Nevin Manimala

PLoS One. 2021 Aug 3;16(8):e0255368. doi: 10.1371/journal.pone.0255368. eCollection 2021.

ABSTRACT

Most of our knowledge on reproductive biology of gray whales dates back to scientific research conducted during commercial whaling in the late 1950s and 1960s. The goal of the present study was to provide updated insights on reproductive physiology of gray whales, using progesterone and testosterone as biomarkers. We measured hormone concentrations using enzyme immunoassay (EIA) techniques in blubber biopsies collected from 106 individual whales from March to November over a span of 12 years (2004-2016) between California and Alaska. We found testosterone concentrations in males to increase significantly with age (P = 0.03). Adult males showed significantly elevated testosterone concentrations when sampled in the fall compared to the summer (P = 0.01), likely indicating physiological preparation for mating. We measured testosterone concentrations in females of different age classes, but no statistical differences were found. We found significantly higher progesterone concentrations in pregnant females compared to non-pregnant females and adult males (P< 0.001), indicating progesterone is a valid biomarker for pregnancy in gray whales. Both female and male calves had elevated progesterone concentrations, suggesting maternal transfer via lactation. We fit a mixture of two normal distributions to progesterone data from all non-calf females to identify clusters of high and low progesterone and estimated the probability of being pregnant for whales of unknown reproductive status. With this approach we identified likely pregnant and non-pregnant animals. This study represents an important milestone on reproductive profiles in this population, that can be used to estimate more accurate and precise reproductive parameters to be used for better understanding population dynamics of gray whales.

PMID:34343192 | DOI:10.1371/journal.pone.0255368

PLoS One. 2021 Aug 3;16(8):e0254955. doi: 10.1371/journal.pone.0254955. eCollection 2021.

ABSTRACT

PURPOSE: To investigate the impact of large choroidal vessels (LCV) on Choriocapillaris (CC) flow deficit (FD) analyses with swept-source optical coherence tomography angiography (SS-OCTA).

DESIGN: Prospective, cross-sectional study.

METHODS: Macular 6x6mm SS-OCTA scans were obtained from intermediate age-related macular degeneration (iAMD) and healthy eyes. Images were captured and processed according to most common standards and analyzed for percentage of flow-deficits (FD%) within four 1x1mm squares at the corners of each image. Choroidal thickness (CT), iris color and refraction error were considered as potential influential factors for LCV visibility. A linear mixed model and logistic regression models were calculated for statistical evaluation.

RESULTS: Sixty-nine iAMD and 49 age-matched healthy eyes were enrolled. LCV were visible in at least one sector in 52% of iAMD and 47% of healthy eyes. Within the iAMD group FD% were significantly lower in areas containing LCV (p = 0.0029). Increasing CT resulted in an odds ratio decrease of LCV (OR: 0.94, p<0.0001). Below a CT value of ≤118μm LCV could be expected with a sensitivity of 86% and a specificity of 85%.

CONCLUSIONS: LCV can significantly affect CC FD analyses of SS-OCTA images. Their visibility is negatively associated with CT. The impact of LCV should be taken into account when performing CC FD assessments, especially in patients where reduced CT is to be expected and inclusion of affected areas should be considered carefully.

PMID:34343177 | DOI:10.1371/journal.pone.0254955

J Hypertens. 2021 Aug 2. doi: 10.1097/HJH.0000000000002944. Online ahead of print.

ABSTRACT

BACKGROUND: Orthostatic hypotension is an independent risk factor for cardiovascular morbidity and mortality. Arterial stiffness has been shown to be a pathophysiological mechanism linking orthostatic hypotension and increased cardiovascular risk. This study aims to evaluate the relationship between arterial stiffness, orthostatic hypotension and subendocardial viability ratio (SEVR) and moreover to identify the main predictors of orthostatic hypotension, carotid-femoral pulse wave velocity (PWV-cf) and SEVR.

METHODS: Seventy-five patients were enrolled (mean age 82.95 ± 6.45) in Verona’s AOUI Geriatric ward. They underwent blood pressure, heart rate, body weight measurements and also comorbidity, arterial stiffness (PWV-cf measured by applanation tonometry), SEVR and biochemical indexes.

RESULTS: Prevalence of orthostatic hypotension was 46.6%. Even after adjustment for age, sex, glomerular filtration rate and mean arterial pressure, SEVR values corrected for arterial oxygen and haemoglobin content were statistically lower in orthostatic hypotension patients (P = 0.05) and PWV-cf values were statistically higher in orthostatic hypotension individuals (P = 0.042). In a binary logistic regression, PWV-cf was the only significant predictor of orthostatic hypotension (odds ratio 1.123; P = 0.039; confidence interval = 1.006–1.17).In a backward logistic regression model sex, creatinine clearance and orthostatic hypotension were significant predictors of SEVR corrected for O2 content. Mean arterial pressure, creatinine clearance and orthostatic hypotension were significant predictors of PWV-cf.

CONCLUSION: This study shows that orthostatic hypotension is related to increased arterial stiffness, confirming its higher prevalence in elderly patients. Orthostatic hypotension was also associated with reduced values of corrected SEVR, showing a relevant consequence of orthostatic hypotension on subendocardial perfusion impairment.

PMID:34343144 | DOI:10.1097/HJH.0000000000002944

Curr Opin Neurol. 2021 Aug 2. doi: 10.1097/WCO.0000000000000986. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS) is an archetypal complex disease wherein disease risk and severity are, for the majority of patients, the product of interaction between multiple genetic and environmental factors. We are in a period of unprecedented discovery with new large-scale genome-wide association study (GWAS) and accelerating discovery of risk genes. However, much of the observed heritability of ALS is undiscovered and we are not yet approaching elucidation of the total genetic architecture, which will be necessary for comprehensive disease subclassification.

RECENT FINDINGS: We summarize recent developments and discuss the future. New machine learning models will help to address nonlinear genetic interactions. Statistical power for genetic discovery may be boosted by reducing the search-space using cell-specific epigenetic profiles and expanding our scope to include genetically correlated phenotypes. Structural variation, somatic heterogeneity and consideration of environmental modifiers represent significant challenges which will require integration of multiple technologies and a multidisciplinary approach, including clinicians, geneticists and pathologists.

SUMMARY: The move away from fully penetrant Mendelian risk genes necessitates new experimental designs and new standards for validation. The challenges are significant, but the potential reward for successful disease subclassification is large-scale and effective personalized medicine.

PMID:34343141 | DOI:10.1097/WCO.0000000000000986

Clin Exp Dermatol. 2021 Aug 3. doi: 10.1111/ced.14870. Online ahead of print.

ABSTRACT

BACKGROUND: Although MDA-5 autoantibodies are widely explored in dermatomyositis (DM), most studies relied on MDA-5 autoantibody testing performed in research settings and not with the now-available commercial laboratory tests.

OBJECTIVE: To characterize the clinical and histopathologic data in patients with DM and circulating MDA5-autoantibodies, as defined by commercial-based testing.

METHODS: Retrospective review of patients with DM who underwent MDA-5 antibody testing. All available skin biopsy slides were reviewed.

RESULTS: Cutaneous features more prevalent in MDA-5 positive DM included Raynaud syndrome (p <0.0001), cutaneous ulcerations (p=0.013), mechanic hands (p=0.0164), palmar papules (p=0.004), oral ulcers (p=0.024) and alopecia (p= 0.027). Joint and pulmonary involvement were more frequently in patients with MDA-5 positive DM (both p<0.0001) as was dysphagia (p=0.0029). Myopathy (p=0.404) and malignancy (p=0.342) were not statistically different between the cohorts. Vasculopathy was more frequent in MDA-5 positive DM (p=0.005), while spongiosis was less (p=0.016).

CONCLUSIONS: This study not only confirmed some known associations between disease manifestations and MDA-5 autoantibody status, as determined by commercially-available testing, but also identified new associations, including Raynaud syndrome and dysphagia.

PMID:34342883 | DOI:10.1111/ced.14870

J Am Geriatr Soc. 2021 Aug 3. doi: 10.1111/jgs.17382. Online ahead of print.

ABSTRACT

BACKGROUND: To demonstrate feasibility and utility of the iPad version of the NIH Toolbox Cognition Battery (NIHTB-CB) in a clinical trial of older adults.

METHODS: Fifty-one adults, aged 55 and older without dementia were tested twice on NIHTB-CB and more traditional paper-and-pencil neuropsychological measures after meal ingestion, with approximately a 4-week interval. We also compared performances at Time 1 and Time 2 for significant change. We also extracted the response times and errors for available NIHTB-CB subtests to determine subtle changes in performance.

RESULTS: Over the interval, improvement in fluid cognitive measures was noted at Time 2 (t = -3.07, p = 0.004), whereas crystallized measures were unchanged. Tests of fluid cognition negatively correlated with age, particularly for the second visit. Analysis of the average speed per item showed that, for two of the tests, speed increased at Time 2. Traditional neuropsychological tests correlated with many of the NIHTB-CB measures. Response times for all five timed tests decreased at Time 2, although only statistically significant for Picture Sequence and Picture Vocabulary.

CONCLUSIONS: The iPad version of the NIH Toolbox Cognition Battery appears to be an adequate measure to assess cognitive functioning in a clinical trial of older adults. Psychometric analyses suggest stability in measures of crystallized functioning, whereas measures of fluid abilities revealed improvements over the short time frame of the study. Response times and errors for individual tests revealed intriguing relationships that should be further evaluated to determine the utility in clinical sample analysis, as this could aid identification of subtle cognitive change over short periods. Additional studies with larger sample sizes will be helpful to understanding the reliability, sensitivity, and specificity of the NIHTB-CB sub-scores in older adults. In addition, further evaluations with clinical populations, including individuals with cognitive impairment, are warranted.

PMID:34342879 | DOI:10.1111/jgs.17382

Eur Cell Mater. 2021 Aug 3;41:63-71. doi: 10.22203/eCM.v042a05.

ABSTRACT

This study presents a simple and cost-effective model using microparticles to simulate the bacterial distribution pattern in soft tissue after low- and high-pressure irrigation. Silica coated iron microparticles [comparable diameter (1 µm) and weight (0.8333 pg) to Staphylococcus aureus] were applied to the surface of twenty fresh human muscle tissue samples in two amputated lower legs. Particle dissemination into deep tissue layers as an undesired side effect was investigated in four measuring fields as positive control (PC) as well as after performing pulsatile high-pressure (HP, 8 measuring fields) and low-pressure flushing (LP, 8 measuring fields). Five biopsies were taken out of each measuring field to get a total number of 100 biopsies. After histological and digital image processing, the specimens were analysed, and all incomplete sections were excluded. A special detection algorithm was parameterised using the open source bioimage analysis software QuPath. The application of this detection algorithm enabled automated counting and detection of the particles with a sensitivity of 95 % compared to manual counts. Statistical analysis revealed significant differences (p < 0.05) in our three different sample groups: HP (M = 1608, S = 302), LP (M = 2176, SD = 609) and PC (M = 4011, SD = 686). While both HP and LP flushing techniques are able to reduce the number of bacteria, a higher effectiveness is shown for HP irrigation. Nevertheless, a challenge for the validity of the study is the use of dead tissue and therefore a possible negative influence of high-pressure irrigation on tissue healing and further dispersion of particles cannot be evaluated.

PMID:34342876 | DOI:10.22203/eCM.v042a05

Musculoskelet Surg. 2021 Aug 3. doi: 10.1007/s12306-021-00726-7. Online ahead of print.

ABSTRACT

PURPOSE: To assess the complications and second surgeries rates at 1 year follow-up in a group of patients underwent minimally invasive fixation with screws or hybrid external fixation (HEF) for tibial plateau fractures (TPF). The hypothesis was that low Schatzker (I-IV) TPF would have shown a lower complication rate with respect to high Schatzker (V-VI) TPF.

METHODS: 148 patients who underwent minimally invasive surgery with screws or HEF for TPF were included and pooled in two groups: mono-condylar (Schatzker I-IV) and bi-condylar (Schatzker V-VI). The rate of second surgeries and complications, such as stiffness, infection, wound dehiscence and malunion occurred within 1 year, were reported.

RESULTS: Statistically significant difference between mono-condylar and bi-condylar groups was found in terms of stiffness (18% vs. 37%, p = 0.01), malunion (4% vs 21%, p = 0.004) and second surgeries (32% vs. 48%, p = 0.049). Associated procedures performed during TPF fixation increased risk of second surgeries (OR 2.1, p < 0.001). No differences in terms of second surgeries and complications were found in bi-condylar group treated with screws and HEF.

CONCLUSION: Bi-condylar TPF treated with minimally invasive surgery developed a significantly higher rates of stiffness, malunion and second surgeries within 1 year compared to mono-condylar fractures. Moreover, when an associated procedure was performed, the risk of a reoperation was nearly doubled. Trial registration number PG 0012506 CE AVEC 620/2018/Oss/IOR.

PMID:34342873 | DOI:10.1007/s12306-021-00726-7

J Racial Ethn Health Disparities. 2021 Aug 3. doi: 10.1007/s40615-021-01124-2. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic Hepatitis B virus infection, the leading cause of hepatocellular carcinoma worldwide, disproportionately affects Asian Pacific Islanders (APIs) within the USA. Among APIs, the Hmong have one of the highest rates of chronic HBV infection-up to 18% compared to 0.1% for non-Hispanic Caucasians. This study sought to estimate the prevalence of HBV infection and assess the need for community HBV education within Milwaukee County’s Hmong.

METHODS: Between 3/2013 and 12/2019, 287 Hmong participants were screened for HBV and 271 were provided targeted HBV education to evaluate its impact on HBV knowledge.

RESULTS: Among participants screened, 178 (62%) were immune; 77 (27%) susceptible; 27 (9%) positive; and 5 (2%) in a “gray zone.” Targeted health education showed statistically significant improvement in HBV knowledge.

DISCUSSION: With 38% lacking immunity to HBV and 9% with active infection, there remains a significant need for HBV screening, vaccination, and education in Milwaukee’s Hmong community.

PMID:34342867 | DOI:10.1007/s40615-021-01124-2

J Neurovirol. 2021 Aug 3. doi: 10.1007/s13365-021-01003-w. Online ahead of print.

ABSTRACT

This study aims to characterize the acute neurological manifestations caused by DENV, ZIKV, and YFV during hospitalization; identify the risk factors associated with persistent neurological complications after discharge; and evaluate the time to resolution during clinical follow-up. A prospective study evaluated 505 children, between March 2014 and July 2019, hospitalized with neurological manifestations and that doctors suspected infection of the central nervous system (CNS). Viral infection of collected cerebrospinal fluid (CSF) was confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR). Patients were clinically followed up after hospital discharge. Analysis of predictive factors and survival curves was performed. This study identified clinical symptoms and changes in the CSF laboratory, electroencephalogram (EEG), and CNS image as predictors of complications in children with confirmed infection in the CNS by DENV, ZIKV, or YFV. No statistical difference was found (p value 0.574) in the time to the resolution of complications in children after hospital discharge between the three types of flaviviruses. Children with YFV, detected in CSF samples, had a 53% higher risk of developing neurological complications. Performing etiological diagnosis by RT-PCR of CSF samples of children with neurological manifestations, especially during Flavivirus outbreaks, is an essential tool for improving the prognosis and clinical follow-up of these patients.

PMID:34342850 | DOI:10.1007/s13365-021-01003-w