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Nevin Manimala Statistics

Immuno-hematological parameters among adult HIV patients before and after initiation of Dolutegravir based antiretroviral therapy, Addis Ababa, Ethiopia

PLoS One. 2024 Oct 31;19(10):e0310239. doi: 10.1371/journal.pone.0310239. eCollection 2024.

ABSTRACT

BACKGROUND: Immuno-hematological abnormalities are common among HIV infected individuals as well as patients with highly active antiretroviral therapy (HAART). However, the immuno-hematological outcome of Dolutegravir based antiretroviral therapy (ART) usage is not well investigated.

OBJECTIVES: To assess hematological and immunological parameters among adult HIV patients before and after initiation of Dolutegravir based ART regimen at St. Peter Specialized Hospital, Addis Ababa, Ethiopia.

METHODS: A cross-sectional study was conducted from May to July 2021 at St. Peter Specialized Hospital among adult HIV patients. A total of 422 HIV patients on Dolutegravir based ART (combination of Dolutegravir/lamivudine/tenofovir disoproxil fumarate (DTG/3TC/TDF)) for a minimum of 3 months were selected using convenient sampling methods. Socio-demographic as well as clinical data of the participants was obtained using pre-tested structured questionnaires and a review of medical records. Hematological parameters such as CBC was obtained using Beckman coulter automated hematology analyzer and immunological parameters such as CD4 count were determined using BD FACS presto. Statistical analysis of the data was done using SPSS version 21. Paired t-test was used to compare dependent variables before and after initiation of the new HAART and binary logistic regression was used to determine predictors of immuno-hematological abnormalities. P-value < 0.05 was considered as statistically significant.

RESULTS: Of 422 adult HIV patients, about 273(64.7%) were females. The mean age of study participants was 42.2 years (±10.4SD). The mean white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin (Hb), platelet distribution width (PDW), CD4 count, as well as lymphocyte percentage, neutrophil percentage, and platelet counts (PLT) were increased significantly(P<0.05) after 3 months of the Dolutegravir based therapy. While, red cell distribution width (RDW) and mean cell hemoglobin (MCH) were decreased (P<0.05) after the treatment. Other hematological parameters such as mean cell volume (MCV), hematocrit (HCT), mean cell hemoglobin concentration (MCHC), mean platelet volume (MPV) and platelet distribution width (PDW) showed no significant change. On the other hand, the most common hematological abnormalities identified after the new HAART were anemia (12.1%); followed by Leucopenia (11.3%), neutropenia (6%), and thrombocytopenia (4%). Anemia was associated with female sex (AOR = 7.8, 95% CI: 1.9-32.2, P<0.005) and WHO clinical stage III/IV (AOR = 16, 95% CI: 10.63-66.46, P<0.01).

CONCLUSION: There was a significant change in certain immuno-hematological parameters such as WBC count, RBC count, PLT count, Hb, PDW, CD4 count, lymphocyte and neutrophil percentage after initiation of the Dolutegravir based therapy. Anemia was the most common hematological abnormality. Further studies are required to fully comprehend the outcome of the new treatment regimen on immuno-hematological parameters.

PMID:39480901 | DOI:10.1371/journal.pone.0310239

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Nevin Manimala Statistics

Early expression of osteopontin glycoprotein on the ocular surface and in tear fluid contributes to ocular surface diseases in type 2 diabetic mice

PLoS One. 2024 Oct 31;19(10):e0313027. doi: 10.1371/journal.pone.0313027. eCollection 2024.

ABSTRACT

PURPOSE: Osteopontin (OPN) is a glycosylated, secreted phosphoprotein known to be elevated in both human and mouse retinas during various stages of diabetic retinopathy. However, its specific roles in modulating ocular surface dynamics and immune responses in diabetes remain unexplored. This study aims to investigate the role of OPN in the development of ocular surface disease (OSD) in type 2 diabetic (T2D) mice.

METHODS: Three- to four-week-old C57BL/6 wild-type (WT) and OPN-knockout (OPN-/-) mice were fed a high-fat diet (HFD) and were rendered diabetic by streptozotocin (STZ; 40 mg/kg body weight) in citrate buffer (vehicle); non-diabetic controls were injected with vehicle alone. Diabetes was confirmed if blood glucose levels were >200 mg/dL, measured 1-2 weeks post-STZ injection. Control, age- and sex-matched db/db diabetic mice fed a standard chow diet were also included in this study. Ocular surface inflammation was assessed using ELISA to quantify inflammatory cytokine proteins and wheat germ agglutinin (WGA) staining was utilized to highlight corneal surface irregularities. Clinical signs were evaluated by corneal fluorescein staining, tear production measurements, and tear sodium (Na+) concentration assessments. These evaluations were conducted 4, 6, 8 and 16-weeks post-diabetes onset in WT and OPN-/- mice and were compared to those obtained in non-diabetic controls. Statistical analysis was performed using a two-way ANOVA, with significance set at P < 0.05.

RESULTS: Both WT and OPN-/- mice developed T2D within 4 and 8 weeks, respectively, following HFD + STZ treatment. Corneal OPN levels in WT diabetic mice increased ~2-fold at 2 weeks and ~4-fold at 16 weeks compared to non-diabetic controls, with similar elevations observed in their tear fluid. Diabetic db/db mice also exhibited elevated OPN levels in the blood and ocular surface, which persisted as diabetes progressed. Enhanced fluorescein staining, indicating corneal irregularities, appeared in WT mice at 8 weeks and in OPN-/- mice at 10 weeks post-T2D induction. Additionally, WGA staining showed a significant reduction in fluorescence intensity in WT mice treated with HFD and STZ, confirming corneal surface irregularities that were delayed in OPN-/- mice. Elevated tear sodium concentration was observed in both WT and OPN-/- diabetic mice without affecting tear production rates. Notably, OPN levels increased early, at week 2, following HFD and STZ treatment, preceding changes in interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and matrix metalloproteinase-9 (MMP-9). Upregulation of IL-6 became apparent at 6 weeks in WT mice and was delayed until 10 weeks in OPN-/- mice post-T2D induction.

CONCLUSIONS: Elevated OPN levels were detected early post-T2D induction in diabetic WT and db/db mice corneas without initial subclinical changes. This early increase in OPN precedes other proinflammatory cytokines associated with eventual ocular surface inflammation as diabetes progresses. Persistence of OPN also correlated with clinical signs such as increased corneal surface irregularities and elevated tear Na+ concentration. Future research will explore OPN’s role as a biomarker in ocular surface disease (OSD), including dry eye disease (DED), and investigate its impact on inflammatory processes and other mechanistic pathways in diabetic ocular complications.

PMID:39480896 | DOI:10.1371/journal.pone.0313027

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Nevin Manimala Statistics

Alcohol outlet density and adolescent drinking behaviors in Thailand, 2007-2017: A spatiotemporal mixed model analysis

PLoS One. 2024 Oct 31;19(10):e0308184. doi: 10.1371/journal.pone.0308184. eCollection 2024.

ABSTRACT

This study aimed to explore the relationship between alcohol outlet density and the proportion of alcohol consumption among Thai adolescents. We utilized the alcohol consumption data from the 2007, 2011, and 2017 Tobacco and Alcohol Consumption Survey in Thailand. We analyzed the relationships between alcohol sales license figures and consumption behavior using a spatiotemporal mixed model. Our data had two levels. The upper (provincial) level featured alcohol sales license density (spatial effect), the years of survey (temporal effect), and the social deprivation index. The lower (individual) level included the demographic data of the adolescents. A total of 9,566 Thai adolescents participated in this study, based on surveys conducted in 2007 (n = 4,731), 2011 (n = 3,466), and 2017 (n = 1,369). The density of alcohol sales licenses increased the odds for the one-year current drinker category (odds ratio [OR] = 1.08, 95% confidence interval [CI], 1.04-1.45), especially in male adolescents (OR = 1.09, 95% CI, 1.04-1.14). Furthermore, it increased the odds for the heavy episodic drinker category for female adolescents (OR = 1.23, 95% CI, 1.05-1.44). Increased alcohol sales licenses are associated with higher alcohol consumption among Thai adolescents. This highlights the need for government organizations to develop and apply strategies to reduce the number of licenses for the sale of alcohol.

PMID:39480894 | DOI:10.1371/journal.pone.0308184

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A change in circulating chikungunya virus variant impacts Aedes aegypti vector competence and spatiotemporal distribution of disease in Malaysia

PLoS Negl Trop Dis. 2024 Oct 31;18(10):e0012632. doi: 10.1371/journal.pntd.0012632. Online ahead of print.

ABSTRACT

BACKGROUND: In 2008-2010, Malaysia experienced a nationwide chikungunya virus (CHIKV) outbreak caused by the Indian Ocean lineage E1-226V (valine) variant, adapted to Aedes albopictus. In 2017-2022, transition to an E1-226A (alanine) variant occurred. Ae. albopictus prevails in rural areas, where most cases occurred during the E1-226V outbreak, while Ae. aegypti dominates urban areas. The shift in circulating CHIKV variants from E1-226V to E1-226A (2009-2022) was hypothesized to result in a transition from rural to urban CHIKV distribution, driven by differences in Ae. aegypti vector competence for the two variants. This study aimed to: (1) map the spatiotemporal spread of CHIKV cases in Malaysia between 2009-2022; and (2) compare replication of E1-226A and E1-226V variants in the midguts and head/thoraxes of Ae. aegypti.

METHODOLOGY/PRINCIPAL FINDINGS: Spatiotemporal analysis of national notified CHIKV case addresses was performed. Between 2009-2022, 12,446 CHIKV cases were reported, with peaks in 2009 and 2020, and a significant shift from predominantly rural cases in 2009-2011 (85.1% rural), to urban areas in 2017-2022 (86.1% urban; p<0.0001). Two Ae. aegypti strains, field-collected MC1 and laboratory Kuala Lumpur (KL) strains, were fed infectious blood containing constructed CHIKV clones, pCMV-p2020A (E1-226A) and pCMV-p2020V (E1-226V) to measure CHIKV replication by real-time PCR and/or virus titration. The pCMV-p2020A clone replicated better in Ae. aegypti cell line Aag2 and showed higher replication, infection and dissemination efficiency in both Ae. aegypti strains, compared to pCMV-p2020V.

CONCLUSIONS/SIGNIFICANCE: This study revealed that a change in circulating CHIKV variants can be associated with changes in vector competence and outbreak epidemiology. Continued genomic surveillance of arboviruses is important.

PMID:39480893 | DOI:10.1371/journal.pntd.0012632

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Structural influences on synaptic plasticity: The role of presynaptic connectivity in the emergence of E/I co-tuning

PLoS Comput Biol. 2024 Oct 31;20(10):e1012510. doi: 10.1371/journal.pcbi.1012510. Online ahead of print.

ABSTRACT

Cortical neurons are versatile and efficient coding units that develop strong preferences for specific stimulus characteristics. The sharpness of tuning and coding efficiency is hypothesized to be controlled by delicately balanced excitation and inhibition. These observations suggest a need for detailed co-tuning of excitatory and inhibitory populations. Theoretical studies have demonstrated that a combination of plasticity rules can lead to the emergence of excitation/inhibition (E/I) co-tuning in neurons driven by independent, low-noise signals. However, cortical signals are typically noisy and originate from highly recurrent networks, generating correlations in the inputs. This raises questions about the ability of plasticity mechanisms to self-organize co-tuned connectivity in neurons receiving noisy, correlated inputs. Here, we study the emergence of input selectivity and weight co-tuning in a neuron receiving input from a recurrent network via plastic feedforward connections. We demonstrate that while strong noise levels destroy the emergence of co-tuning in the readout neuron, introducing specific structures in the non-plastic pre-synaptic connectivity can re-establish it by generating a favourable correlation structure in the population activity. We further show that structured recurrent connectivity can impact the statistics in fully plastic recurrent networks, driving the formation of co-tuning in neurons that do not receive direct input from other areas. Our findings indicate that the network dynamics created by simple, biologically plausible structural connectivity patterns can enhance the ability of synaptic plasticity to learn input-output relationships in higher brain areas.

PMID:39480889 | DOI:10.1371/journal.pcbi.1012510

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Comprehensive corrective exercise program improves ankle function in female athletes with limited weight-bearing ankle dorsiflexion: A randomized controlled trial

PLoS One. 2024 Oct 31;19(10):e0312152. doi: 10.1371/journal.pone.0312152. eCollection 2024.

ABSTRACT

Limited ankle dorsiflexion range of motion is one of the most important risk factors for lower limb injury, which changes the biomechanics and the neuromuscular control of the lower limb muscles. This study aims to test the effectiveness of a comprehensive corrective exercise program (CCEP) on the range of motion, proprioception, dynamic balance, and muscle activation in female athletes with limited weight-bearing lunge ankle dorsiflexion range of motion. 30 female athletes aged 15 to 25 years with dorsiflexion under 34° were randomized to two groups. The intervention group (n = 15) received eight weeks of CCEP including soft tissue mobilization, joint mobilization, stretching, and strengthening, and the control (n = 15) group did not receive any intervention. range of motion, proprioception, dynamic balance, and muscle activation were assessed before and after the intervention. The training group showed clinically acceptable and statistically significant changes in ankle dorsiflexion range of motion (ES = 0.714), balance (ES = 0.423), and proprioception (ES = 0.253; P < 0.05). There were significant changes in the activity of the tibialis anterior and soleus muscles in the dynamic overhead squat test (descending and ascending phases) and the activity of the medial gastrocnemius in the descending phase decreased significantly (P < 0.05). No significant change was observed in the activity of the peroneus longus muscle (P > 0.05). The findings show that CCEP appears to be beneficial in increasing dorsiflexion range of motion, proprioception, balance, and decreasing ankle muscle activity among individuals with limited ankle dorsiflexion. Improving the dorsiflexion range of motion may be promising for reducing ankle sprain injury.

PMID:39480882 | DOI:10.1371/journal.pone.0312152

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Nevin Manimala Statistics

Making the most of errors: Utilizing erroneous classifications generated by machine-learning models of neuroimaging data to capture disorder heterogeneity

J Psychopathol Clin Sci. 2024 Nov;133(8):678-689. doi: 10.1037/abn0000943.

ABSTRACT

Within-disorder heterogeneity complicates mapping the neurobiological features of psychopathology to Diagnostic and Statistical Manual of Mental Disorders conceptualizations. The present study explored the patterns of diagnostic classification errors among disorders with commonly co-occurring features to examine this heterogeneity. Classification analyses were conducted with the University of California, Los Angeles Phenomics Study database using a support-vector classifier to differentiate disorders via whole brain task-based functional connectivity, predicting that model misclassifications would provide insight about brain connectivity characteristics shared across disorders. Whether symptoms and specific brain networks could account for misclassification rates was also explored. The classification model performed better than chance (44% accuracy, p = .01) and revealed that misclassification of schizophrenia (SCZ) as bipolar disorder (BD; 38%) and BD as SCZ (36%) was symmetrical. Attention-deficit/hyperactivity disorder (ADHD) was misclassified as BD at the highest rate (46%) and higher than the converse (17%). SCZ and ADHD were misclassified least (15% SCZ as ADHD and 22% ADHD as SCZ). Considerable variance in misclassification of SCZ as BD (R2 = .83) and BD as SCZ (R2 = .71) could be accounted for by symptoms of both SCZ and BD. Permutation testing revealed disorder- and network-specific effects, with certain networks improving classification accuracy and others hindering it for specific disorders. An approach focused on classification errors replicated known disorder overlap, producing errors in the expected configuration. Further, it identified clinical and neural features within and across diagnostic categories that contribute to disorder misclassification and within-disorder heterogeneity. This approach may facilitate neurobiologically informed phenotypic differentiation within diagnostic groups. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

PMID:39480336 | DOI:10.1037/abn0000943

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The impact of posttraumatic stress disorder and head injury on reactive and appetitive aggression in adult Syrian refugees in Lebanon

Psychol Trauma. 2024 Oct 31. doi: 10.1037/tra0001796. Online ahead of print.

ABSTRACT

OBJECTIVE: Refugees are highly vulnerable to mental health disorders and head injuries. The primary aim of this study is to examine the impact of posttraumatic stress disorder (PTSD) and head injury on reactive and appetitive aggression in adult Syrian refugees in Lebanon.

METHOD: A cross-sectional study was conducted targeting adult Arab United Nations High Commissioner for Refugees-registered Syrian refugees residing in Beirut and southern regions of Lebanon. Eligible refugees completed a battery of questionnaires including the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, fifth edition, the Trauma Events and Head Injury sections of the Harvard Trauma Questionnaire, the Buss-Perry Aggression Questionnaire, and the Appetitive Aggression Scale.

RESULTS: A total of 191 Syrian refugees participated in the study: 62.83% were females, and the mean age was 31.01 years (SD = 10.98). The severity of PTSD (adjusted B = 0.18, 95% CI [0.05, 0.31], p = .006), having experienced at least one head injury trauma event (adjusted B = 10.20, 95% CI [1.61, 18.79], p = .020), and the severity of somatic symptoms (adjusted B = 0.71, 95% CI [0.23, 1.20], p = .004) were significant risk factors of reactive aggression. As for appetitive aggression, males (females adjusted OR [aOR] = 0.06, 95% CI [0.02, 0.18], p < .001), younger individuals (aOR = 0.95, 95% CI [0.91, 0.99], p = .024), and higher severity of somatic symptoms (aOR = 1.20, 95% CI [1.09, 1.32], p < .001) were significant risk factors.

CONCLUSIONS: PTSD and head injury are independent risk factors for reactive aggression but not appetitive aggression in Syrian refugees in Lebanon, while the severity of somatic symptoms is an independent risk factor for both reactive and appetitive aggression. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

PMID:39480320 | DOI:10.1037/tra0001796

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Can the subjective perception of trauma effectively differentiate between International Classification of Diseases-11 PTSD and complex PTSD? The 2022 Russian invasion analysis

Psychol Trauma. 2024 Oct 31. doi: 10.1037/tra0001801. Online ahead of print.

ABSTRACT

OBJECTIVE: This study is aimed to test the association of the Subjective Traumatic Outlook (STO) concept for distinguishing between posttraumatic stress disorder (PTSD) and complex PTSD. Focusing on identity dimensions within identity theory, the research aims to understand how subjective factors influence psychological outcomes, especially in the context of trauma during prolonged war. Findings can inform our understanding of the perception of trauma during wartime.

METHOD: We examined a national sample of 1,895 Ukrainians during the Russian invasion, who completed the International Trauma Questionnaire and the STO. Statistical analyses, including analysis of variance, analysis of covariance, and contrast measurement, were conducted to examine associations while controlling for demographic factors.

RESULTS: Our study highlights distinct STO levels associated with varying degrees of trauma-related disorders. Lower STO scores relate to reduced disorder likelihood, while higher STO levels indicate greater risk, particularly for complex PTSD. These distinctions persist even when considering demographic variables associated with wartime conditions.

CONCLUSION: Our research contributes to the understanding of PTSD/complex PTSD during ongoing conflict and underscores the applicability of identity aspects in elucidating the influence of subjective factors on psychological outcomes. This exploration of STO represents another approach to understanding internal perspectives in trauma-related disorders. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

PMID:39480319 | DOI:10.1037/tra0001801

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Change processes associated with functional improvement in a web-based version of Skills Training in Affective and Interpersonal Regulation (webSTAIR) for trauma-exposed veterans

J Consult Clin Psychol. 2024 Oct;92(10):698-710. doi: 10.1037/ccp0000906.

ABSTRACT

OBJECTIVE: In spite of the evidence that both symptom reduction and functional improvement are important for supporting recovery from trauma, psychotherapy process research has largely focused on mechanisms of symptom reduction. A better understanding of how change occurs in treatments that emphasize functional improvement rather than trauma processing is critical for optimizing effective, patient-centered care.

METHOD: This study involved secondary analysis of data collected in three multisite trials of a 10-module web-based version of Skills Training in Affective and Interpersonal Regulation, a skills-focused transdiagnostic intervention. The sample included 314 trauma-exposed veterans (38% male; 64% non-Hispanic White) who screened positive for elevated symptoms of posttraumatic stress disorder and/or depression. Latent change score modeling examined prospective relationships between changes from pre-to-mid and mid-to-post treatment in four potential mechanisms (emotion regulation, interpersonal problems, posttraumatic stress disorder symptoms, and depression symptoms) and the association of these changes with overall functional improvement (at posttreatment and follow-up).

RESULTS: Emotion regulation change during the first half of treatment predicted interpersonal and symptom improvements during the second half of treatment, but not vice versa. Changes in each potential mechanism were uniquely associated with functional improvement and together statistically accounted for 78% additional variance in functional improvement beyond what was associated with baseline functioning and covariates.

CONCLUSIONS: Results support emotion regulation as an early mechanism of transdiagnostic therapeutic change in web-based version of Skills Training in Affective and Interpersonal Regulation and highlight the relevance of all four potential mechanisms to functional improvement. The study contributes to an understanding of how change occurs in skills-focused interventions for trauma-exposed individuals. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

PMID:39480289 | DOI:10.1037/ccp0000906