pubis. She was started on oral, category I anti-tubercular therapy (ATT) from DOTS center. Patient on improvement in symptoms discontinued taking ATT after 6 months. About 7 months after stopping ATT, she again presented with pain over symphyseal area and difficulty in walking. Laboratory, radiological investigation, and biopsy were obtained to rule out multidrug-resistant (MDR) TB. The patient improved on 12 months' oral daily ATT regime (HRZES2+HRZE4+HRE6). She was followed up for another 1 year with clinical examination and laboratory investigation after stopping ATT. At present, she is asymptomatic with no signs of recurrence after 1 year of completion of treatment. Conclusion: ATT intake should be continued for 12 months for musculoskeletal TB for preventing recurrence. The biopsy needs to be taken from the affected region in recurrence TB to rule out MDR.

18.
J Acquir Immune Defic Syndr ; 92(5): 414-421, 2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-36580636

RESUMO

BACKGROUND: Anemia is linked to neurocognitive impairment (NCI) in people with HIV (PWH), but its impact within specific ability domains, and in diverse populations with HIV, is uncertain. METHODS: Participants included 1339 PWH enrolled in observational HIV cohort studies with a mean of 3 comprehensive neurocognitive assessments over 30 months. Global and domain-specific neurocognitive function were assessed by the global deficit score and domain deficit score (GDS and DDS, respectively) or as GDS-defined or DDS-defined NCI (GDS ≥ 0.5, DDS > 0.5). Time-dependent associations of anemia or red-cell indices with neurocognitive function were evaluated by multivariable regression. RESULTS: The mean age at entry was 43.6 years (85% male, 23.9% Hispanic, 16.7% African ancestry by self-report, and 69.8% virally suppressed). Anemia occurred at entry in 297 (22.2%) and developed subsequently in another 129 (9.6%). Anemia (present in 26.8% of cognitively impaired PWH at entry) and lower hemoglobin were associated with higher (worse) GDS values; the association for anemia persisted after multivariable adjustment and in virally suppressed persons ( P < 0.0001). Anemia was also associated with reduced processing speed, motor function, learning, delayed recall, working memory (all P < 0.01), executive function ( P = 0.021), and verbal fluency ( P = 0.035), and these findings persisted in longitudinal analyses (adjusted P < 0.01 for all domains, except verbal fluency). Higher mean corpuscular volume and mean corpuscular hemoglobin were associated with less impairment in learning and recall (all P < 0.05). CONCLUSIONS: Anemia in diverse and virally suppressed PWH associates with reduced neurocognitive performance in multiple domains, cross-sectionally and over time. The impact of identifying and treating anemia to prevent or slow neurocognitive decline in PWH should be prospectively evaluated.


Assuntos
Anemia , Infecções por HIV , Adulto , Humanos , Masculino , Feminino , Infecções por HIV/complicações , Índices de Eritrócitos , Estudos de Coortes , Anemia/complicações , Função Executiva
19.
Malar J ; 11: 306, 2012 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-22943054

RESUMO

BACKGROUND: Malaria and HIV co-infection adversely impact the outcome of both diseases and previous studies have mostly focused on falciparum malaria. Plasmodium vivax contributes to almost half of the malaria cases in India, but the disease burden of HIV and P. vivax co-infection is unclear. METHODS: HIV-infected subjects (n=460) were randomly selected from the 4,611 individuals seen at a Voluntary Counseling and Testing Center in Chennai, India between Jan 2 to Dec 31 2008. Malaria testing was performed on stored plasma samples by nested PCR using both genus-specific and species-specific primers and immunochromatography-based rapid diagnostic test for detecting antibodies against Plasmodium falciparum and P. vivax. RESULTS: Recent malaria co-infection, defined by the presence of antibodies, was detected in 9.8% (45/460) participants. Plasmodium vivax accounted for majority of the infections (60%) followed by P. falciparum (27%) and mixed infections (13%). Individuals with HIV and malaria co-infection were more likely to be men (p=0.01). Between those with and without malaria, there was no difference in age (p=0.14), CD4+ T-cell counts (p=0.19) or proportion CD4+ T-cell below 200/mL (p=0.51). CONCLUSIONS: Retrospective testing of stored plasma samples for malaria antibodies can facilitate identification of populations with high rates of co-infection, and in this southern India HIV-infected cohort there was a considerable burden of malaria co-infection, predominantly due to P. vivax. However, the rate of P. falciparum infection was more than 6-fold higher among HIV-infected individuals than what would be expected in the general population in the region. Interestingly, individuals co-infected with malaria and HIV were not more likely to be immunosuppressed than individuals with HIV infection alone.


Assuntos
Coinfecção/epidemiologia , Infecções por HIV/epidemiologia , Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Adulto , Idoso , Anticorpos Antiprotozoários/sangue , Feminino , Anticorpos Anti-HIV/sangue , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estudos Soroepidemiológicos , Adulto Jovem
20.
Cureus ; 14(2): e22199, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35308734

RESUMO

Spontaneous spinal epidural hematoma (SSEH) is a serious but infrequent cause of profound neurological compromise of acute onset. It is often an atraumatic occurrence, and in around half of the cases, no etiology is identified. However, several causes such as arteriovenous malformation in the spine, use of anticoagulants in various cardiovascular diseases, and spinal trauma have been incriminated for its development. Here we encountered a case of SSEH following unregulated use of anticoagulants after a mitral valve replacement surgery. The patient had complete paraplegia with bowel and bladder involvement. The case was treated with decompressive laminectomy with regularization of her coagulation profile. Although she presented late to the healthcare center for the treatment, she showed a remarkable neurological improvement with gaining power worth near independent ambulation after one year of follow-up.

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