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Nevin Manimala Statistics

Factors Associated With Fertility Preservation in a Pediatric, Adolescent and Young Adult Population

J Pediatr Hematol Oncol. 2022 Aug 9. doi: 10.1097/MPH.0000000000002515. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the patient characteristics associated with pursuing fertility preservation (FP) before gonadotoxic therapy in a pediatric, adolescent and young adult patient population.

METHODS: This is a retrospective cohort study of patient data at Cincinnati Children’s Hospital Medical Center. Demographics, clinical diagnoses, and treatment characteristics were compared between participants that selected FP versus those that declined. Variables were analyzed separately for males and females by logistic regression.

RESULTS: Patients with a hematologic cancer were less likely to be eligible for preservation: 53.9% of ineligible males, P<0.001, and 51.8% of ineligible females, P<0.0001. Among patients who were candidates for FP, those receiving high-risk therapy were more likely to elect for FP (65.3% males, P<0.0001, and 87.5% of females, P<0.0001). Pubertal males were more likely to undergo preservation than prepubertal males (70.5% vs. 29.5%, P<0.0001; however, this trend was not demonstrated among female patients. In both males and females, race, ethnicity, religion, primary language, and insurance status were not shown to be statistically significant factors in predicting utilization of FP.

CONCLUSION: Risk of infertility, type of cancer, and developmental status influenced decisions on pursuing FP in pediatric, adolescent and young adult patients facing iatrogenic infertility.

PMID:35972939 | DOI:10.1097/MPH.0000000000002515

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A prospective follow-up study on how long newborns are fasting in Debre Markos Comprehensive Specialized Hospital, Ethiopia, 2020

PLoS One. 2022 Aug 16;17(8):e0268558. doi: 10.1371/journal.pone.0268558. eCollection 2022.

ABSTRACT

BACKGROUND: At birth, continuous flow of nutrients to the fetus in utero interrupted due to cut of the route /umbilical cord/. Instead of the cord, breast-mouth connection will be the next route in the extra uterine life. Nevertheless, limited data in our locality show the duration for how long immediate newborns are fasting.

OBJECTIVE: This study aimed to assess time to initiation of breastfeeding and its predictors among postnatal mothers within 12 hours of birth in Debre Markos Comprehensive Specialized Hospital, North West Ethiopia, 2020.

METHODS: A Facility based prospective follow-up study was conducted among 475 participants who were selected using systematic random sampling techniques. To collect the data, techniques including interview, chart review and observation were used. Data was entered to Epi-data version 3.1 and analyzed by STATA 14 software. A cox proportional hazards regression model was fitted to identify predictors for survival time. Results of the final model were expressed in terms of adjusted hazard ratio (AHR) with 95% confidence interval, statistical significance was declared with P-value is less than 0.05.

RESULTS: Newborns were fasting breast-milk for the median time of 2 hours. In this study, 25% of participants initiated breastfeeding within 1 hour, pre-lacteal while 75% initiated within 3 hours. Gave birth to multiple babies (AHR 0.37, 95% CI (0.19, 0.69)), operative delivery (AHR 0.77, 95% CI (0.62, 0.96)), got advice on timely initiation of breastfeeding immediately after delivery (AHR 0.79, 95% CI (0.63, 0.97)), pre-lacteal feeding initiation (AHR 10.41, 95% CI (2.82, 38.47)) and neonatal sickness (AHR 0.08, 95% CI (0.03-0.19)) were statistically significant predictors for time to initiation of breastfeeding.

CONCLUSION: Fifty percent of mothers initiated breastfeeding within 2 hours. Most of them didn’t initiate breastfeeding based on world health organization’s recommendation, within one hour after delivery. Multiple birth, operative delivery, getting advice on timely initiation of breastfeeding immediately after delivery, giving pre-lacteal feeding and neonatal sickness were found to be predictors of time to initiation of breastfeeding.

PMID:35972926 | DOI:10.1371/journal.pone.0268558

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Knockdown of GSG2 inhibits the development and progression of non-small cell lung cancer in vitro and in vivo

Cell Cycle. 2022 Aug 16:1-12. doi: 10.1080/15384101.2022.2110441. Online ahead of print.

ABSTRACT

Lung cancer has been recognized as the most common malignant neoplasm of the respiratory system with extremely high morbidity, among which non-small cell lung cancer (NSCLC) accounts for the majority. Many published literatures have revealed the roles of GSG2 in the progression of ovarian cancer, bladder cancer and breast cancer. However, there were no reports on the relationship between GSG2 and NSCLC. Herein, GSG2 was identified as a potential tumor promoter in NSCLC development, whose abundant expression was observed in NSCLC tissues compared with adjacent nonmalignant tissues and statistically correlated with more advanced tumor stage, more malignant grade and higher risk of lymphatic metastasis. Subsequent in vitro loss-of-function experiments indicated that GSG2 depletion could arrest cell cycle and suppress cell proliferation and migration while enhancing cell apoptosis. At the same time, the suppressive effects of GSG2 depletion on NSCLC development were verified by in vivo experiments. In conclusion, the current study identified GSG2 as a tumor promoter in development and progression of NSCLC, which could work as a novel therapeutic target for NSCLC.

PMID:35972887 | DOI:10.1080/15384101.2022.2110441

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Segmental Slope is a Predictor of Fusion Rate in Single Level Anterior Cervical Discectomy and Fusion

Global Spine J. 2022 Aug 16:21925682221120533. doi: 10.1177/21925682221120533. Online ahead of print.

ABSTRACT

STUDY DESIGN: Retrospective study.

OBJECTIVES: To explore preoperative segmental slope as a predictor of fusion rate after single-level anterior cervical discectomy and fusion (ACDF).

METHODS: Data of consecutive patients with single-level cervical spondylosis who underwent ACDF between 2011 and January 2019 were retrospectively reviewed. Preoperative parameters including baseline characteristics, segment slope, T1 slope, range of motion, intervertebral disk height, and bone density were evaluated. Data were analyzed using Student’s t-test, Mann-Whitney U test, χ2 test, Fisher’s exact test, multivariate logistic regression analysis, and receiver operating characteristic curve.

RESULTS: In total, 253 patients were selected. The mean follow-up was 32.1 months (range 24-99 months). Male sex, body mass index, preoperative segment slope, T1 slope, operative levels, and osteoporosis or osteopenia were associated with non-fusion at an early stage after surgery. However, no statistically significant difference was observed at the last follow-up. Multivariate logistic regression analysis revealed that the preoperative segment slope was an independent predictor for non-fusion at 3, 6, and 12 months postoperatively. Osteoporosis or osteopenia was an independent predictor of non-fusion at 6 and 12 months postoperatively. The area under the curve was .874 at 3 months (P < .001, cutoff value 10.21°), .888 at 6 months (P < .001, cutoff value 14.56°), and .825 at 12 months (P < .001, cutoff value 21.08°).

CONCLUSION: Preoperative segment slope can be used as a predictor of early fusion rate after single-level ACDF. We determined detailed cutoff values. This study may help surgeons take measures to promote early fusion in advance.

PMID:35972886 | DOI:10.1177/21925682221120533

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Effectiveness of an Interactive, Highly Tailored “Video Doctor” Intervention to Suppress Viral Load and Retain Patients With HIV in Clinical Care: A Randomized Clinical Trial

J Acquir Immune Defic Syndr. 2022 Sep 1;91(1):58-67. doi: 10.1097/QAI.0000000000003045. Epub 2022 Jun 27.

ABSTRACT

BACKGROUND: To determine whether Positive Health Check, a highly tailored video doctor intervention, can improve viral suppression and retention in care.

SETTING: Four clinics that deliver HIV primary care.

METHODS: A hybrid type 1 effectiveness-implementation randomized trial design was used to test study hypotheses. Participants (N = 799) who were not virally suppressed, were new to care, or had fallen out of care were randomly assigned to receive Positive Health Check or the standard of care alone. The primary endpoint was viral load suppression, and the secondary endpoint was retention in care, both assessed at 12 months, using an intention-to-treat approach. A priori subgroup analyses based on sex assigned at birth and race were examined as well.

RESULTS: There were no statistically significant differences between Positive Health Check (N = 397) and standard of care (N = 402) for either endpoint. However, statistically significant group differences were identified from a priori subgroup analyses. Male participants receiving Positive Health Check were more likely to achieve suppression at 12 months than male participants receiving standard of care adjusted risk ratio [aRR] [95% confidence interval (CI)] = 1.14 (1.00 to 1.29), P = 0.046}. For retention in care, there was a statistically significant lower risk for a 6-month visit gap in the Positive Health Check arm for the youngest participants, 18-29 years old [aRR (95% CI) = 0.55 (0.33 to 0.92), P = 0.024] and the oldest participants, 60-81 years old [aRR (95% CI) = 0.49 (0.30 to 0.81), P = 0.006].

CONCLUSIONS: Positive Health Check may help male participants with HIV achieve viral suppression, and younger and older patients consistently attend HIV care.

REGISTRY NAME: Positive Health Check Evaluation Trial. Trial ID: 1U18PS004967-01. URL: https://clinicaltrials.gov/ct2/show/NCT03292913.

PMID:35972854 | DOI:10.1097/QAI.0000000000003045

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Disruption in accessing sexual and reproductive health services among border populations during COVID-19 lockdown in Uganda

J Glob Health. 2022 Aug 17;12:04065. doi: 10.7189/jogh.12.04065.

ABSTRACT

BACKGROUND: The spread of COVID-19 exposed the inadequacies inherent in the health care systems of many countries. COVID-19 and the attendant demands for emergency treatment and management put a significant strain on countries’ health care systems, including hitherto strong health systems. In Uganda, as the government strived to contain COVID-19, other essential health care services were either disrupted or completely crowded out. Balancing the provision of COVID-19 treatment and management services and at the same time offering sexual and reproductive health and rights services (SRHR) proved to be a considerable challenge in these circumstances. COVID-19 prevention-related travel restrictions and border closures had far-reaching negative consequences on the mobility of individuals to access essential health services in Uganda. The situation may have been worse for cross-border communities that sometimes access services across the borders.

METHODS: Using quantitative data from 1521 respondents and qualitative data (20 key informant interviews and 12 focus group discussions), we investigate the disruption in accessing SRHR services for border communities in Uganda during COVID-19.

RESULTS: Results indicate that females (adjusted odds ratio (aOR) = 1.3; 95% confidence interval CI = 1.08-1.79), those with primary education (aOR = 1.47; 95% CI = 1.61-2.57), currently employed (aOR = 2.03; 95% CI = 1.61-2.57) and those with the intention to leave current residence (aOR = 2.09; 95% CI = 1.23-3.55) were more likely to have experienced a disruption in accessing SRHR services. However, respondents aged 35 years, or more were less likely to have experienced a disruption compared to their younger counterparts.

CONCLUSIONS: Results shed light on the disruption of access toSRHR services during pandemics such as COVID-19 among a highly mobile population. There is a need to invest in building strong and resilient health care systems that can guarantee continuous access to essential health services including SRHR provisions among mobile populations during pandemics.

PMID:35972848 | DOI:10.7189/jogh.12.04065

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Strategies to identify causal common genetic variants and corresponding effector genes for paediatric obesity

Pediatr Obes. 2022 Aug 16:e12968. doi: 10.1111/ijpo.12968. Online ahead of print.

ABSTRACT

BACKGROUND: Childhood obesity rates are on the rise, but there are currently no effective therapies available to slow or halt their progression. Although environmental and lifestyle factors have been implicated in its pathogenesis, childhood obesity is considered a complex disorder with a clear genetic component. Intense genome-wide association study (GWAS) efforts through large-scale collaborations have enabled the discovery of genetic loci robustly associated with childhood obesity beyond the classic FTO locus. That said, GWAS itself does not pinpoint the actual underlying causal effector genes, but rather just yields association signals in the genome.

OBJECTIVE: This review aims to outline what has been elucidated thus far on the genetic aetiology of commong childhood obesity and to describe strategies to identify and validate both causal common genetic variants and their corresponding effector genes.

RESULTS: Relevant cell types for molecular studies can be identified by gene set enrichment analysis and considering known biology of obesity-related physiological processes. Putatively causal single nucleotide polymorphisms (SNPs) can be identified by several methods including statistical fine mapping and ‘assay for transposase accessible chromatin sequencing’ (ATAC-seq). Variant to gene mapping can then nominate effector genes likely regulated by cis-regulatory elements harbouring putatively causal SNPs. A SNP’s cis-regulatory activity can be functionally validated by several in vitro methods including luciferase assay and CRISPR approaches. These CRISPR approaches can also be used to investigate how dysregulatn of effector genes may confer obesity risk.

CONCLUSION: Uncovering the causative genes related to GWAS signals and elucidating their functional contributions to paediatric obesity with these strategies will deepen our understanding of this disease and serve better treatment outcomes.

PMID:35971868 | DOI:10.1111/ijpo.12968

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Durable scalable 3D SLA-printed cuff electrodes with high performance carbon + PEDOT:PSS-based contacts

Artif Organs. 2022 Aug 16. doi: 10.1111/aor.14387. Online ahead of print.

ABSTRACT

BACKGROUND: The stimulation and recording performance of implanted neural interfaces are functions of the physical and electrical characteristics of the neural interface, its electrode material and structure. Therefore, rapid optimization of such characteristics is becoming critical in most clinical and research studies. This paper describes the development of an upgraded 3D printed cuff electrode shell design containing a novel intrinsically conductive polymer (ICP) for stimulation and recording of peripheral nerve fibers.

METHODS: A 3D stereolithography (SLA) printer was used to print a scalable, custom designed, C-cuff electrode and I-beam closure for accurate, rapid implementation. A novel contact consisting of a percolated carbon graphite base electrodeposited with an intrinsically conductive polymer (ICP), poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) produced a PEDOT:PSS + carbon black (CB) matrix that was used to form the electrochemical interface on the structure. Prototype device performance was tested both in-vitro and in-vivo for electrical chemical capacity, electrochemical interfacial impedance, surgical handling, and implantability. The in-vivo work was performed on the sciatic nerve of 25 anesthetized Sprague Dawley rats to demonstrate recording and stimulating ability.

RESULTS: Prototypes of different spatial geometries and number of contacts (bipolar, tripolar, and tetrapolar) were designed. The design was successfully printed with inner diameters down to 500μm. Standard bipolar and tripolar cuffs, with a 1.3 mm inner diameter (ID), 0.5 mm contact width, 1.0 mm pitch, and a 1.5 mm end distance were used for the functional tests. This geometry was appropriate for placement on the rat sciatic nerve and enabled in-vivo testing in anesthetized rats. The contacts on the standard bipolar electrode had an area of 2.1×10-2 cm2 . Cyclic voltammetry on ICP coated and uncoated graphite contacts showed that the ICP increased the average charge storage capacity (CSC) by a factor of 30. The corresponding impedance at 1 Hz was slightly above 1 kΩ, a 99.99% decrease from 100 kΩ in the uncoated state. The statistical comparison of the pre- versus post-stimulation impedance measurements were not significantly different (p-value >0.05) CONCLUSIONS: The new cuff electrode enables rapid development of cost-effective functional stimulation devices targeting nerve bundles less than 1.0 mm in diameter. This allows for recording and modulation of a low-frequency current targeted within the peripheral nervous system.

PMID:35971860 | DOI:10.1111/aor.14387

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Autoimmune hepatitis and metabolic syndrome-associated disease development: a U.S. cohort study

Aliment Pharmacol Ther. 2022 Aug 16. doi: 10.1111/apt.17191. Online ahead of print.

ABSTRACT

BACKGROUND: Autoimmune hepatitis (AIH) may coexist with metabolic syndrome-associated diseases (MSADs) given patients’ inherent need for corticosteroid therapy, as well as general population trends.

AIM: To examine the impact of MSAD risk factors on AIH or its treatment, and vice versa METHODS: This was a multi-centre retrospective cohort study of 552 patients with AIH diagnosed between January 2000 and December 2019. Data relating to demographic factors, laboratory values, AIH medications and MSADs were collected at diagnosis and at 1- and 3-year follow-up. Statistical relationships were analysed and reported.

RESULTS: We included 552 patients in the study cohort (median age 50 years, 76.1% female). All MSADs, including hypertension, dyslipidaemia, diabetes and a gain of BMI ≥3 kg/m2 , increased within the AIH cohort over time. Initial treatment regimen impacted de novo diabetes but not other MSAD development. AIH biochemical remission was less frequent at 3 years post-diagnosis among patients with ≥1 MSAD. The incidence of new MSADs could be predicted by baseline factors in certain cases.

CONCLUSION: In the largest US-based cohort of patients newly diagnosed with AIH, there was a considerable burden of pre-existing and de novo MSADs that may affect AIH treatment outcomes. Identifying those at highest risk of co-morbid MSADs allows for an individualised approach to management to reduce its long-term sequelae in patients with AIH.

PMID:35971856 | DOI:10.1111/apt.17191

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Serum exosome inflamma-miRs are surrogate biomarkers for asthma phenotype and severity

Allergy. 2022 Aug 16. doi: 10.1111/all.15480. Online ahead of print.

ABSTRACT

BACKGROUND: Asthma is a heterogeneous disease with several phenotypes, endotypes and severity degrees, in which different T cell subpopulations are involved. These cells express specific miRNAs (i.e., inflamma-miRs) that can be released to serum in exosomes after activation and be used as biomarkers of underlying inflammation. Thus, we aim to evaluate specific T cell miRNA signatures in serum exosomes from different subgroups of asthmatic patients.

METHODS: Samples from healthy donors (N=30) and patients (N=119) with different asthma endotypes (T2high -Atopic/T2high -Non atopic/T2low ) and severity degrees (mild/MA and moderate-severe/MSA) were used. Demographic, clinical, haematological and biochemical characteristics were collected. Twelve miRNAs previously associated with different Th subsets were preselected and their levels in serum exosome samples were measured using RTqPCR.

RESULTS: We detected five miRNAs with high confidence in serum exosomes: miR-16-5p, miR-21-5p, miR-126-3p, miR146a-5p, and miR-215-5p. All of them, except miR-16-5p were upregulated in MSA patients compared to MA. A logistic regression model including each of these miRNAs was created to discriminate both conditions, rendering a ROC curve AUC of 0.896 (0.830-0.961). miR-21-5p and miR-126-3p, both involved in Th1/Th2 differentiation, were specifically augmented in T2high -Atopic patients. Of note, all these changes were found in samples collected in autumn. On the other hand, IL-6high patients with MSA, which were more obese, older, with higher neutrophil and basophil counts and TNF levels, displayed a decrease of miR-21-5p, miR-126-3p, and miR-146a-5p.

CONCLUSION: Immune-related miRNAs, including miR-21-5p, miR-126-3p, miR-146a-5p, and miR-215-5p can be used as clinically relevant non-invasive biomarkers of the phenotype/endotype and severity of asthma.

PMID:35971848 | DOI:10.1111/all.15480