Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 45
Filtrar
1.
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.

2.
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.

3.
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 , Humanos , Feminino , Masculino , eIF-2 Quinase/genética , Adulto , Infecções por HIV/genética , Infecções por HIV/complicações , Infecções por HIV/psicologia , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Estudos Retrospectivos , Estudos de Coortes , Disfunção Cognitiva/genética
4.
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
5.
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
6.
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.

7.
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.

8.
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
9.
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
10.
J Family Med Prim Care ; 11(4): 1443-1449, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35516720

RESUMO

Background: The health-related problems of the tribal population depend on their ecology and culture. Often the tribal people do not utilize the medical and preventive health services available to them. Health problems in tribal groups need special attention because many tribal communities are backward. The current study was planned to determine the healthcare-seeking behavior of the tribal population in India. Method: A descriptive, cross-sectional study, conducted by interviewing key respondents of each participating family. Result: Two-thirds of the key respondents were literate and half (53.8%) of the total households in the three villages had a per capita monthly income between Rupees 500-1499. More than half (57%) of all respondents preferred government institutions for moderate illness, and the rest equally opted for private practitioners and quacks. However, for emergencies, dog bites, and snake bites, all key respondents in the three study villages unanimously preferred government institutions. A significant population (38.5%) got their children delivered at home. The majority of illiterate respondents (86.1%) preferred government institutions for health care of under-five children, while 60% of literates expressed a similar view. The choice of government institutions as a source of health care was increasingly favored with decreasing per capita monthly household income. Conclusion: Traditional healers are no longer preferred among the tribal population but they are reluctant to avail them because of the loss of valuable time. Home delivery is still prevalent. With improving socioeconomic status, people are going further away from government services as private practitioners, and quacks take less time.

11.
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.

12.
Toxicon ; 208: 62-77, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35104534

RESUMO

Trichothecenes (TCNs) are the mycotoxins produced by many fungal species such as Fusarium, Myrothecium, and Stachybotrys and pose a considerable health risk. Based on their characteristic functional moieties, they are divided into four categories: Type A (T-2, HT-2, diacetoxyscirpenol (DAS), harzianum A, neosolaniol (NEO) and trichodermin), Type B (deoxynivalenol (DON), nivalenol (NIV), trichothecin and fusarenon X), Type C (crotocin) and Type D (satratoxin G & H, roridin A and verrucarin A) with types A and B being the most substantial. TCNs cause growth retardation in eukaryotes, suppress seedling growth or regeneration in plants and could be a reason for animal reproductive failure. Due to the increased frequency of occurrence and widespread distribution of TCNs in food and feed, knowledge of their sources of occurrence is essential to strategise their control and management. Hence, this review provides an overview of various types and sources of TCNs, the associated biosynthetic pathways and genes responsible for production in food and feed. Further, various processing and environmental effects on TCNs production, detection techniques and management strategies are also briefly outlined.


Assuntos
Fusarium , Micotoxinas , Tricotecenos , Animais , Contaminação de Alimentos/análise , Humanos , Micotoxinas/análise , Micotoxinas/toxicidade , Tricotecenos/análise , Tricotecenos/toxicidade
13.
Chemosphere ; 295: 133852, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35122812

RESUMO

The present study deals with the dual problem of municipal solid waste and lignocellulosic waste in which authors tried to use these two waste materials as clean and renewable energy source. In the present study, anaerobic digestion of organic fraction of municipal solid waste and lignocellulosic waste in varying combinations was carried out. Five-set of experiments (S1, S2, S3, S4, and S5) under mesophilic conditions were conducted in batch reactors. From all the combinations, reactor S3 (organic fraction of municipal solid waste: lignocellulosic waste, 1:1 ratio) was observed to be the best combination producing 70.09 ml concentration of methane out of 78.76 ml of biogas as compared to all other combinations. The increase in methane production rate was observed by 53.67% due to the addition of lignocellulosic waste. The decline in methane production at the end of the 50th day was observed due to a fall in pH, which created acidic conditions, thus inhibiting the conversion process. It was found that the mesophilic condition acted as a governing factor in the process of digestion.


Assuntos
Eliminação de Resíduos , Resíduos Sólidos , Anaerobiose , Biocombustíveis/análise , Reatores Biológicos , Digestão , Lignina , Metano , Resíduos Sólidos/análise
15.
J Orthop Case Rep ; 11(4): 6-9, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34327155

RESUMO

INTRODUCTION: Aneurysmal bone cysts (ABC's) are expansile, tumour-like vascular lesion. They are more commonly seen in the metaphyseal region of long bones. They are benign lesion although malignant transformation has been reported. Usually presents in the first three decades of life. Common presentation is pain, swelling, or fracture. Proximal femur with ABC's is a rare entity and with physeal extension is even sparse. CASE REPORT: A 13- year-. old female presented in the orthopaedic emergency with complaints of pain in the right hip region following a trivial fall. Following trauma, the patient was unable to stand or walk. On examination, there was tenderness in Scarpa's triangle, straight leg raise test was not possible and limb was in external rotation. Plain radiography revealed an inter-trochanteric fracture with cystic lesion in the proximal femur extending till until epiphysis. MRI of the proximal femur showed an air fluid level with septations and soft- tissue oedema suggestive of aneurysmal bone cyst ABC's.The patient was managed by intra-lesional curettage with fibular strut grafting along with cancellous bone graft and fixation by Uni-planar external fixator. CONCLUSION: Pathological Fractures fractures of proximal femur management is are a challenge for an orthopaedic surgeon due to its location and biomechanical factors. Treatment of proximal femur ABC's should be case dependent. In our opinion, aneursymal bone cyst of the proximal femur with physeal extension can be managed by external fixation along with extensive curettage and bone graft.

16.
J Orthop Case Rep ; 11(1): 104-107, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34141654

RESUMO

INTRODUCTION: Sleeve fracture (SF) represents an unusual type of patellar fracture and has been reported mainly in children or adolescents. Superior pole fracture in adults is a very rare occurrence because the enthesis of the adult patella is more resilient to avulsion injury as compared to an immature pediatric skeleton. Due to the rarity of these fractures in adults and vague radiographic findings, the chances of missing the fracture are very high. CASE REPORT: An 18-year-old boy presented to our outpatient department with a history of fall while trying to jump across a wall 6 months ago. At the time of presentation, the patient mainly complained of loss of active extension of the knee in the sitting position and a palpable gap over the upper part of the patella. After radiographic evaluation, a diagnosis of SF was made. The patient was managed surgically, and thereafter, early rehabilitation was done. After 10 weeks post-surgery, the patient was free from any pain, had a full range of motion, and was able to walk without support. CONCLUSION: Adults presenting with acute injury to knee with limitation of extension and palpable gap over the superior pole of the patella, a differential diagnosis of SF must be suspected and should be ruled out by clinical examination and relevant investigations.

17.
Neurology ; 97(2): e156-e165, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-33947785

RESUMO

OBJECTIVE: The primary objective of this study was to evaluate the correlation of large mitochondrial DNA (mtDNA) deletions in skin samples of people with HIV (PWH) with measures of neuropathy and prior exposure to therapy. We hypothesized that deletions would be associated with neuropathy. As secondary objectives, we determined the correlation of deletion burden with demographic data and neuropathy measures. METHODS: In this retrospective cohort study, we measured the accumulation of large mtDNA deletions in skin biopsies from PWH recruited as part of the AIDS Clinical Trials Group (ACTG). Our cohort includes individuals with and without sensory neuropathy, as well as individuals with normal or abnormal skin biopsies. Skin biopsies, sural and peroneal nerve conduction studies, total neuropathy score, and deletion burden scores were measured, along with baseline demographic data such as age, CD4+ cell count, viral counts, and prior nucleoside reverse transcriptase inhibitor exposures. RESULTS: Sixty-seven PWH were enrolled in the study. The mean age of the cohort (n = 67) was 44 years (SD 6.8, range 32-65 years), and 9 participants were female. The mean CD4+ T-cell count was 168 cells/mm3 (SD 97 cells/mm3, range 1-416 cells/mm3) and mean viral load was 51,129 copies/mL (SD 114,586 copies/mL, range 147-657,775 copies/mL). We determined that there was a correlation between the total mtDNA deletion and intraepidermal nerve fiber density (IENFD) (r = -0.344, p = 0.04) and sural nerve amplitude (r = -0.359, p = 0.004). CONCLUSIONS: Both IENFD and sural nerve amplitude statistically correlate with mitochondrial mutation burden in PWH, specifically in those with HIV-associated sensory neuropathy as assessed by skin biopsy.


Assuntos
DNA Mitocondrial/genética , Infecções por HIV/genética , Mutação , Doenças do Sistema Nervoso Periférico/genética , Neuropatias Fibulares/genética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/fisiopatologia , Neuropatias Fibulares/fisiopatologia , Estudos Retrospectivos , Pele/patologia , Pele/fisiopatologia , Nervo Sural/fisiopatologia
18.
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
19.
J Family Med Prim Care ; 10(12): 4502-4508, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35280608

RESUMO

Introduction: The aim of this study was to compare the effect of a steroid injection with conservative therapy (CT) versus CT alone on pain, functional limitations and the cross-sectional area (CSA) of the radial nerve (RN) in patients with lateral epicondylitis (LE). Methods: In this clinical trial, seventy subjects in the age group of 30-60 years with a clinical diagnosis of LE were recruited. Patients received an ultrasound-guided steroid injection and CT (Group A, n = 35) or CT alone (Group B, n = 35). Pain intensity (numeric pain rating scale), functional limitations (Quick Disabilities of the Arm, Shoulder, and Hand questionnaire) and the CSA of RN (mm2) using ultrasound were assessed at baseline, 4 and 12 weeks. Results: There was a significant difference in pain intensity (P < 0.05) at 4 weeks in favour of Group A but not at 12 weeks. A statistically significant difference was not present favouring either group concerning disability at both the follow-ups. The difference in CSA of the RN at the affected side in both groups A and B was not statistically significant at either the spiral groove or the antecubital fossa at baseline or the subsequent follow-ups. Conclusions: The CT with a steroid injection proved to be more efficacious in the short term concerning pain intensity and functional limitations. The RN thickness is not increased in patients with LE, thereby refuting its role to some extent in the pathogenesis of LE.

20.
J Acquir Immune Defic Syndr ; 86(1): 91-97, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33021552

RESUMO

BACKGROUND: HIV and malaria are associated with immunological perturbations and neurocognitive disorders even when asymptomatic. However, the effect of asymptomatic malaria (AM) in HIV-infected adults on neurocognitive impairment (NCI) is not well understood. This study investigated the biomarkers of systemic inflammation and neurocognition in dually infected Nigerian adults. METHODS: We assessed the HIV and AM status of 269 adults and measured their global and domain-specific neurocognition and depression using standardized measures. Blood levels of sCD14 and sCD163 were also measured. RESULTS: The mean age of the participants (n = 269) was 33 years, 62% were women, and AM among HIV+ and HIV- was similar (36% versus 37%). NCI was found in 23% (62/269) of participants. HIV+/AM+ had a higher prevalence of impaired learning and executive functions and were more depressed than HIV-/AM- or HIV+/AM-. HIV+ with CD4 T-cell counts ≤200/µL were more impaired in the learning domain than those with >200/µL. HIV+/AM+ group had higher levels of sCD14 compared to the other 3 groups and higher levels of sCD163 than the HIV-/AM- group. Higher levels of sCD14 and sCD163 were each associated with NCI. The sCD163 (log10) levels were higher for those with 1+ versus 2+ parasitemia level. CONCLUSIONS: HIV and AM coinfection was associated with an increased risk of reduced learning and executive functions, and elevated systemic inflammation. Mood was more depressed in HIV patients with than those without AM. The mechanisms and long-term effects on neurocognition and depression among HIV+/AM+ individuals should be studied because this coinfection is common globally.


Assuntos
Infecções Assintomáticas , Coinfecção/epidemiologia , Infecções por HIV/epidemiologia , Inflamação/complicações , Malária/epidemiologia , Adulto , Infecções Assintomáticas/epidemiologia , Biomarcadores/sangue , Cognição , Coinfecção/complicações , Estudos Transversais , Feminino , Infecções por HIV/complicações , Humanos , Receptores de Lipopolissacarídeos/sangue , Malária/complicações , Malária/diagnóstico , Masculino , Nigéria/epidemiologia , Prevalência , Estudos Prospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA