Category: Nevin Manimala

Biol Sex Differ. 2023 Mar 31;14(1):15. doi: 10.1186/s13293-023-00501-2.

ABSTRACT

BACKGROUND: Staphylococcus aureus (S. aureus) is a pathogen responsible for a wide range of clinical manifestations and potentially fatal conditions. There is a paucity of information on the influence of androgens in the immune response to S. aureus infection. In this study, we evaluated the influence of the hormone 5α-dihydrotestosterone (DHT) on mouse peritoneal macrophages (MPMs) and human peripheral blood monocytes (HPBMs) induced by S. aureus.

METHODS: An in vitro model of MPMs from BALB/c sham males, orchiectomised (OQX) males, and females was used. Cells were inoculated with 10 μL of S. aureus, phage-type 80 or sterile saline (control) for 6 h. The MPMs of OQX males and females were pre-treated with 100 μL of 10^-2 M DHT for 24 h before inoculation with S. aureus. The concentration of the cytokines TNF-α, IL-1α, IL-6, IL-8, and IL-10; total nitrites (NO^-2); and hydrogen peroxide (H₂O₂) were measured in the supernatant of MPM cultures. In addition, the toll-like receptor 2 (TLR2) and nuclear factor kappa B (NF-kB) genes that are involved in immune responses were analysed. For the in vitro model of HPBMs, nine men and nine women of childbearing age were selected and HPBMs were isolated from samples of the volunteers’ peripheral blood. In women, blood was collected during the periovulatory period. The HPBMs were inoculated with S. aureus for 6 h and the supernatant was collected for the analysis of cytokines TNF-α, IL-6, IL-12; and GM-CSF, NO^-2, and H₂O₂. The HPBMs were then removed for the analysis of 84 genes involved in the host’s response to bacterial infections by RT-PCR array. GraphPad was used for statistical analysis with a p value < 0.05.

RESULTS: Our data demonstrated that MPMs from sham males inoculated with S. aureus displayed higher concentrations of inflammatory cytokines and lower concentrations of IL-10, NO^-2, and H₂O₂ when compared with MPMs from OQX males and females. A similar result was observed in the HPBMs of men when compared with those of women. Previous treatment with DHT in women HPBMs increased the production of pro-inflammatory cytokines and decreased the levels of IL-10, NO^-2, and H₂O₂. The analysis of gene expression showed that DHT increased the activity of the TLR2 and NF-kB pathways in both MPMs and HPBMs.

CONCLUSIONS: We found that DHT acts as an inflammatory modulator in the monocyte/macrophage response induced by S. aureus and females exhibit a better immune defence response against this pathogen.

PMID:37004108 | DOI:10.1186/s13293-023-00501-2

Eye Vis (Lond). 2023 Apr 1;10(1):14. doi: 10.1186/s40662-023-00331-8.

ABSTRACT

BACKGROUND: Macular edema (ME) is a major complication of retinal disease with multiple mechanisms involved in its development. This study aimed to investigate the metabolite profile of aqueous humor (AH) in patients with ME of different etiologies and identify potential metabolite biomarkers for early diagnosis of ME.

METHODS: Samples of AH were collected from 60 patients with ME and 20 age- and sex-matched controls and analyzed by liquid chromatography-mass spectrometry (LC/MS)-based metabolomics. A series of univariate and multivariate statistical analyses were performed to identify differential metabolites and enriched metabolite pathways.

RESULTS: The metabolic profile of AH differed significantly between ME patients and healthy controls, and differentially expressed metabolites were identified. Pathway analysis revealed that these differentially expressed metabolites are mainly involved in lipid metabolism and amino acid metabolism. Moreover, significant differences were identified in the metabolic composition of AH from patients with ME due to different retinal diseases including age-related macular degeneration (AMD-ME), diabetic retinopathy (DME) and branch retinal vein occlusion (BRVO-ME). In total, 39 and 79 etiology-specific altered metabolites were identified for AMD-ME and DME, respectively. Finally, an AH-derived machine learning-based diagnostic model was developed and successfully validated in the test cohort with an area under the receiver operating characteristic (ROC) curve of 0.79 for AMD-ME, 0.94 for DME and 0.77 for BRVO-ME.

CONCLUSIONS: Our study illustrates the potential underlying metabolic basis of AH of different etiologies across ME populations. We also identify AH-derived metabolite biomarkers that may improve the differential diagnosis and treatment stratification of ME patients with different etiologies.

PMID:37004107 | DOI:10.1186/s40662-023-00331-8

AIDS Res Ther. 2023 Mar 31;20(1):20. doi: 10.1186/s12981-023-00514-2.

ABSTRACT

BACKGROUND: We investigated the association between CYP2B6 polymorphisms and efavirenz drug resistance among women living with HIV who started on antiretroviral therapy during pregnancy and with high viremia during post-partum.

METHODS: This was a cross-sectional study of women with viral loads greater than 1000 copies/ml who were at least 6 weeks postpartum. Sanger sequencing was used to detect resistant mutations, as well as host genotyping, and efavirenz resistance was compared among the metabolizer genotypes.

RESULTS: Over the course of one year (July 2017-July 2018), 322 women were screened, with 110 (34.2%) having viral loads of 1000 copies/ml and 62 having whole blood available for genotyping. Fifty-nine of these women had both viral resistance and human host genotypic results. Efavirenz resistance according to metabolizer genotype was; 47% in slow, 34% in extensive and 28% in intermediate metabolizers, but the difference was not statistically significant due to the small sample size.

CONCLUSIONS: There was no statistically significant difference in EFV resistance between EFV metabolizer genotypes in women who started antiretroviral therapy during pregnancy and had high viremia in the postpartum period. However, a numerical trend was discovered, which calls for confirmation in a large, well-designed, statistically powered study.

PMID:37004096 | DOI:10.1186/s12981-023-00514-2

Arthroplasty. 2023 Apr 2;5(1):18. doi: 10.1186/s42836-023-00175-6.

ABSTRACT

INTRODUCTION: Primary total knee arthroplasty (TKA) is a preferred treatment for end-stage knee osteoarthritis. In the setting of a failed TKA, revision total knee arthroplasty (rTKA) acts as a salvage procedure and carries a higher risk compared to primary TKA. Given increased interest in postoperative outcomes from these procedures, a thorough understanding of the demographics, comorbidities, and inpatient outcomes is warranted. This study aimed to report the epidemiological data of demographics, comorbidity profiles and outcomes of patients undergoing TKA and rTKA.

METHODS: A retrospective review of NIS registry discharge data from 2006 to 2015 third quarter was performed. This study included adults aged 40 and older who underwent TKA or rTKA. A total of 5,901,057 TKA patients and 465,968 rTKA patients were included in this study. Simple descriptive statistics were used to present variables on demographics, medical comorbidities, and postoperative complications.

RESULTS: A total of 5,901,057 TKA and 465,968 rTKA discharges were included in this study, with an average age of 66.30 and 66.56 years, and the major payor being Medicare, accounting for 55.34% and 59.88% of TKA and rTKA cases, respectively. Infection (24.62%) was the most frequent reason for rTKA, and was followed by mechanical complications (18.62%) and dislocation (7.67%). The most common medical comorbidities for both groups were hypertension, obesity, and diabetes. All types of inpatient complications were reported in 22.21% TKA and 28.78% of rTKA cases. Postoperative anemia was the most common complication in both groups (20.34% vs. 25.05%).

CONCLUSIONS: Our data demonstrated a 41.9% increase in patients receiving TKA and 28.8% increase in rTKA from the years 2006 to 2014. The data showed a 22.21% and a 28.78% “complication” rate with TKA and rTKA, with postoperative anemia being the most common complication. The top 3 medical comorbidities were hypertension, obesity, and diabetes for both groups and with increased focus on perioperative optimization, future analyses into preoperative medical optimization, and improved primary arthroplasty protocol may result in improved postoperative outcomes.

PMID:37004093 | DOI:10.1186/s42836-023-00175-6

Retrovirology. 2023 Mar 31;20(1):3. doi: 10.1186/s12977-023-00618-7.

ABSTRACT

BACKGROUND: Nef performs multiple cellular activities that enhance HIV-1 pathogenesis. The role of Nef-mediated down-regulation of the host restriction factor SERINC5 in HIV-1 pathogenesis is not well-defined. We aimed to investigate if SERINC5 down-regulation activity contributes to HIV-1 subtype C disease progression, to assess the relative contribution of this activity to overall Nef function, and to identify amino acids required for optimal activity. We measured the SERINC5 down-regulation activity of 106 subtype C Nef clones, isolated from individuals in early infection, for which the Nef activities of CD4 and HLA-I down-regulation as well as alteration of TCR signalling were previously measured. The relationship between SERINC5 down-regulation and markers of disease progression, and the relative contribution of SERINC5 down-regulation to a Nef fitness model-derived E value (a proxy for overall Nef fitness in vivo), were assessed.

RESULTS: No overall relationship was found between SERINC5 down-regulation and viral load set point (p = 0.28) or rate of CD4⁺ T cell decline (p = 0.45). CD4 down-regulation (p = 0.02) and SERINC5 down-regulation (p = 0.003) were significant determinants of E values in univariate analyses, with the greatest relative contribution for SERINC5 down-regulation, and only SERINC5 down-regulation remained significant in the multivariate analysis (p = 0.003). Using a codon-by-codon analysis, several amino acids were significantly associated with increased (10I, 11V, 38D, 51T, 65D, 101V, 188H and, 191H) or decreased (10K, 38E, 65E, 135F, 173T, 176T and, 191R) SERINC5 down-regulation activity. Site-directed mutagenesis experiments of selected mutants confirmed a substantial reduction in SERINC5 down-regulation activity associated with the mutation 173T, while mutations 10K, 135F, and 176T were associated with more modest reductions in activity that were not statistically significant.

CONCLUSIONS: These results suggest that SERINC5 down-regulation is a significant contributor to overall Nef function and identify potential genetic determinants of this Nef function that may have relevance for vaccines or therapeutics.

PMID:37004071 | DOI:10.1186/s12977-023-00618-7

J Ethnobiol Ethnomed. 2023 Mar 31;19(1):9. doi: 10.1186/s13002-023-00581-9.

ABSTRACT

BACKGROUND: The Patrak Valley is home to communities, which have been inextricably linked with nature for generations, and local plant knowledge (LPK) represents an important part of their local cultural diversity. In general, globalization has come at the expense of local plant knowledge among several mountain societies, and therefore the current investigation has been undertaken to record the (possibly) last remaining wild food plant/mushroom foraging practices among Pathans, Kohistanis, and Gujjars living in the highlands of the Hindukush, North Pakistan.

METHODS: Data on the uses of wild food plants and mushrooms (WFPs) were collected through 120 semi-structured interviews. The data were cross-culturally compared among the three linguistic groups. Venn diagrams were used to visualize the comparative analysis. To determine the patterns of similarities in plant use among the different ethnic groups, we used the Jaccard similarity index (JI). The recorded data were also compared with the existing Pakistani food ethnobotanical literature.

RESULTS: A total of 68 WFPs were recorded, the majority of which were used as raw snacks and as cooked vegetables. Fruit was the most frequently reported plant part among the three researched groups. Cross-cultural comparison revealed that 37% of the used plants were commonly shared by the three studied groups. Pathans have retained rich knowledge on WFPs, and they show a comparatively closer affinity with Kohistanis is the use of WFPs compared to Gujjars. While we observed some idiosyncrasies for each of the researched groups, the distinctive plant uses among Gujjars provide insight into their food ecology, their particular human-ecological system centered on mobile pastoralism and their limited exchanges of local food/ecological knowledge due to endogamic patterns. A literature survey revealed some novel or little-known ingredients within Pakistani food ethnobotany/ethnomycology, such as Aesculus indica, Agaricus campestris, Apteranthes tuberculata, Duchesnea indica, Equisetum arvense, Eremurus himalaicus, Isodon rugosus, Morella esculenta, Sophora mollis, and Drimia indica.

CONCLUSION: The researched communities have retained important plant knowledge which could be implemented through future development programs considering that most of these traditional foraging practices fulfill environmental and social sustainability standards. Further field studies are required to thoroughly investigate the patterns of foraging among highland pastoral societies in other parts of the Hindukush region and especially their potential for the ongoing ecological transition.

PMID:37004043 | DOI:10.1186/s13002-023-00581-9

World J Surg Oncol. 2023 Mar 31;21(1):119. doi: 10.1186/s12957-023-03003-y.

ABSTRACT

BACKGROUND/OBJECTIVES: To evaluate perioperative safety and outcome of parenchyma-preserving pancreatectomy and risk factors of metastasis and recurrence for patients with solid pseudopapillary neoplasm (SPN).

METHODS: Demographic data, operative and pathological parameter, follow-up data of patients with SPN undergoing their first operation were collected in our single center from May 2016 to October 2021 and compared between regular pancreatectomy group and parenchyma-preserving surgery group. Risk factors for metastasis and recurrence were investigated.

RESULTS: A total of 194 patients were included, 154 of whom were female and the average age of all patients was 33 years old. Most patients were asymptomatic, with the most common complaint being abdominal pain or discomfort. Of them, 62 patients underwent parenchyma-preserving pancreatectomy including middle segment pancreatectomy and enucleation, and 132 patients underwent regular pancreatectomy including pancreaticoduodenectomy, distal pancreatectomy and total pancreatectomy. Patients in the parenchyma-preserving surgery group had a shorter duration of operation, less intraoperative bleeding, and decreased risk of combined organ removal and blood transfusion, with no statistical significance yet. The two groups exhibited a similar incidence of postoperative complications including grade B and C pancreatic fistula, delayed gastric emptying, postoperative pancreatic hemorrhage, and other complications, as well as radiological intervention, relaparotomy and the length of postoperative hospital stay. There were no perioperative deaths. All the patients, except 18 of those who discontinued follow-up, were alive with a median follow-up time of 31 months. Three patients in the regular pancreatectomy group were observed to have liver metastasis, and no metastasis was observed in the parenchyma-preserving surgery group. Significant risk factors for tumor metastasis and recurrence were tumor size, angioinvasion, and nerve infiltration.

CONCLUSIONS: Parenchyma-preserving surgery did not significantly increase the frequency of perioperative complications or recurrence and might be preferable if comprehensive conditions allow.

PMID:37004027 | DOI:10.1186/s12957-023-03003-y

BMC Musculoskelet Disord. 2023 Mar 31;24(1):249. doi: 10.1186/s12891-023-06296-y.

ABSTRACT

OBJECTIVES: The aim of this literature review was to synthesise and report current practice in evaluation and reporting of scar outcomes in hand and wrist clinical research.

METHODS: A systematic search from inception to 2022 was conducted using three electronic databases. English language randomized controlled trials and observational cohort studies reporting standardised scar outcome measures and/or scar symptoms, appearance, impairment, function, or mental health outcomes in patients with hand and wrist scars were included. Two independent reviewers determined study eligibility and performed data extraction of a priori identified scar outcome domains. Data analysis included descriptive statistics and identification of discordance in taxonomy.

RESULTS: Fifty-nine studies were included. Elective surgery cohorts were the most frequently included clinical population (n = 28; 47%) followed by burns (n = 16; 27%). Six different standardised scar outcome measures were reported by 25% of studies however only 7% of studies utilised a patient-reported measure. Scar symptoms were the most frequently reported outcome domain (81%); but taxonomy was incongruous, constructs lacked working definitions required for generalisability and outcome measurement was variable and unreported. Nineteen different measures of scar appearance and structure were reported by 30 (51%) of studies however only nine (23%) were patient-reported. Seven different hand function PROMs were reported by 25 (43%) studies. Person-centred domains including scar acceptability (12%), mental health impact (5%), and social participation (4%) were rarely reported.

CONCLUSIONS: This review highlights that evaluation and reporting of hand and wrist scar outcomes is not standardised, assessment methods and measures are under-reported and there is discordance in taxonomy. Evaluation is not person-centred, rather it is dependent on clinician assessment. Domains including scar acceptability, mental health, and social participation are rarely addressed. A stakeholder consensus derived hand and wrist scar core outcome measurement set will promote standardisation and underpin improvements in clinical research quality, transparency, and rigour.

PMID:37004025 | DOI:10.1186/s12891-023-06296-y

BMC Public Health. 2023 Mar 31;23(1):616. doi: 10.1186/s12889-022-14907-x.

ABSTRACT

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality worldwide and in Colombia. The analysis of CVD mortality has been mainly relied on individual factors and rates, but occurrence is also related to contextual conditions. Understanding the distribution of CVD in a region will contribute to implement more focused-preventive and care interventions.

METHODS: Using the national mortality register established by the Department of National Statistics, standardized rates and spatial distribution of CVD mortality were estimated for Cali, Colombia, between 2010-2017. Global and local spatial aggregation was assessed using the Geary’s C test and for each district standardized mortality ratios smoothed by the Bayesian empirical were estimated.

RESULTS: Over the period, CVD was the main cause of mortality with 28,804 deaths accounting for 23,8% of total deaths. The global CVD mortality rate varied from 235.9 to 257.4 per 100.000 habitants, with an average increase of 9.1% in the percentage change. The main cause of mortality were hypertensive diseases following by ischemic heart diseases and stroke. The standardized mortality ratios smoothed by the Bayesian empirical method showed that the districts 7, 13, 14, 15 and 16 located at the eastern area with the lowest socio-economic strata and the district 22 at the south of the city with the highest socio-economic strata had the high risks of CVD mortality. All these areas were at the boundary of the city. The the lowest risk was observed in districts 1 and 2 at the northwest area with the upper socio-economic strata. Over the study period, a spatial autocorrelation was found in the districts 1,9 10, 11, 12, 13, 14, 15, 19, and 21 by using the Geary’s C test. The highest significant spatial association was found in the districts 1 and 21.

CONCLUSION: Of 22 districts in Cali, the highest risk of CVD mortality was found in three at the lowest and one in the upper socio-economic strata between 2013 and 2017. Over the period a global spatial aggregation was identified due mainly to districts peripherical located suggesting that there could be contextual conditions influencing the risk. Therefore, there is a need for considering local conditions to prevent CVD mortality.

PMID:37004013 | DOI:10.1186/s12889-022-14907-x

BMC Infect Dis. 2023 Mar 31;23(1):196. doi: 10.1186/s12879-023-08177-0.

ABSTRACT

BACKGROUND: Acute invasive fungal rhinosinusitis (AIFRS) is a fatal infection associated with high morbidity and mortality. Although it is a rare disease, upsurge of AIFRS was noticed during the second wave of COVID-19 disease. Early diagnosis and management is the cornerstone for good outcomes. However, management of AIFRS is challengeable especially in developing countries due to limited resources and high prices of antifungal agents. No previous studies have been conducted to evaluate the outcomes of management of AIFRS in Syria. The purpose of this study is to report the results of management of AIFRS with low doses of liposomal amphotericin B in our tertiary hospital in Syria.

METHODS: The outcomes of management of AIFRS cases were followed through a prospective observational study between January 2021 and July 2022. The required medical data were collected for each individual. Three-month mortality rate was studied. SPSS v.26 was used to perform the statistical analysis. Pearson Chi-square test was used to study the associations between different variables and mortality. Survival curves were plotted by the Kaplan-Meier to compare the survival probability. Log Rank (Mantel-Cox) test and Cox regression were conducted to evaluate the factors affecting survival within the follow up period.

RESULTS: Of 70 cases, 36 (51.4%) were males and 34 (48.6%) were females. The mean age of patients was 52.5 years old. The most common underlying risk factor was diabetes mellitus (84.3%). The used dose of liposomal amphotericin B ranged between 2-3 mg/kg per day. The overall 3-month mortality rate was 35.7%. Significant association was found between survival and the following variables: Age, orbital involvement, stage, and comorbidity.

CONCLUSION: The overall mortality rate was close to other studies. However, survival rate was worse than comparable studies in selected cases of AIFRS (older ages, involved orbits, advanced stages, and chronic immunodeficiency). Therefore, low doses of liposomal amphotericin B could be less effective in such cases and high doses are recommended.

PMID:37004006 | DOI:10.1186/s12879-023-08177-0