Nevin Manimala

Indian J Pediatr. 2022 Sep 6. doi: 10.1007/s12098-022-04311-z. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess cardiorespiratory fitness in children and adolescents with overweight/obesity using the Kasch pulse recovery (KPR) test, and its correlation with severity of obesity, insulin resistance, and blood pressure (BP).

METHODS: This is a retrospective analysis of baseline data from a study evaluating the efficacy of yoga for reduction of body mass index (BMI) in children aged 8-15 y with overweight/obesity. KPR three-minute step test was done. Children were classified into cardiorespiratory fitness categories based on the post-KPR heart rate (HR); the maximal oxygen consumption (VO₂ max) was calculated, and the correlation analysis was done.

RESULTS: One hundred fifty-five children with mean age of 11.6 ± 1.8 y and mean BMI of 26.2 ± 4.1 kg/m² were included. Mean post-KPR-HR and calculated VO₂ max were 119 ± 14 per minute and 48.7 ± 5.6 mL/kg/min, respectively. In children < 13 y, cardiorespiratory fitness was excellent or very good in 28%, good or sufficient in 58%, and poor or very poor in 14%. BMI, waist circumference (WC), resting HR, systolic BP, and homeostatic model of insulin resistance (HOMA-IR) were higher among those with poor/very poor fitness, with WC z score being statistically significant (p = 0.015). Post-KPR-HR showed positive correlation with BMI z score (r = 0.16, p = 0.044), WC z score (r = 0.21, p = 0.011), and HOMA-IR (r = 0.22, p = 0.012).

CONCLUSION: In children with overweight/obesity, 14% had poor cardiorespiratory fitness. Post-KPR-HR and calculated VO₂ max had good correlation with measures of obesity and HOMA-IR. Further studies evaluating cardiorespiratory fitness and normative data of VO₂ max for Indian children are warranted.

PMID:36066791 | DOI:10.1007/s12098-022-04311-z

J Neurooncol. 2022 Sep 6. doi: 10.1007/s11060-022-04124-2. Online ahead of print.

ABSTRACT

PURPOSE: To report the results of systematic meningioma screening program implemented by French authorities in patients exposed to progestin therapies (cyproterone (CPA), nomegestrol (NA), and chlormadinone (CMA) acetate).

METHODS: We conducted a prospective monocentric study on patients who, between September 2018 and April 2021, underwent standardized MRI (injection of gadolinium, then a T2 axial FLAIR and a 3D-T1 gradient-echo sequence) for meningioma screening.

RESULTS: Of the 210 included patients, 15 (7.1%) had at least one meningioma; seven (7/15, 47%) had multiple meningiomas. Meningiomas were more frequent in older patients and after exposure to CPA (13/103, 13%) compared to NA (1/22, 4%) or CMA (1/85, 1%; P = 0.005). After CPA exposure, meningiomas were associated with longer treatment duration (median = 20 vs 7 years, P = 0.001) and higher cumulative dose (median = 91 g vs. 62 g, P = 0.014). Similarly, their multiplicity was associated with higher dose of CPA (median = 244 g vs 61 g, P = 0.027). Most meningiomas were ≤ 1 cm³ (44/58, 76%) and were convexity meningiomas (36/58, 62%). At diagnosis, patients were non-symptomatic, and all were managed conservatively. Among 14 patients with meningioma who stopped progestin exposure, meningioma burden decreased in 11 (79%) cases with no case of progression during MR follow-up.

CONCLUSION: Systematic MR screening in progestin-exposed patients uncovers small and multiple meningiomas, which can be managed conservatively, decreasing in size after progestin discontinuation. The high rate of meningiomas after CPA exposure reinforces the need for systematic screening. For NA and CMA, further studies are needed to identify patients most likely to benefit from screening.

PMID:36066786 | DOI:10.1007/s11060-022-04124-2

Ann Biomed Eng. 2022 Sep 6. doi: 10.1007/s10439-022-03050-8. Online ahead of print.

ABSTRACT

Osteoporosis-related hip fragility fractures are a catastrophic event for patient lives but are not frequently observed in prospective studies, and therefore phase III clinical trials using fractures as primary clinical endpoint require thousands of patients enrolled for several years to reach statistical significance. A novel answer to the large number of subjects needed to reach the desired evidence level is offered by In Silico Trials, that is, the simulation of a clinical trial on a large cohort of virtual patients, monitoring the biomarkers of interest. In this work we investigated if statistical aliasing from a custom anatomy atlas could be used to expand the patient cohort while retaining the original biomechanical characteristics. We used a pair-matched cohort of 94 post-menopausal women (at the time of the CT scan, 47 fractured and 47 not fractured) to create a statistical anatomy atlas through principal component analysis, and up-sampled the atlas in order to obtain over 1000 synthetic patient models. We applied the biomechanical computed tomography pipeline to the resulting virtual cohort and compared its fracture risk distribution with that of the original physical cohort. While the distribution of femoral strength values in the non-fractured sub-group was nearly identical to that of the original physical cohort, that of the fractured sub-group was lower than in the physical cohort. Nonetheless, by using the classification threshold used for the original population, the synthetic population was still divided into two parts of approximatively equal number.

PMID:36066781 | DOI:10.1007/s10439-022-03050-8

Mol Biol Rep. 2022 Sep 6. doi: 10.1007/s11033-022-07884-2. Online ahead of print.

ABSTRACT

BACKGROUND: An inability of a man to conceive a potentially fertile woman after a year of unprotected intercourse is defined as male infertility. It is reported that 30-40% of males in their reproductive years have abnormalities in sperm production, either qualitatively or quantitatively, or both. However, genetic factors result in up to 15% of male infertility cases. The present study aimed to analyze the possible correlations between sub-fertility and polymorphisms in sperm mitochondrial CO3, ATP6 and ATP8 genes in sub-fertile men.

METHODS AND RESULTS: For 67 sub-fertile and 44 fertile male samples, Sanger sequencing of selected mitochondrial DNA genes was done. A total of twelve SNPs in the MT-CO3 gene: rs2248727, rs7520428, rs3134801, rs9743, rs28358272, rs2853824, rs2856985, rs2854139, rs41347846, rs28380140, rs3902407, and 28,411,821, fourteen SNPs in the MT-ATP6: rs2001031, rs2000975, rs2298011, rs7520428, rs9645429, rs112660509, rs6650105, rs6594033, rs6594034, rs6594035, rs3020563, rs28358887, rs2096044, and rs9283154, and ten SNPs in the MT-ATP8: rs9285835, rs9285836, rs9283154, rs8179289, rs121434446, rs1116906, rs2153588, rs1116905, rs1116907, and rs3020563 were detected in the case and control groups at different nucleotide positions. Only the rs7520428 in the MT-CO3 and MT-ATP6 showed a statistically significant difference between sub-fertile and fertile groups in the genotype’s and allele’s frequency test (P < 0.0001 for both).

CONCLUSION: The results of our study suggest that male sub-fertility is linked with rs7520428 SNP in MT-CO3 and MT-ATP6. The studied polymorphic variations in the MT-ATP8 gene, on the contrary, did not reveal any significant association with male sub-fertility.

PMID:36066780 | DOI:10.1007/s11033-022-07884-2

Environ Monit Assess. 2022 Sep 6;194(10):732. doi: 10.1007/s10661-022-10438-5.

ABSTRACT

Member states of the United Nations Convention to Combat Desertification are required to report on the proportion of land that is degraded in their countries, a requirement that is also tied into the UN Sustainable Development Goals (SDGs). National land degradation assessments are often conducted with the use of remote sensing data which are not always ground truthed. Google Street View (GSV) provides high resolution, panoramic imagery across large parts of the world that has the potential to be used to ground truth land degradation assessments. We apply three different methodologies (visual interpretation of GSV images, GSV image classification and vegetation index extraction) to derive vegetation cover estimates from Google Street View imagery for the Hardeveld bioregion of the Succulent Karoo biome in South Africa. Visual estimates of cover best predict known habitat condition values (adjusted R² = 0.86), whilst estimates derived from an unsupervised classification of GSV images also predict habitat condition relatively well (adjusted R² = 0.52). These results show the potential for using GSV imagery, and other large collections of ground-level landscape photographs, as a rough ground-truthing tool, especially in instances where more traditional ground-truthing approaches are not possible.

PMID:36066776 | DOI:10.1007/s10661-022-10438-5

Pediatr Nephrol. 2022 Sep 6. doi: 10.1007/s00467-022-05722-y. Online ahead of print.

ABSTRACT

BACKGROUND: The Kidney Donor Risk Index (KDRI) by Rao et al. was developed to measure the quality of kidney allografts. While Rao’s KDRI has been found to be a robust measure of kidney allograft survival for adult kidney transplant recipients, many studies have indicated the need to create a distinct pediatric KDRI.

METHODS: Our retrospective study utilized data from the United Network for Organ Sharing database. We examined 9295 deceased donor recipients’ data for age < 18 years from 1990 to 2020. We performed a multivariate Cox regression to determine the significant recipient and transplant factors impacting pediatric kidney allograft survival.

RESULTS: Multivariate analysis found 5 donor factors to be independently associated with graft failure or recipient death: age, female sex, anoxia as the cause of death, history of cigarette use, and cold ischemia time. Using receiver operator characteristic (ROC) curve analysis and analyzing the predictive value of each KDRI at 1, 5, and 10 years, the proposed pediatric KDRI had a statistically significant and higher predictive value for pediatric recipients at 5 (0.60 versus 0.57) and 10 years (0.61 versus 0.57) than the Rao KDRI.

CONCLUSIONS: The proposed pediatric KDRI may provide a more accurate and simpler index to assess the quality of kidney allografts for pediatric recipients. However, due to the mild increase in predictive capabilities over the Rao index, the study serves as a proof of concept to develop a pediatric KDRI. Further studies should focus on increasing the index’s predictive capabilities. A higher resolution version of the Graphical abstract is available as Supplementary information.

PMID:36066770 | DOI:10.1007/s00467-022-05722-y

AIDS Behav. 2022 Sep 6. doi: 10.1007/s10461-022-03821-3. Online ahead of print.

ABSTRACT

A pilot cluster randomized controlled trial involving two HIV clinics in the Dominican Republic assessed preliminary efficacy of an urban garden and peer nutritional counseling intervention. A total of 115 participants (52 intervention, 63 control) with moderate or severe food insecurity and sub-optimal antiretroviral therapy (ART) adherence and/or detectable viral load were assessed at baseline, 6- and 12-months. Longitudinal multivariate regression analysis controlling for socio-demographics and accounting for serial cluster correlation found that the intervention: reduced the prevalence of detectable viral load by 20 percentage points at 12 months; reduced any missed clinic appointments by 34 and 16 percentage points at 6 and 12 months; increased the probability of “perfect” ART adherence by 24 and 20 percentage points at 6 and 12 months; and decreased food insecurity at 6 and 12 months. Results are promising and warrant a larger controlled trial to establish intervention efficacy for improving HIV clinical outcomes.Trial registry Clinical Trials Identifier: NCT03568682.

PMID:36066760 | DOI:10.1007/s10461-022-03821-3

Sci Rep. 2022 Sep 5;12(1):15096. doi: 10.1038/s41598-022-17108-z.

ABSTRACT

Scalp melanoma (SM) has a worse prognosis than melanoma in other locations likely because of late diagnosis due to hair coverage, difficulties in interpreting dermoscopy findings, and its unique molecular profile. We aimed to describe the clinical, histopathological, molecular, and dermoscopic patterns of SM and its relation to androgenetic alopecia/elastosis at the tumor site. Through a retrospective cross-sectional study, we identified all SM diagnosed at the A.C.Camargo Cancer Center between 2008 and 2018. In all, 48 SM were analyzed: 45.8% of which exhibited moderate/severe androgenetic alopecia and 54.1% exhibited elastosis. Androgenetic alopecia/elastosis at the site of the SM was associated with older age (p < 0.001), chronic sun damage (p < 0.001), lentigo maligna subtype (p = 0.029), and photodamaged dermoscopic pattern (p < 0.001). Additionally, 41 cases were evaluated with a 14-gene panel: 53.7% displayed mutations and 46.3% were wild-type. BRAF mutations were most common (77%), with BRAF V600K being more frequent (50%) than BRAF V600E (31.2%). The NF1 gene was evaluated in 40 samples, of which 20% exhibited mutations. SM presents differently in areas covered by hair compared to in areas with androgenetic alopecia. Patients without alopecia may have higher Breslow thickness due to late diagnosis because of hair concealment. The high frequency of detrimental mutations can also explain the poor prognosis of SM.

PMID:36064728 | DOI:10.1038/s41598-022-17108-z

Orphanet J Rare Dis. 2022 Sep 5;17(1):342. doi: 10.1186/s13023-022-02472-w.

ABSTRACT

BACKGROUND: Niemann-Pick disease type C1 (NPC1) is a rare autosomal recessive disease characterized by endolysosomal accumulation of unesterified cholesterol with progressive deterioration in swallowing, often leading to premature death. Although documented, the natural history of NPC1 swallowing dysfunction has yet to be delineated systematically. This manuscript aims to provide a comprehensive characterization of the phenotypic spectrum and progression of swallowing dysfunction in NPC1.

METHODOLOGY: The National Institutes of Health (NIH) NPC1 natural history study (NCT00344331) enrolled 120 patients, who underwent comprehensive interpretative swallow assessments for swallowing safety, dietary modifications, and aspiration risk. Longitudinal statistical modeling accounted for all outcomes with NPC1 disease covariates (first symptom onset, age at neurological symptom onset, seizure history, duration of neurological symptoms) as well as miglustat use (a glucosylceramide synthase inhibitor) and NIH study duration (NIHSD; the length of time an individual participated in the NIH study). Probabilities for disease progression and time to swallowing decline were conducted for the entire cohort.

RESULTS: Time to swallowing decline with American Speech-Language-Hearing Association National Outcome Measure (ASHA-NOMS) and the NIH-adapted Penetration Aspiration Scale (NIH-PAS) were identified: [Formula: see text] person-years and [Formula: see text] person-years, respectively. NIHSD and seizure history consistently and significantly were associated with decline (OR_NIHSD = 1.34-2.10, 95% CI 1.04-3.4, p = 0.001-0.026; OR_Seizure = 3.26-18.22, 1.03-167.79; p = 0.001-0.046), while miglustat use revealed protection (OR_Miglustat = 0.01-0.43, 0.007-0.98; p = 0.001-0.044). The probability of decline with NPC1 neurological severity scale and annual severity increment scale were established with the aforementioned covariates, varying amongst subgroups.

CONCLUSION: This study represents the most extensive collection of prospective, instrumental swallowing assessments in NPC1 to date with an interpretive analysis providing an improved understanding of NPC1 disease progression with swallowing function-serving as a foundation for clinical management and future NPC1 therapeutics.

PMID:36064725 | DOI:10.1186/s13023-022-02472-w

J Neuroinflammation. 2022 Sep 5;19(1):217. doi: 10.1186/s12974-022-02573-0.

ABSTRACT

BACKGROUND: Neuroinflammation is emerging as an important pathological process in frontotemporal dementia (FTD), but biomarkers are lacking. We aimed to determine the value of complement proteins, which are key components of innate immunity, as biomarkers in cerebrospinal fluid (CSF) and plasma of presymptomatic and symptomatic genetic FTD mutation carriers.

METHODS: We measured the complement proteins C1q and C3b in CSF by ELISAs in 224 presymptomatic and symptomatic GRN, C9orf72 or MAPT mutation carriers and non-carriers participating in the Genetic Frontotemporal Dementia Initiative (GENFI), a multicentre cohort study. Next, we used multiplex immunoassays to measure a panel of 14 complement proteins in plasma of 431 GENFI participants. We correlated complement protein levels with corresponding clinical and neuroimaging data, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP).

RESULTS: CSF C1q and C3b, as well as plasma C2 and C3, were elevated in symptomatic mutation carriers compared to presymptomatic carriers and non-carriers. In genetic subgroup analyses, these differences remained statistically significant for C9orf72 mutation carriers. In presymptomatic carriers, several complement proteins correlated negatively with grey matter volume of FTD-related regions and positively with NfL and GFAP. In symptomatic carriers, correlations were additionally observed with disease duration and with Mini Mental State Examination and Clinical Dementia Rating scale® plus NACC Frontotemporal lobar degeneration sum of boxes scores.

CONCLUSIONS: Elevated levels of CSF C1q and C3b, as well as plasma C2 and C3, demonstrate the presence of complement activation in the symptomatic stage of genetic FTD. Intriguingly, correlations with several disease measures in presymptomatic carriers suggest that complement protein levels might increase before symptom onset. Although the overlap between groups precludes their use as diagnostic markers, further research is needed to determine their potential to monitor dysregulation of the complement system in FTD.

PMID:36064709 | DOI:10.1186/s12974-022-02573-0