Nevin Manimala

PLoS One. 2023 Jan 27;18(1):e0281070. doi: 10.1371/journal.pone.0281070. eCollection 2023.

ABSTRACT

Genome-wide association studies have greatly increased the number of T2DM associated risk variants but most of them have focused on populations of European origin. There is scarcity of such studies in developing countries including Pakistan. High prevalence of T2DM in Pakistani population prompted us to design this study. We have devised a two stage (the discovery stage and validation stage) case-control study in Pashtun ethnic population in which 500 T2DM cases and controls each have been recruited to investigate T2DM genetic risk variants. In discovery stage Whole Exome Sequencing (WES) was used to identify and suggest T2DM pathogenic SNPs, based on SIFT and Polyphen scores; whereas in validation stage the selected variants were confirmed for T2DM association using MassARRAY genotyping and appropriate statistical tests. Results of the study showed the target positive association of rs1801282/PPARG (OR = 1.24, 95%Cl = 1.20-1.46, P = 0.010), rs745975/HNF4A (OR = 1.30, 95%Cl = 1.06-1.38, P = 0.004), rs806052/GLIS3 (OR = 1.32, 95%Cl = 1.07-1.66, P = 0.016), rs8192552/MTNR1B (OR = 1.53, 95%Cl = 0.56-1.95, P = 0.012) and rs1805097/IRS-2 (OR = 1.27, 95%Cl = 1.36-1.92, P = 0.045), with T2DM; whereas rs6415788/GLIS3, rs61788900/NOTCH2, rs61788901/NOTCH2 and rs11810554/NOTCH2 (P>0.05) showed no significant association. Identification of genetic risk factors/variants can be used in defining high risk subjects assessment, and disease prevention.

PMID:36730981 | DOI:10.1371/journal.pone.0281070

J Acquir Immune Defic Syndr. 2022 Dec 12. doi: 10.1097/QAI.0000000000003147. Online ahead of print.

ABSTRACT

BACKGROUND: Early antiretroviral treatment (ART) improves outcomes in children, but few studies have comprehensively evaluated the impact of ART started from the first week of life.

METHODS: Children diagnosed with HIV within 96 hours of life were enrolled into the Early Infant Treatment Study in Botswana and followed on ART for 96 weeks. Nevirapine, zidovudine, and lamivudine were initiated; nevirapine was switched to lopinavir/ritonavir between weeks 2-5 in accordance with gestational age. Clinical and laboratory evaluations occurred at weeks 1, 2, 4, 8, 12, 24, 36, 48, 60, 72, 84, and 96.

FINDINGS: Forty children-initiated ART at a median of 2 (IQR 2, 3) days of life; 38 (95%) completed follow-up through 96 weeks, and 2 (5%) died between 12 and 24 weeks. ART was well tolerated; 9 (24%) children experienced a grade 3 or 4 hematologic event, and 2 (5%) required treatment modification for anemia. The median 96-week CD4 count was 1625 (IQR 1179, 2493) cells/mm3 with only 5/38 (13%) having absolute counts <1000 cells/mm3. Although 23 (61%) had at least one visit with HIV-1 RNA ≥40 copies/mL at or after 24 weeks, 28 (74%) had HIV-1 RNA <40 copies/mL at the 96-week visit. Median cell-associated HIV-1 DNA at 84/96-week PBMCs was 1.9 (IQR 1.0, 2.6) log10 copies/106 cells. Pre-ART reservoir size at birth was predictive of the viral reservoir at 84/96 weeks.

INTERPRETATION: Initiation of ART in the first week of life led to favorable clinical outcomes, preserved CD4 cell counts, and low viral reservoir through 96 weeks of life.

PMID:36729692 | DOI:10.1097/QAI.0000000000003147

J Acquir Immune Defic Syndr. 2022 Dec 12. doi: 10.1097/QAI.0000000000003149. Online ahead of print.

ABSTRACT

BACKGROUND: Adolescent girls and young women (AGYW) living with HIV who have higher stress levels may be at risk for stress-related biological alterations, which could influence HIV progression and adherence to antiretroviral therapy (ART).

SETTING: We aimed to estimate associations among stress-responsive biomarkers, ART adherence and viral suppression in AGYW living with HIV in South Africa. We also hypothesized that psychosocial stressors (e.g., depression, food insecurity, low socioeconomic status (SES), HSV-2) would be associated with higher biomarker levels.

METHODS: We utilized 2018/2019 data from the HIV Prevention Trials Network (HPTN) 068 cohort to assess associations between stress-responsive biomarkers and viral suppression (<1000 copies/mL) and ART adherence measured using dried blood spot (DBS) cards. Stress-responsive biomarkers included C-reactive protein (CRP), Herpes simplex virus type 1 (HSV-1), and cytomegalovirus (CMV) infection and reactivation. Associations were estimated using unadjusted log-binomial or ordinal logistic regression models.

RESULTS: In 166 AGYW living with HIV, there was no association between stress-responsive biomarkers and viral suppression or ART adherence. However, increased CRP levels were associated with higher HSV-2 infection (odds ratio (OR) 1.98; 95% confidence interval (CI) 1.11, 3.52), being a government grant recipient (OR 3.21; 95% CI 1.30, 7.92), lower food insecurity (OR 0.34; 95% CI 0.13, 0.90) and increased BMI (OR 1.07; 95% CI 1.01, 1.14).

CONCLUSIONS: High prevalence of psychosocial stressors and persistent herpesviruses in AGYW living with HIV has the potential to lead to poorer health outcomes. More research is needed to untangle relationships between economic stability, chronic disease, and chronic stress.

PMID:36729676 | DOI:10.1097/QAI.0000000000003149

J Acquir Immune Defic Syndr. 2022 Dec 12. doi: 10.1097/QAI.0000000000003145. Online ahead of print.

ABSTRACT

BACKGROUND: To collect and compare selected hearing measures in a pilot study of young adults with perinatally-acquired HIV (YAPHIV), and those with perinatal HIV-exposure, who are uninfected (YAPHEU).

SETTING: Cross-sectional hearing measures in YAPHIV and YAPHEU enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol (AMP) for Participants 18 Years of Age and Older (AMP Up).

METHODS: Pure-tone air conduction audiometry and distortion product otoacoustic emission (DPOAE) data were collected in one visit. A low-frequency pure-tone average (PTA) (LFPTA, at 0.25, 0.5, 1, and 2 kHz), a speech-frequency PTA (SFPTA, at 0.5, 1, 2, and 4 kHz), and a high-frequency PTA (HFPTA, at 3, 4, 6, and 8 kHz) were calculated. Hearing loss was defined as worse ear SFPTA ≥20 dB HL. Separate linear regression models were fit for worse ear LFPTA, SFPTA, and HFPTA to assess associations with PHIV status. DPOAE signal-to-noise ratios (SNRs) were obtained at three frequencies in each ear.

RESULTS: Forty-seven YAPHIV and 9 YAPHEU completed hearing testing. All adjusted mean PTAs were similar between YAPHIV and YAPHEU. Hearing loss occurred more in YAPHIV (7/47, 15.2%, 95% CI: 6.3%-28.9%), compared to YAPHEU (0/9, 0%). No associations were detected between HIV disease severity measures and worse ear SFPTA. DPOAE SNRs were similar between YAPHIV and YAPHEU.

CONCLUSIONS: In this pilot study, peripheral hearing (i.e., PTAs) and cochlear function (i.e., DPOAEs) were similar between YAPHIV and YAPHEU. A larger study is warranted to confirm these findings.

PMID:36729663 | DOI:10.1097/QAI.0000000000003145

Cornea. 2022 Dec 13. doi: 10.1097/ICO.0000000000003201. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study was to compare the performance of Kerasave and Optisol-GS for hypothermic corneal storage for 14 days.

METHODS: This study was a prospective laboratory investigation. Mate corneas were recovered into Kerasave or Optisol-GS (27 pairs) and stored at 2°C to 8°C for 14 days. Corneas were evaluated by trained eye bank technicians, and study parameters were compared between the initial and final evaluations. Endothelial cell density (ECD), hexagonality (HEX), and coefficient of variation (CV) were evaluated by specular microscopy, and central corneal thickness (CCT) was examined by optical coherence tomography after 1, 3, 7, and 14 days of storage. Corneal transparency was scored using slit lamp examination at days 1 and 14.

RESULTS: Average ECD, HEX, and CV for the Kerasave (2653 ± 303 cells/mm2, 57 ± 4%, and 36 ± 3%) and Optisol-GS (2623 ± 306 cells/mm2, 57 ± 5%, and 36 ± 4%) groups were not significantly different at day 1. There was also no difference at any other study time points (all P > 0.05). ECD did not significantly change from day 1 to day 14 in either group (P > 0.05), but a statistically significant change in HEX and CV was observed between day 1 and day 14 in both groups (P < 0.01). Average CCT measured at day 1 for corneas stored in Kerasave was 622 ± 49 μm and those stored in Optisol-GS was 580 ± 35 μm (P < 0.01). The difference in CCT measurements was not significantly different at day 14 (Kerasave: 674 ± 46 μm vs. Optisol-GS: 647 ± 58 μm, P > 0.05). Corneal transparency was not significantly different between the 2 groups at day 1 or day 14.

CONCLUSIONS: The corneal quality and clinically relevant parameters including ECD, endothelial morphometry, and corneal transparency were not different in corneas stored in Kerasave or Optisol-GS for 14 days. The initial difference in CCT between the 2 groups decreased at day 14. These results demonstrated that Kerasave corneal storage solution preserves the corneal endothelium similarly to Optisol-GS.

PMID:36729660 | DOI:10.1097/ICO.0000000000003201

Am J Audiol. 2023 Feb 2:1-12. doi: 10.1044/2022_AJA-22-00119. Online ahead of print.

ABSTRACT

PURPOSE: Optimal measurement settings to measure the medial olivocochlear reflex (MOCR) in humans have not yet been defined. The purpose of this study was to advance the representation of the MOCR in auditory brainstem response (ABR) as an addition to the current diagnostic portfolio.

PARTICIPANTS AND METHOD: Twelve female and 14 male normal-hearing adults participated in the study. Potential effects of a contralateral acoustic stimulus (CAS) on amplitude changes were investigated by recording ABR waveform profiles on the left side at click intensities of 50/60/70 dB nHL with and without CAS (60 dB SPL). Secondly, to detect potential chronological order influences, measurement settings were rearranged on the right side and measurements were repeated. Additionally, ABR thresholds were recorded with and without a CAS in 10 patients.

RESULTS: When the effect of contralateral suppression was analyzed on the basis of amplitude changes, there was a change under administration of the CAS signal that was statistically significant. Interestingly, the order of recordings affected the degree of amplitude change. In three out of 10 patients, reproducible suppression effects on ABR thresholds were detectable upon CAS presentation.

CONCLUSIONS: To our knowledge, this is the largest study dealing with the recording of the MOCR elicited by a contralateral noise via ABR in normal-hearing individuals. Effects of MOCR are measurable via amplitude changes upon CAS administration. Chronological orders influence the impact of this effect on amplitude changes. Optimal measurement settings have not yet been defined. However, experiments such as this study may help to further improve measurements, and thus advance the representation of the MOC reflex in ABR as an addition to the current diagnostic portfolio.

PMID:36729649 | DOI:10.1044/2022_AJA-22-00119

Cornea. 2022 Dec 13. doi: 10.1097/ICO.0000000000003185. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this study was to comprehensively evaluate the patient-reported quality-of-life (QoL) outcomes after corneal cross-linking for keratoconus.

METHODS: This Save Sight Keratoconus Registry study used cross-sectional and longitudinal designs. For the cross-sectional study, 532 patients with keratoconus (mean age 30.9 ± 11.9 years; 31.6% female) completed the Keratoconus Outcomes Research Questionnaire (KORQ) and 343 patients with keratoconus (mean age 28.3 ± 10.7 years; 32.7% female) completed the Impact of Vision Impairment (IVI) questionnaires. Similarly, for the longitudinal study, 39 patients (mean age 24.2 ± 8.4 years; 23.1% female) completed the KORQ and 16 patients (mean age 27.9 ± 17.1 years; 50.0% female) completed the IVI questionnaire before and after 6 months of cross-linking. The QoL data were analyzed using the Andrich Rating Scale Model of Rasch analysis.

RESULTS: For both cross-sectional and longitudinal studies, the KORQ and IVI scales demonstrated satisfactory psychometric properties [ordered and well-spaced categories, variance explained by the measure 52%-73%, person separation index 2.4-3.9, and fit statistics <1.3 (most cases)]. The patients who had not undergone corneal cross-linking had worse mean activity limitation than those with cross-linking (P = 0.008). However, the differences in symptoms and emotional scores between the groups were not statistically significant (both P > 0.05). The longitudinal study showed that cross-linking was associated with improved activity limitation, symptoms, and emotional scores.

CONCLUSIONS: The KORQ and IVI are psychometrically robust tools to evaluate the QoL outcomes of corneal cross-linking. Cross-linking is associated with improved activity limitation, symptoms, and emotional status.

PMID:36729643 | DOI:10.1097/ICO.0000000000003185

Med Sci Sports Exerc. 2022 Dec 14. doi: 10.1249/MSS.0000000000003103. Online ahead of print.

ABSTRACT

PURPOSE: The purpose was to examine the physiological responses resulting from an acute blood flow restriction (BFR) resistance exercise bout with two different cuff pressures in young, healthy men and women.

METHODS: Thirty adults (18-30 yr) completed a bilateral leg extension BFR bout consisting of four sets (30-15-15-15 repetitions) with cuffs applied at pressures corresponding to 40% and 60% of the minimum arterial occlusion pressure (AOP) needed to completely collapse the femoral arteries. During each of these conditions (40% and 60% AOP), physiological measures of near-infrared spectroscopy (NIRS) and electromyographic amplitude (EMG AMP) were collected from the dominant or non-dominant vastus lateralis. After each set, ratings of perceived exertion (RPE) were collected, whereas only at baseline and at the end of the bout, mean arterial pressure (MAP) was assessed. Separate mixed-factorial ANOVAs were used to examine mean differences in the change in EMG AMP and NIRS-parameters during each set. The absolute RPE and MAP values were also examined with separate ANOVAs. A p-value ≤0.05 was considered statistically significant.

RESULTS: Regardless of sex or cuff pressure, the change in EMG amplitude was lower in set 1 (14.8%) compared to the remaining sets (22.6 – 27.0%). The 40% AOP condition elicited the greatest changes in oxy[heme] and deoxy[heme], while also providing lower RPEs. For MAP there was an effect for Time such that MAP increased from pre (87.5 ± 4.3 mmHg) to post-exercise (104.5 ± 4.1 mmHg).

CONCLUSIONS: The major findings suggested that the 40% AOP condition permitted the greatest amount of recovery during the inter-set rest. Additionally, there did not appear to be any meaningful sex-related difference in this sample of young healthy adults.

PMID:36729632 | DOI:10.1249/MSS.0000000000003103

Sex Transm Dis. 2022 Dec 14. doi: 10.1097/OLQ.0000000000001743. Online ahead of print.

ABSTRACT

BACKGROUND: The 2021 CDC STI treatment guidelines recommend extragenital testing for gonorrhea and chlamydia in men who have sex with men (MSM) and for women based on reported behaviors and exposures. The “IWantTheKit (IWTK)” program is a free online platform for specimen self-collection and mail-in for combined chlamydia/gonorrhea testing. We sought to assess the additional diagnostic value of extragenital testing compared to genital testing only for chlamydia/gonorrhea and determine factors associated with a positive extragenital test among IWTK users.

METHODS: From August 2013 to January 2022, 7,612 unique IWTK users returned swabs for testing; 3,407 (45%) users requested both genital and extragenital tests and were included in this analysis. Descriptive statistics summarized demographic characteristics, reported behaviors, and genital and extragenital test results, data were stratified by gender and age group. A logistic regression model was used to estimate associations between factors and extragenital STI positivity.

RESULTS: Chlamydia positivity was 4.7%, 2.4% and 1.5% at genital, extragenital and both sites were positive, respectively; for gonorrhea, 0.4%, 1.1% and 0.4% were positive at those sites, respectively. Among women, age 25 and younger was significantly associated with extragenital chlamydia, OR = 4.0 (p = 0.010). Being in high risk quiz score group was associated with extragenital chlamydia (OR = 2.6, p = 0.005), and extragenital gonorrhea in men and women (OR = 8.5, p = 0.005).

CONCLUSION: Extragenital testing detected additional chlamydia and gonorrhea cases in the IWTK user population that would have been missed by genital only testing, especially for females <25 years and people reported high risk.

PMID:36729630 | DOI:10.1097/OLQ.0000000000001743

J Am Assoc Nurse Pract. 2022 Dec 14. doi: 10.1097/JXX.0000000000000809. Online ahead of print.

ABSTRACT

Many interdisciplinary oral health education programs have been implemented for pediatric primary care providers (e.g., pediatric nurse practitioner [PNP]) to raise awareness and gain skills related to the prevention of early childhood caries (ECC). However, no studies have evaluated if these educational programs provided to PNPs during their training resulted in clinical practice behavior changes. A 33-item survey was designed on a web-based platform (Survey Monkey) and distributed to 71 PNP graduates. The survey included demographics, current clinical practice, clinical practice behaviors, and perceived barriers to practice. Descriptive statistics were used to assess the survey items and thematic analyses on the open-ended questions. The survey response rate was 70% (50/71 PNPs). Most practicing PNPs were in acute care or specialty clinics (n = 33; 66%) where oral health was not part of the focused visit. Majority used knowledge learned in assessment and anticipatory guidance skills. However, only 14% of primary care providers were applying fluoride varnish with 10% billing for this procedure. Barriers to application were time, available supplies, COVID protocols, lack of support staff, or not billing due to minimal reimbursement. Many primary care-trained PNPs were practicing in acute or subspecialty areas where prevention of ECC is not viewed as part of their focused visit. Pediatric nurse practitioners working in primary care demonstrated some clinical practice changes. However, areas for improvement are time to perform a risk assessment and application of fluoride varnish, access to these supplies, and standard billing and insurance reimbursement for these preventable services.

PMID:36729598 | DOI:10.1097/JXX.0000000000000809