Category: Nevin Manimala

Sleep Breath. 2022 Jul 30. doi: 10.1007/s11325-022-02665-4. Online ahead of print.

ABSTRACT

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) and asthma are two diseases with a high epidemiological impact that may often coexist. Both diseases have underlying pathogenic mechanisms (chronic inflammation, genetic predisposition, etc.); it is still unclear whether or not their coexistence is due to a specific pathophysiological factor. In the literature, the pathogenesis of OSAS has four pathophysiological traits: one or more anatomical predisposing factors, a low arousal threshold (low AT), high loop gain, and poor muscle responsiveness. In this study, we hypothesized that a low AT is a common pathophysiological factor in OSAS and asthma.

METHODS: A retrospective study of patients attending the Pulmonology Unit of the University Hospital of Trieste was carried out. Low AT was predicted on the bases of the following polysomnography features, as previously shown by Edwards et al.: an AHI of < 30 events/h, a nadir SpO2 of > 82.5%, and a hypopnea fraction of total respiratory events of > 58.3%.

RESULTS: Thirty-five patients with asthma and OSAS and 36 with OSAS alone were included in the study. Low AT was present in 71% of patients affected by asthma and OSAS (25 patients out of 35) versus 31% (11 patients out of 36) of patients affected by OSAS alone with a statistically significant difference (p = 0.002) between the two groups. Stratifying for BMI and OSAS severity, the difference between groups remained statistically significant.

CONCLUSIONS: This is the first study to describe specific polysomnographic characteristics of patients affected by asthma and OSAS. A low AT may well be the pathophysiological factor common to the two diseases. If confirmed by other studies, this finding could lead to the presence of asthma and OSAS in the same individual being considered a syndrome with a common pathophysiological factor.

PMID:35907116 | DOI:10.1007/s11325-022-02665-4

Neurol Sci. 2022 Jul 30. doi: 10.1007/s10072-022-06298-z. Online ahead of print.

ABSTRACT

BACKGROUND: Levodopa is the most commonly used first-line drug for Parkinson’s disease. However, during the period of medication, the generation of motor fluctuations affects the life quality of patients. CVT-301, as an inhaled levodopa for the treatment of OFF episodes, rose in response to this condition.

METHODS: We systematically searched Medline, EMBASE, Cochrane Library, and Clinicaltrials.gov for relevant randomized controlled trials, from the earliest available date to February 12, 2022, to evaluate the efficacy of high and low dose of inhaled levodopa in patients with Parkinson’s disease.

RESULTS: A total of six multicenter, randomized controlled trials with 1166 patients were included. Compared with placebo, CVT-301 has a statistically significant effect on the treatment of Parkinson’s patients with OFF episodes of medication interval. The UPDRS Part III score decreased more significantly in the high-dose group 30 minutes after administration than the low-dose group (WMD = – 4.51; 95% CI, – 7.34 to – 1.68; p = 0.002). More patients in the high-dose group achieved and maintained an on state up to 60 min after receiving study medication (RR = 1.17; 95% CI, 1.08 to 1.27; p < 0.001). And more patients were proved with improved PGIC scores in the high-dose group (RR = 1.13; 95% CI, 1.05 to 1.21; p = 0.001).

CONCLUSIONS: High doses CVT-301 can improve the motor function of the patient to some extent. There seems no risk of increasing adverse reactions.

PMID:35907110 | DOI:10.1007/s10072-022-06298-z

J Behav Med. 2022 Jul 30. doi: 10.1007/s10865-022-00343-0. Online ahead of print.

ABSTRACT

The well-being of caregivers and their care recipients is interrelated, although conflicting evidence has emerged across different caregiving populations. Using data from the National Health and Aging Trends Study and the National Study of Caregiving (2015 and 2017, n = 742 dyads), we constructed actor-partner interdependence models assessing how spillover (i.e., interdependence) of depressed mood varied by care recipient health condition (specifically cancer, dementia, stroke, and diabetes) and kinship type (spouse/partner, child, other relative, or non-relative). Across condition types, care recipient-to-caregiver partner effects were significantly larger in dyads with vs. without cancer and significantly smaller in dyads with vs. without diabetes (p_interactions < .05). Substantive differences in partner effects were observed by kinship type, although moderation was not statistically significant. The findings highlight potential heterogeneity in caregiver-care recipient interdependence with implications for future research and delivery of supportive care.

PMID:35907099 | DOI:10.1007/s10865-022-00343-0

Endocrine. 2022 Jul 30. doi: 10.1007/s12020-022-03140-6. Online ahead of print.

ABSTRACT

PURPOSE: This study aims to evaluate the correlations between the severity of the disease and serum steroid levels by analyzing the serum steroid levels in COVID-19 patients with different levels of disease progression and the control group.

METHODS: Morning serum Aldosterone, 11-deoxycortisol, Androstenedione, 17-hydroxyprogesterone, Dihydrotestosterone (DHT), Dehydroepiandrosterone (DHEA), Corticosterone, Dehydroepiandrosterone sulfate (DHEAS), Estrone, Estradiol, Progesterone, 11-deoxycorticosterone, Cortisol, Corticosterone, Androsterone, Pregnenolone, 17-hydroxypregnenolone and 21-deoxycortisol levels were measured in 153 consecutive patients were grouped as mild, moderate, and severe based on the WHO COVID-19 disease severity classification and the control group. Steroid hormone levels were analyzed at once with a liquid chromatography-tandem mass spectrometric method (LC-MS/MS).

RESULTS: In our study, nearly all steroids were statistically significantly higher in the patients’ group than in the control group (p < 0.001). Also, DHEA was an independent indicator of the disease severity with COVID-19 CONCLUSIONS: Our study reveals that the alteration in steroid hormone levels was correlated with disease severity. Also, steroid hormone levels should be followed up during COVID-19 disease management.

PMID:35907083 | DOI:10.1007/s12020-022-03140-6

Bratisl Lek Listy. 2022;123(7):475-48. doi: 10.4149/BLL_2022_075.

ABSTRACT

BACKGROUND: Risk for developing papillary thyroid carcinoma (PTC), the most common endocrine malignancy, is thought to be mediated by lifestyle, environmental exposures and genetic factors. Recent progress in the genome-wide association studies of thyroid cancer leads to the identification of several genetic variants conferring risk to this malignancy across different ethnicities.

METHODS AND RESULTS: We set out to elucidate the impact of selected single nucleotide polymorphisms (SNPs) on papillary thyroid carcinoma risk and to evaluate the interactions of these genetic variants with associated diseases for the first time in the Slovak population. Six SNPs (rs966423, rs2439302, rs965513, rs116909374, rs1537424 and rs944289) were genotyped in 86 patients with PTC and 99 healthy control subjects. The association analysis and multivariable modelling of PTC risk by the genetic factors, supplemented with a rigorous statistical validation, were performed. One of the six SNPs rs966423 (DIRC3, OR=1.51, p=0.03) was significantly associated with PTC. Next two SNPs rs965513 (PTCSC2, OR=1.34) and rs116909374 (MBIP, OR=0.44) showed a suggestive association. Haplotype TTC (SNPs located on chromosome 14q13) showed a suggestive association with PTC (p=0.07, OR=1.55). In the PTC group, significant associations were observed between rs966423 (DIRC3) and ischemic heart diseases (p=0.009), rs965513 (PTCSC2) and diabetes mellitus (p=0.04) and haplotype 14q13 and musculoskeletal diseases. Next three associations rs966423 (DIRC3) and arterial hypertension; rs116909374 (MBIP) and other benign diseases; rs1537424 (MBIP) and disorder lipid metabolism, rs965513 (PTCSC2) and anti-Tg (thyroglobulin antibody) showed suggestive associations.

CONCLUSION: These results indicate that germline variants not only predispose to PTC, but may also be related to other risk factors, including associated diseases. However, these associations were only moderate, and further multi-ethnic studies are required to evaluate the usefulness of these germline variants in the clinical stratification of PTC patients (Tab. 8, Ref. 37).

PMID:35907052 | DOI:10.4149/BLL_2022_075

J Assist Reprod Genet. 2022 Jul 30. doi: 10.1007/s10815-022-02582-1. Online ahead of print.

ABSTRACT

PURPOSE: The latest treatments do not sufficiently prevent miscarriage and fetal growth restriction (FGR) in pregnant women. Here, we assessed the effects of a human protein, CTRP6, that specifically inhibits the activation of the alternative complement pathway on miscarriage, fetal and placental development.

METHODS: Pregnant CBA/J mice mated with DBA/2 male mice as a model of spontaneous abortion and FGR were randomly divided into the control and CTRP6 groups. In the CTRP6 group, the mice were intravenously administered CTRP6 on days 4.5 and 6.5 post-conception (dpc). The abortion rate and fetal and placental weights on 14.5 dpc were examined. Remodeling of the spiral artery was also assessed.

RESULTS: The abortion rate in the CTRP6 group (13%) was reduced compared to the control group (21%), but there was no statistical difference. The placental and fetal weights in the CTRP6 group were also heavier than those in the control (P < 0.05). Moreover, the thickness of the blood vessel wall in the CTRP6 group was significantly thinner than that in the control (P < 0.05) and comparable to that in the non-abortion model (CBA/J x BALB). The ratio of the inner-per-the-outer diameter of the spiral artery increased more in the CTRP6 group than that in the control (P < 0.05). As well, the Th1/Th2 cytokine ratio was significantly reduced by CTRP6 treatment.

CONCLUSIONS: Taken together, the supplementation with a protein that regulates the alternative complement pathway in vivo improves FGR and promotes spiral artery remodeling in a mouse model of miscarriage and FGR.

PMID:35907048 | DOI:10.1007/s10815-022-02582-1

J Neurol. 2022 Jul 30. doi: 10.1007/s00415-022-11304-7. Online ahead of print.

ABSTRACT

BACKGROUND: Hyperammonaemia is a recognised complication of antiseizure treatment but risk factors leading to individual patient susceptibility and outcome remain unclear.

OBJECTIVE: To identify risk factors for hyperammonaemia and investigate the impact of its management on clinical outcomes.

METHODS: We carried out a retrospective observational study of adults with epilepsy who had ammonia tested over a 3-year period. Hyperammonaemia was defined as ammonia level > 35 μmol/L. Patients were classified into two groups: hyperammonaemic and non-hyperammonaemic. Association analyses and linear regression analysis were used to identify risk factors for hyperammonaemia.

RESULTS: We reviewed 1002 ammonia requests in total and identified 76 people with epilepsy who had ammonia concentration measured, including 26 with repeated measurements. 59/76 (78%) were found to have hyperammonaemia. There was borderline statistical significance of hyperammonaemia being less common in patients with an established monogenic/metabolic condition than in those with structural or cryptogenic epilepsy (P = 0.05). Drug resistance, exposure to stiripentol and oxcarbazepine were identified as risk factors for hyperammonaemia. We found a dose-dependent association between valproate and hyperammonaemia (P = 0.033). Clinical symptoms were reported in 22/59 (37%) of the hyperammonaemic group. Improved clinical outcomes with concurrent decrease in ammonia concentration were seen in 60% of patients following treatment adjustment.

CONCLUSIONS: Drug resistance and exposure to stiripentol, oxcarbazepine or high-dose valproate are associated with an increased risk of hyperammonaemia. Clinicians should consider symptoms related to hyperammonaemia in patients on high-dose valproate or multiple antiseizure treatments. Prompt identification of hyperammonaemia and subsequent treatment adjustments can lead to improved clinical outcomes.

PMID:35907043 | DOI:10.1007/s00415-022-11304-7

J Exp Orthop. 2022 Jul 30;9(1):74. doi: 10.1186/s40634-022-00507-6.

ABSTRACT

PURPOSE: Certain types of repetitive sub-maximal knee loading cause microfatigue damage in the human anterior cruciate ligament (ACL) that can accumulate to produce macroscopic tissue failure. However, monitoring the progression of that ACL microfatigue damage as a function of loading cycles has not been reported. To explore the fatigue process, a confocal laser endomicroscope (CLEM) was employed to capture sub-micron resolution fluorescence images of the tissue in situ. The goal of this study was to quantify the in situ changes in ACL autofluorescence (AF) signal intensity and collagen microstructure as a function of the number of loading cycles.

METHODS: Three paired and four single cadaveric knees were subjected to a repeated 4 times bodyweight landing maneuver known to strain the ACL. The paired knees were used to compare the development of ACL microfatigue damage on the loaded knee after 100 consecutive loading cycles, relative to the contralateral unloaded control knee, through second harmonic generation (SHG) and AF imaging using confocal microscopy (CM). The four single knees were used for monitoring progressive ACL microfatigue damage development by AF imaging using CLEM.

RESULTS: The loaded knees from each pair exhibited a statistically significant increase in AF signal intensity and decrease in SHG signal intensity as compared to the contralateral control knees. Additionally, the anisotropy of the collagen fibers in the loaded knees increased as indicated by the reduced coherency coefficient. Two out of the four single knee ACLs failed during fatigue loading, and they exhibited an order of magnitude higher increase in autofluorescence intensity per loading cycle as compared to the intact knees. Of the three regions of the ACL – proximal, midsubstance and distal – the proximal region of ACL fibers exhibited the highest AF intensity change and anisotropy of fibers.

CONCLUSIONS: CLEM can capture changes in ACL AF and collagen microstructures in situ during and after microfatigue damage development. Results suggest a large increase in AF may occur in the final few cycles immediately prior to or at failure, representing a greater plastic deformation of the tissue. This reinforces the argument that existing microfatigue damage can accumulate to induce bulk mechanical failure in ACL injuries. The variation in fiber organization changes in the ACL regions with application of load is consistent with the known differences in loading distribution at the ACL femoral enthesis.

PMID:35907038 | DOI:10.1186/s40634-022-00507-6

Environ Manage. 2022 Jul 30. doi: 10.1007/s00267-022-01675-y. Online ahead of print.

ABSTRACT

Hazardous waste pollutes the air, soil, and water and adversely affects human health if not disposed of safely. Analysis of the efficiency of hazardous waste disposal is essential to sustainable development. This paper uses the three-stage super-efficiency Data Envelopment Analysis model to measure the efficiency of 28 EU countries from 2004 to 2016. To ensure the reliability of the results, the article utilizes a one-way ANOVA statistical test to verify whether DEA results vary significantly across various EU countries. This article discusses “how inputs and outputs can be adjusted to eliminate inefficiencies” to suggest a targeted improvement. The third stage supper efficiency DEA results shows that the efficiency varies significantly across different EU countries. The main reasons for the low efficiency are high generated hazardous waste, management expenditure, greenhouse gas emissions, and inadequate waste disposal volume. Targeted proposals from three aspects are given for policymakers in EU countries: Build a resource recycling system to reduce hazardous waste. Establish a sound fee management system to reduce expenses. Optimization of disposal technology to improve incineration efficiency.

PMID:35907030 | DOI:10.1007/s00267-022-01675-y

Skeletal Radiol. 2022 Jul 30. doi: 10.1007/s00256-022-04108-3. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the validity and reliability of the calf injury classification system proposed by the Olympic Park group which focuses on connective tissue structure integrity on MRI.

MATERIALS AND METHODS: A retrospective study analysing calf muscle group injuries in an English Premiership professional rugby union club using the MRI classification proposed by the Olympic Park group. Classification on MRI examinations of 28 calf injuries sustained over a 6-year period was performed by three independent musculoskeletal radiologists to determine the inter-observer variability and correlation of the grade of injury with return-to-full-training (RTFT) time.

RESULTS: RTFT time ranged from 5 to 110 days (mean = 40.1, SD = 26.4) following calf muscle injury. The Olympic Park classification injury grade demonstrated moderate to strong correlation with RTFT time (Spearman’s rank correlation coefficient, 0.661-0.715, p < 0.01). RTFT time was statistically different between different injury grades (one-way ANOVA, p < 0.01). Inter-observer agreement of the overall grade between radiologist pairs was fair to moderate (weighted kappa 0.406-0.583).

CONCLUSION: The Olympic Park classification system demonstrates moderate to strong correlation with time to RTFT following calf injury. Inter-observer reliability is fair to moderate.

PMID:35907017 | DOI:10.1007/s00256-022-04108-3