Nevin Manimala

Acta Vet Hung. 2022 Nov 8. doi: 10.1556/004.2022.00035. Online ahead of print.

ABSTRACT

The effects of clinoptilolite on milk copper (Cu), lead (Pb), zinc (Zn), cadmium (Cd) and iron (Fe) concentrations, proinflammatory cytokine responses, oxidative stress status, whole blood cell counts and liver and kidney functions were investigated in dairy cows exhibiting no signs of any kind of toxicity. Clinoptilolite was added to the feed at a dose of 200 mg kg-1 body weight in the clinoptilolite-treated group (n = 14), but was not added to the feed in the control group (n = 7). In the milk samples (n = 21) collected before the experiment, the Cu, Pb, Zn, Cd and Fe values were 0.021 ± 0.020, 0.104 ± 0.01, 3.42 ± 0.32, <0.000, 0.56 ± 0.34 ppm, respectively. At the end of the experiment (30th day), among the elements measured in milk samples collected from the clinoptilolite-treated group, only the Pb value (0.076 ± 0.01) was lower than the 0-day value of the clinoptilolite-treated group (0.104 ± 0.01) and the 30th-day value of the control group (0.105 ± 0.01) was found to be statistically lower. Changes determined at the end of clinoptilolite application in serum superoxide dismutase (SOD), malondialdehyde (MDA), albumin, glucose, urea and urine creatinine/urine total protein (uCr/uTP) values, which were interpreted as the effect of lead exposure before the trial, were evaluated as the positive effect of clinoptilolite. It was concluded that the addition of clinoptilolite to the feed in dairy cows caused a significant decrease in the amount of Pb in milk, and positive changes in the parameters related to oxidative stress in serum and in parameters related to renal function.

PMID:36350569 | DOI:10.1556/004.2022.00035

J Am Med Inform Assoc. 2022 Nov 9:ocac213. doi: 10.1093/jamia/ocac213. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine if the Conexion digital localized health information resource about diabetes and depression could increase patient activation among Hispanic low-income adults.

MATERIALS AND METHODS: A nonblinded randomized controlled trial was conducted (NCT03984929). Participants at least 18 years old living in Washington Heights/Inwood, New York, were recruited from the community between July 2019 and August 2020 and randomized 1:1 to either the intervention group (localization of MedlinePlus resources customized with community components) or the control group (no localized community components). The primary outcome, patient activation, and secondary outcomes, knowledge, self-efficacy, and behavior change, were collected through surveys at 1-month follow-up.

RESULTS: Of the 134 participants recruited, 50.7% (n = 68) completed the 1-month follow-up. We found no statistically significant differences in the sociodemographic and baseline characteristics between those who missed the 1-month survey and those who completed it. No significant differences were observed in patient activation at 1-month. However, patient activation among all participants (n = 68) significantly increased (P = .048). Statistically significant improvements were also found in self-efficacy (P &lt; .03). In multivariate analysis, birth country outside the United States and higher self-rated attachment to the community emerged as significant predictors of higher patient activation scores.

DISCUSSION: While the trial did not detect significant differences between groups, all participants demonstrated increased patient activation scores and improved secondary outcomes. While other factors may have contributed to this increase, our study suggests that access to carefully selected high-quality health information materials delivered digitally in the context of a community may result in improvements comparable to localized content in a hard-to-reach urban Hispanic population.

CONCLUSIONS: Our study highlights the potential of making carefully selected digital information accessible to hard-to-reach communities.

PMID:36350567 | DOI:10.1093/jamia/ocac213

Brain. 2022 Nov 9:awac421. doi: 10.1093/brain/awac421. Online ahead of print.

ABSTRACT

Leber hereditary optic neuropathy (LHON) is an important example of mitochondrial blindness with the m.11778G > A mutation in the MT-ND4 gene being the most common disease-causing mitochondrial DNA (mtDNA) variant worldwide. The REFLECT phase 3 pivotal study is a randomized, double-masked, placebo-controlled trial investigating the efficacy and safety of bilateral intravitreal injection of lenadogene nolparvovec in patients with a confirmed m.11778G > A mutation, using a recombinant adeno-associated virus vector 2, serotype 2 (rAAV2/2-ND4). The first-affected eye received gene therapy; the fellow (affected/not-yet-affected) eye was randomly injected with gene therapy or placebo. The primary endpoint was the difference in change from baseline of best-corrected visual acuity (BCVA) in second-affected/not-yet-affected eyes treated with lenadogene nolparvovec versus placebo at 1.5 years post-treatment, expressed in logarithm of the minimal angle of resolution (LogMAR). Forty-eight patients were treated bilaterally and 50 unilaterally. At 1.5 years, the change from baseline in BCVA was not statistically different between second-affected/not-yet-affected eyes receiving lenadogene nolparvovec and placebo (primary endpoint). A statistically significant improvement in BCVA was reported from baseline to 1.5 years in lenadogene nolparvovec-treated eyes: -0.23 LogMAR for the first-affected eyes of bilaterally treated patients (p < 0.01); and -0.15 LogMAR for second-affected/not-yet-affected eyes of bilaterally treated patients and the first-affected eyes of unilaterally treated patients (p < 0.05). The mean improvement in BCVA from nadir to 1.5 years was -0.38 (0.052) LogMAR and -0.33 (0.052) LogMAR in first-affected and second-affected/not-yet-affected eyes treated with lenadogene nolparvovec, respectively (bilateral treatment group). A mean improvement of -0.33 (0.051) LogMAR and -0.26 (0.051) LogMAR was observed in first-affected lenadogene nolparvovec-treated eyes and second-affected/not-yet-affected placebo-treated eyes, respectively (unilateral treatment group). The proportion of patients with one or both eyes on-chart at 1.5 years was 85.4% and 72.0% for bilaterally and unilaterally treated patients, respectively. The gene therapy was well tolerated, with no systemic issues. Intraocular inflammation, which was mostly mild and well controlled with topical corticosteroids, occurred in 70.7% of lenadogene nolparvovec-treated eyes versus 10.2% of placebo-treated eyes. Among eyes treated with lenadogene nolparvovec, there was no difference in the incidence of intraocular inflammation between bilaterally and unilaterally treated patients. Overall, the REFLECT trial demonstrated an improvement of BCVA in LHON eyes carrying the m.11778G > A mtDNA mutation treated with lenadogene nolparvovec or placebo to a degree not reported in natural history studies and supports an improved benefit/risk profile for bilateral injections of lenadogene nolparvovec relative to unilateral injections.

PMID:36350566 | DOI:10.1093/brain/awac421

Hum Reprod. 2022 Nov 9:deac243. doi: 10.1093/humrep/deac243. Online ahead of print.

ABSTRACT

STUDY QUESTION: Do ovarian hormone changes influence the levels of cell-free or circulating microRNA (cf-miRNA) across the menstrual cycle?

SUMMARY ANSWER: This exploratory study suggests that fluctuations in hormonal levels throughout the menstrual cycle may alter cf-miRNAs levels.

WHAT IS KNOWN ALREADY: cf-miRNA levels vary with numerous pathological and physiological conditions in both males and females and are regulated by exogenous and endogenous factors, including hormones.

STUDY DESIGN, SIZE, DURATION: A prospective, monocentric study was conducted between March and November 2021. Since this was a pilot study, the sample size was based on feasibility as well as previous similar human studies conducted in different tissues. A total of 20 participants were recruited for the study.

PARTICIPANTS/MATERIALS, SETTING, METHODS: We conducted an exploratory study where blood samples were collected from 16 eumenorrheic females in the early follicular phase, the ovulation phase and the mid-luteal phase of the menstrual cycle. The levels of oestrogen, progesterone, LH and FSH were measured in serum by electrochemiluminescence. The levels of 174 plasma-enriched miRNAs were profiled using a PCR-based panel, including stringent internal and external controls to account for the potential differences in RNA extraction and reverse-transcription stemming from low-RNA input samples.

MAIN RESULTS AND THE ROLE OF CHANCE: This exploratory study suggests that cf-miRNAs may play an active role in the regulation of the female cycle by mediating the expression of genes during fluctuating hormonal changes. Linear mixed-models, adjusted for the relevant variables, showed associations between phases of the menstrual cycle, ovarian hormones and plasma cf-miRNA levels. Validated gene targets of the cf-miRNAs varying with the menstrual cycle were enriched within female reproductive tissues and are primarily involved in cell proliferation and apoptosis.

LARGE SCALE DATA: All relevant data are available from the Mendeley database: LEGER, Bertrand (2022), ‘MiRNA and menstrual cycle’, Mendeley Data, V1, doi: 10.17632/2br3zp79m3.1.

LIMITATIONS, REASONS FOR CAUTION: Our study was conducted on a small participant cohort. However, it was tightly controlled for endogenous and exogenous confounders, which is critical to ensure robust and reproducible cf-miRNA research. Both adjusted and non-adjusted P-values are presented throughout the article.

WIDER IMPLICATIONS OF THE FINDINGS: Measures of ovarian hormones should be rigorously included in future studies assessing cf-miRNA levels in females and used as time-varying confounders. Our results reinforce the importance of accounting for female-specific biological processes in physiology research by implementing practical or statistical mitigation strategies during data collection and analysis.

STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Clinique romande de réadaptation, Sion, Switzerland. S.L. was supported by an Australian Research Council (ARC) Future Fellowship (FT10100278). D.H. was supported by an Executive Dean’s Postdoctoral Research Fellowship from Deakin University. The authors declare no competing interests.

PMID:36350564 | DOI:10.1093/humrep/deac243

Dig Dis Sci. 2022 Nov 9. doi: 10.1007/s10620-022-07741-z. Online ahead of print.

ABSTRACT

INTRODUCTION: Esophageal foreign body impaction (FBI) is a commonly encountered gastrointestinal emergency requiring immediate intervention. Foreign bodies can be composed of food, commonly referred to as a “food bolus” (FB), or other matter (non-food). We aim to conduct systematic review and meta-analysis to compare cap-assisted and conventional endoscopic techniques for removal of esophageal FBI.

METHODS: A comprehensive search technique was utilized to identify studies that used capped endoscopic devices to remove FB or other esophageal foreign bodies. The primary outcomes were the technical success rate, rate of en bloc retrieval, and procedure time. Secondary outcomes were overall adverse events, bleeding, mucosal tears, and perforation.

RESULTS: Seven studies with a total of 1407 patients were included. The mean patient age was 55.3 (SD ± 7.2) years and 44.8% of patients were male. There were two RCTs and five observational studies among the included studies. The technical success rate was significantly higher in the cap-assisted group compared to the conventional group (OR 3.47, CI 1.68-7.168, I² = 0%, p = < 0.001), as well as the en bloc retrieval rate (OR 26.90, CI 17.82-40.60, I² = 0%, p = 0.001). There was a trend towards lower procedural time for the cap-assisted group compared to the conventional group, although the difference did not reach statistical significance (MD – 10.997, CI – 22.78-0.786, I² = 99.9%, p = 0.06). The overall adverse events were significantly lower in the cap-assisted group compared to the conventional group (OR 0.118, CI 0.018-0.792, I² = 81.79%, p = 0.02).

CONCLUSION: The cap-assisted technique has improved efficacy and safety. To confirm these results, larger randomized trials are warranted.

PMID:36350475 | DOI:10.1007/s10620-022-07741-z

Mol Cell Biochem. 2022 Nov 9. doi: 10.1007/s11010-022-04605-y. Online ahead of print.

ABSTRACT

Premature ventricular contractions (PVCs) are the most frequent ventricular arrhythmias in the overall population. PVCs are known to acutely enhance contractility by the post-extrasystolic potentiation phenomenon, but over time persistent PVCs promote PVC-induced cardiomyopathy (PVC-CM), characterized by a reduction of the left ventricular (LV) ejection fraction. Ca²⁺ cycling in myocytes commands muscle contraction and in this process, SERCA2 leads the Ca²⁺ reuptake into the sarcoplasmic reticulum (SR) shaping cytosolic Ca²⁺ signal decay and muscle relaxation. Altered Ca²⁺ reuptake can contribute to the contractile dysfunction observed in PVC-CM. To better understand Ca²⁺ handling using our PVC-CM model (canines with 50% PVC burden for 12 weeks), SR-Ca²⁺ reuptake was investigated by measuring Ca²⁺ dynamics and analyzing protein expression. Kinetic analysis of Ca²⁺ reuptake in electrically paced myocytes showed a ~ 21 ms delay in PVC-CM compared to Sham in intact isolated myocytes, along with a ~ 13% reduction in SERCA2 activity assessed in permeabilized myocytes. Although these trends were not statistically significant between groups using hierarchical statistics, relaxation of myocytes following contraction was significantly slower in PVC-CM vs Sham myocytes. Western blot analyses indicate a 22% reduction in SERCA2 expression, a 23% increase in phospholamban (PLN) expression, and a 50% reduction in PLN phosphorylation in PVC-CM samples vs Sham. Computational analysis simulating a 20% decrease in SR-Ca²⁺ reuptake resulted in a ~ 22 ms delay in Ca²⁺ signal decay, consistent with the experimental result described above. In conclusion, SERCA2 and PLB alterations described above have a modest contribution to functional adaptations observed in PVC-CM.

PMID:36350464 | DOI:10.1007/s11010-022-04605-y

Psychogeriatrics. 2022 Nov 9. doi: 10.1111/psyg.12909. Online ahead of print.

ABSTRACT

BACKGROUND: Geriatric cognitive impairment often occurs in conjunction with depressive symptoms. This study focuses on categorising the Chinese elderly with such co-occurring symptoms into homogeneous groups using latent profile analysis (LPA), a person-centred statistical approach.

METHODS: Information on cognitive function and depressive states of the elderly was extracted from the China Health and Retirement Longitudinal Study. The underlying characteristics were identified by LPA, and based on those findings, differences in demographic characteristics of different subgroups were explored by chi-squared test and analysis of variance.

RESULTS: A total of 6710 Chinese elderly who met the inclusion criteria were selected from the dataset. Four subgroups were identified among this sample by LPA, based on cognitive function associated with depressive symptoms, and named in this study as follows: mild cognitive impairment (n = 3747, 55.84%), moderate cognitive impairment (n = 1306, 19.46%), mild cognitive impairment combined with depressive symptoms (n = 1114, 16.6%), and moderate cognitive impairment combined with depression (n = 543, 8.09%). Age, gender, marital status, and educational level were all significantly different across subgroups (P < 0.001); religious belief and pension mode, however, were not (P > 0.05).

CONCLUSIONS: In the present study, four subgroups of cognitive function combined with depressive symptoms were found in Chinese elderly individuals, and differences in demographic factors were noted between the subgroups. In clinical practise, these findings could help clinical workers identify patients accurately and consider the demographic features of each subgroup when designing medical treatment, care, and rehabilitation programmes for those with cognitive impairment and concomitant depressive symptoms.

PMID:36349873 | DOI:10.1111/psyg.12909

Transfus Med. 2022 Nov 9. doi: 10.1111/tme.12935. Online ahead of print.

ABSTRACT

BACKGROUND: Hepatitis C virus (HCV) can be transmitted by blood transfusion. The aim of this meta-analysis is to estimate the anti-HCV reactive rate and to define the demographic characteristics of blood donors who have potential threats to blood safety in mainland China for nearly 30 years, in order to provide a safe reference for blood transfusion and corresponding guidance for policymakers to increase blood safety.

MATERIALS AND METHODS: Literature reporting the anti-HCV screening reactive rate in Chinese blood donors was identified by systematic searching of four electronic databases from 1991 to 2017. The Preferred Reporting of Items for Systematic Reviews and Meta-Analyses guidelines were strictly followed, and data manipulation and statistical analysis were performed by Stata 15.0.

RESULTS: Our results showed that the post-donation anti-HCV reactive rate was 0.53% (95% confidence interval [CI], 0.51%-0.55%) with a significant variation from 1.58% (95% CI, 1.13%-2.03%) before 1998 to 0.51% (95% CI, 0.48%-0.53%) after 1998 when the Blood Donation Law was implemented in China. In addition, anti-HCV screening reactive rate for family or replacement donors was significantly higher than that in individual voluntary blood donors.

CONCLUSION: Our results indicated that blood centres in China should convert more eligible first-time donors into repeat donors and turn the ‘real family or replacement donors’ into individual voluntary blood donors to reduce the risk of transfusion-transmitted HCV. In the meantime, large surveys should be carried out among volunteer donors from high-risk populations.

PMID:36349871 | DOI:10.1111/tme.12935

Tijdschr Psychiatr. 2022;64(9):604-607.

ABSTRACT

BACKGROUND: In 2018 Jellinek became a smoke free institution. By implementing &lsquo;Jellinek Smoke free&rsquo; in all locations (15), a policy has been implemented to facilitate smoking cessation in clients with a comorbid tobacco use disorder seeking treatment for substance use disorders at Jellinek.

AIM: To investigate whether the implementation of the new policy impacted smoking behaviour of clients in treatment for substance use disorders at Jellinek.

METHOD: Based on data from anonymized client files, changes in smoking behaviour (cessation or reduction) were analysed for clients with other addictions who started treatment in 2016 versus clients who started in 2019 – after the implementation of the new smoke free policy. Comparative analyses were conducted on the population as a whole, per type of treatment (outpatient care, residential care, Minnesota, outreaching care) as well as per type of smoker (light, moderate, heavy).

RESULTS: In the client population as a whole, significantly more people stopped smoking in 2019 (22%) in comparison to 2016 (16%) and there was a trend toward statistical significance with regard to reduction. When a cessation period was part of treatment, significantly more clients stopped and decreased the number of cigarettes a day. Moreover, light and moderate smokers (&le; 20 cigarettes a day) stopped and reduced significantly more in 2019 (32%) than in 2016 (23%). In outpatient care, outreaching care and with heavy smokers (&gt; 20 cigarettes a day), there was no significant difference in percentage of cessation and reduction between 2016 and 2019.

CONCLUSION: After implementing Jellinek Smoke free, significant changes in smoking behaviour occurred in the client population as a whole with a comorbid tobacco use disorder, in treatments where a cessation period was part of treatment as well as with light and moderate smokers.

PMID:36349857

Tijdschr Psychiatr. 2022;64(9):558-565.

ABSTRACT

BACKGROUND: Psychiatric disorders are associated with a more severe course of COVID-19. COVID-19 can also lead to psychiatric symptoms.

AIM: To gain insight into vulnerabilities and protective factors for the course of COVID-19 in a Dutch (neuro)psychiatric population.

METHOD: Patients were divided into three groups: patients with pre-existent mental disorders without and with new (neuro)psychiatric symptoms (NPS) during COVID-19 and patients without pre-existent mental disorders who developed de novo NPS during COVID-19. We summarize the characteristics of each group and compare the subgroups with inferential statistics.

RESULTS: 186 patients were included in the case register. Patients with NPS showed a more severe course of COVID-19. Mortality in patients with NPS was higher in patients with pre-existent mental disorders compared to patients without pre-existent mental disorders. The most frequently reported de novo psychiatric symptoms during COVID-19 were delirium (46-70%), anxiety (53-54%) and insomnia (18-42%).

CONCLUSION: NPS might be an expression of a more severe COVID-19 episode. In patients who developed NPS during COVID-19 we found evidence for a higher mortality risk in patients with pre-existent mental disorders. Extra vigilance for neuropsychiatric symptoms during COVID-19 is warranted.

PMID:36349850