Nevin Manimala

Orphanet J Rare Dis. 2023 Nov 6;18(1):346. doi: 10.1186/s13023-023-02965-2.

ABSTRACT

BACKGROUND: Little is known about employment status, occupation, and disposable income in adults with NF1.

METHODS: From the Danish National Patient Registry and database of two national Centers for Rare Diseases, we identified 1469 adults with NF1, who were matched to 11,991 randomly selected population comparisons on sex and birth year and month. Annual information on employment, occupation and disposable income was ascertained from national registries in 1980-2019.

RESULTS: Adults with NF1 had a lower odds ratio (OR) for employment [OR 0.71, 95% confidence interval (CI) 0.61-0.83] and higher OR for health-related unemployment (OR 2.94, 95% CI 2.16-3.96) at age 30 years than population comparisons, which persisted at age 40 and 50 years. Somatic diagnoses were associated with a higher OR for health-related unemployment in adults with NF1 than in the population comparisons. Adults with NF1 had a slightly lower disposable income, with a 14% (0.82-0.89) reduction observed among the youngest birth cohort. Furthermore, adults with NF1 were less likely to be in a high skilled occupation at ages 30, 40 and 50 years.

CONCLUSION: Adults with NF1 have a lower employment rate, which was mainly due to health-related reasons and a slightly lower disposable income than adults without NF1. Thus, anticipation guidance for employment should be part of the management of NF1 families.

PMID:37932779 | DOI:10.1186/s13023-023-02965-2

Subst Abuse Treat Prev Policy. 2023 Nov 6;18(1):64. doi: 10.1186/s13011-023-00577-4.

ABSTRACT

BACKGROUND: Opioid-related overdose deaths remain a common cause of death in many settings, and opioid maintenance treatment is evidence-based for the treatment of opioid use disorders. However, access to such treatment varies and is limited in many settings.

METHODS: The present study examines the longitudinal effects of a regional patient choice reform which substantially increased availability to opioid maintenance treatment in one Swedish county, starting from 2014. A previous follow-up, limited in time, indicated a possible effect on mortality from this intervention, demonstrating a lower increase in overdose deaths than in counties without this reform. The present study follows overdose deaths through 2021, and compares the intervention county to the remaining parts in the country, using death certificate statistics from the national causes of death register.

RESULTS: The present study does not demonstrate any significant difference in the development of overdose mortality in the county where this reform substantially expanded treatment access, compared to other counties in the country.

CONCLUSIONS: The study underlines the importance to maintain extensive efforts against overdose deaths over and above the treatment of opioid use disorders, such as low-threshold provision of opioid antidotes or other interventions specifically addressing overdose risk behaviors.

PMID:37932776 | DOI:10.1186/s13011-023-00577-4

Trials. 2023 Nov 6;24(1):709. doi: 10.1186/s13063-023-07650-0.

ABSTRACT

BACKGROUND: Bronchopulmonary dysplasia (BPD), an inflammatory-mediated chronic lung disease, is common in extremely preterm infants born before 28 weeks’ gestation and is associated with an increased risk of adverse neurodevelopmental and respiratory outcomes in childhood. Effective and safe prophylactic therapies for BPD are urgently required. Systemic corticosteroids reduce rates of BPD in the short term but are associated with poorer neurodevelopmental outcomes if given to ventilated infants in the first week after birth. Intratracheal administration of corticosteroid admixed with exogenous surfactant could overcome these concerns by minimizing systemic sequelae. Several small, randomized trials have found intratracheal budesonide in a surfactant vehicle to be a promising therapy to increase survival free of BPD. The primary objective of the PLUSS trial is to determine whether intratracheal budesonide mixed with surfactant increases survival free of bronchopulmonary dysplasia (BPD) at 36 weeks’ postmenstrual age (PMA) in extremely preterm infants born before 28 weeks’ gestation.

METHODS: An international, multicenter, double-blinded, randomized trial of intratracheal budesonide (a corticosteroid) mixed with surfactant for extremely preterm infants to increase survival free of BPD at 36 weeks’ postmenstrual age (PMA; primary outcome). Extremely preterm infants aged < 48 h after birth are eligible if (1) they are mechanically ventilated, or (2) they are receiving non-invasive respiratory support and there is a clinical decision to treat with surfactant. The intervention is budesonide (0.25 mg/kg) mixed with poractant alfa (200 mg/kg first intervention, 100 mg/kg if second intervention), administered intratracheally via an endotracheal tube or thin catheter. The comparator is poractant alfa alone (at the same doses). Secondary outcomes include the components of the primary outcome (death, BPD prior to or at 36 weeks’ PMA), and potential systemic side effects of corticosteroids. Longer-term outcomes will be published separately, and include cost-effectiveness, early childhood health until 2 years of age, and neurodevelopmental outcomes at 2 years of age (corrected for prematurity).

STATISTICAL ANALYSIS PLAN: A sample size of 1038 infants (519 in each group) is required to provide 90% power to detect a relative increase in survival free of BPD of 20% (an absolute increase of 10%), from the anticipated event rate of 50% in the control arm to 60% in the intervention (budesonide) arm, alpha error 0.05. To allow for up to 2% of study withdrawals or losses to follow-up, PLUSS aimed to enroll a total of 1060 infants (530 in each arm). The binary primary outcome will be reported as the number and percentage of infants who were alive without BPD at 36 weeks’ PMA for each randomization group. To estimate the difference in risk (with 95% CI), between the treatment and control arms, binary regression (a generalized linear multivariable model with an identity link function and binomial distribution) will be used. Along with the primary outcome, the individual components of the primary outcome (death, and physiological BPD at 36 weeks’ PMA), will be reported by randomization group and, again, binary regression will be used to estimate the risk difference between the two treatment groups for survival and physiological BPD at 36 weeks’ PMA.

PMID:37932774 | DOI:10.1186/s13063-023-07650-0

Microb Cell Fact. 2023 Nov 6;22(1):228. doi: 10.1186/s12934-023-02238-4.

ABSTRACT

BACKGROUND: Mycosynthesis of silver nanoparticles (SNPs) offers a safe, eco-friendly, and promising alternative technique for large-scale manufacturing. Our study might be the first report that uses mycelial filtrate of an endophytic fungus, Aspergillus flavipes, for SNPs production under optimal conditions as an antimicrobial agent against clinical multidrug-resistant (MDR) wound pathogens.

RESULTS: In the present study, among four different endophytic fungi isolated from leaves of Lycium shawii, the only one isolate that has the ability to mycosynthesize SNPs has been identified for the first time as Aspergillus flavipes AUMC 15772 and deposited in Genebank under the accession number OP521771. One variable at a time (OVAT) and Plackett Burman design (PBD) were conducted for enhancing the production of mycosynthesized SNPs (Myco-SNPs) through optimization using five independent variables. The overall optimal variables for increasing the mycosynthesis of SNPs from mycelial filtrate of A. flavipes as a novel endophytic fungus were a silver nitrate concentration of 2 mM, a pH of 7.0, an incubation time of 5 days, and a mycelial filtrate concentration of 30% in dark conditions. UV-visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FT-IR), X-ray spectroscopy (XRD), Transmission electron microscopy (TEM), and Selected-Area Electron Diffraction (SAED) patterns were used to characterize Myco-SNPs, which showed the peak of absorbance at 420 nm, and FTIR showed the bands at 3426.44, 2923.30, 1681.85, 1552.64, and 1023.02 cm-1, respectively, which illustrated the presence of polyphenols, hydroxyl, alkene, nitro compounds, and aliphatic amines, respectively. The XRD pattern revealed the formation of Myco-SNPs with good crystal quality at 2θ = 34.23° and 38.18°. The TEM image and SAED pattern show the spherical crystalline shape of Myco-SNPs with an average size of 6.9232 nm. High antibacterial activity of Myco-SNPs was recorded against MDR wound pathogens as studied by minimum inhibitory concentrations ranging from 8 to 32 µg/mL, time kill kinetics, and post-agent effects. Also, in vitro cell tests indicated that Myco-SNPs support the cell viability of human skin fibroblast cells as a nontoxic compound.

CONCLUSION: The obtained results revealed the successful production of Myco-SNPs using the mycelial filtrate of A. flavipes, which may be a promising nontoxic alternative candidate for combating MDR wound pathogens.

PMID:37932769 | DOI:10.1186/s12934-023-02238-4

BMC Womens Health. 2023 Nov 6;23(1):573. doi: 10.1186/s12905-023-02710-8.

ABSTRACT

BACKGROUND: Menstruation, especially the menstrual cycle, is a vital sign for female adolescent health and maintaining menstrual hygiene is of utmost importance for menstruating girls and women. However, menstrual hygiene and management are issues that have not received adequate attention. Therefore, the present study aimed to explore spatial patterns of menstrual hygiene practices in India and to identify their socioeconomic and demographic determinants among women aged 15-24 years.

METHODS: The study utilized data from the fifth round of the National Family Health Survey (NFHS-5) conducted during 2019-21 in India. The analysis was limited to 241,180 women aged 15-24 years. The statistical methods range from multinomial logistic regression, spatial autocorrelation in terms of Moran’s I statistics, to spatial regression in order to understand the spatial dependence and clustering in different methods of menstrual practices across the districts of India.

RESULTS: Almost half of the respondents (49.8 percent) reported using hygienic methods of bloodstain protection, while 22.7 percent still relied on unhygienic methods and 27.5 percent reported using both hygienic and unhygienic methods during their menstruation. Factors like age, place of residence, caste, religion, education, wealth index and toilet facility were found to be significantly associated with the use of unhygienic and both methods. It was also observed that the percentage of women practicing hygienic methods was predominantly higher in the Southern region. On the other hand, states like Madhya Pradesh and Bihar appeared to be hotspots for unhygienic menstrual practices. The univariate Moran’s I value for unhygienic and both methods were 0.722 and 0.596, respectively, depicting high spatial autocorrelation across districts in India. In spatial regression, rural residence, illiteracy, poverty, and no toilet facility were found to be statistically significant predictors of the use of unhygienic method and both methods.

CONCLUSION: Young women should be educated about the importance of menstrual hygiene practices and the physiological consequences of unhygienic practices. Furthermore, interventions should target socio-economically disadvantaged women to increase the use of sanitary napkins.

PMID:37932760 | DOI:10.1186/s12905-023-02710-8

BMC Med Inform Decis Mak. 2023 Nov 6;23(1):250. doi: 10.1186/s12911-023-02349-3.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) in pregnancy is a major cause of maternal morbidity and death. The use of low-molecular-weight heparin (LMWH), despite being the standard of care to prevent VTE, comes with some challenges. Shared decision-making (SDM) interventions are recommended to support patients and clinicians in making preference-sensitive decisions. The quality of the SDM process has been widely assessed with the decisional conflict scale (DCS). Our aim is to report participants’ perspectives of each of the components of an SDM intervention (DASH-TOP) in relation to the different subscales of the DCS.

METHODS: Design: A convergent, parallel, mixed-methods design.

PARTICIPANTS: The sample consisted of 22 health care professionals, students of an Applied Clinical Research in Health Sciences (ICACS) master program.

INTERVENTION: We randomly divided the participants in three groups: Group 1 received one component (evidence -based information), Group 2 received two components (first component and value elicitation exercises), and Group 3 received all three components (the first two and a decision analysis recommendation) of the SDM intervention.

ANALYSIS: For the quantitative strand, we used a non-parametric test to analyze the differences in the DCS subscales between the three groups. For the qualitative strand, we conducted a content analysis using the decisional conflict domains to deductively categorize the responses.

RESULTS: Groups that received more intervention components experienced less conflict and better decision-making quality, although the differences between groups were not statistically significant. The decision analysis recommendation improved the efficacy with the decision-making process, however there are some challenges when implementing it in clinical practice. The uncertainty subscale showed a high decisional conflict for all three groups; contributing factors included low certainty of the evidence-based information provided and a perceived small effect of the drug to reduce the risk of a VTE event.

CONCLUSIONS: The DASH-TOP intervention reduced decisional conflict in the decision -making process, with decision analysis being the most effective component to improve the quality of the decision. There is a need for more implementation research to improve the delivery of SDM interventions in the clinical encounter.

PMID:37932759 | DOI:10.1186/s12911-023-02349-3

J Orthop Surg Res. 2023 Nov 7;18(1):839. doi: 10.1186/s13018-023-04179-5.

ABSTRACT

OBJECTIVES: The OPG/RANKL signal pathway was important regulation mechanism of bone remodeling cycle, but the effect of osteoprotegerin (OPG) and RANKL in osteoporosis was uncertain. We did a systematic review with meta-analysis to assess the association between serum OPG/RANKL and osteoporosis.

METHODS: The systematic search, data extraction, critical appraisal, and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Randomized controlled studies were searched in PubMed, OvidMedline, Embase (1946 to present). Standard mean difference (SMD), and associated credible interval (CI) were calculated using RevMan statistical software to assess the continuous data. Heterogeneity in studies was measured by I² values. Subgroup analysis was performed based on different bone turnover.

RESULTS: A total of 5 randomized controlled studies met the inclusion criteria. Both OPG and RANKL had no significant differences between the osteoporosis and control group, and the statistical heterogeneity was high in meta-analysis. However, RANKL had significant differences between the osteoporosis group with low bone turnover and control group (SMD = – 1.17; 95% CI – 1.77 to 0.57; P value < 0.01) in subanalysis. Furthermore, the OPG/RANKL ratio was significant lower in the osteoporosis group than in the control group (SMD = – 0.29; 95% CI – 0.57 to – 0.02; P value < 0.05), and the statistical heterogeneity was very low (Chi² = 0.20, P = 0.66, I² = 0%).

CONCLUSIONS: Our meta-analysis study supported OPG and RANKL were important modulatory factors of bone formation and resorption in bone turnover, respectively. Although the serum level of both OPG and RANKL were not associated with osteoporosis, but the OPG/RANKL ratio was associated with osteoporosis. In future, standardizing the test method and unit was good to clinical application.

PMID:37932757 | DOI:10.1186/s13018-023-04179-5

Microb Cell Fact. 2023 Nov 7;22(1):229. doi: 10.1186/s12934-023-02240-w.

ABSTRACT

Cyanobacteria are a potential source of promising secondary metabolites with different biological activities, including antibacterial, antiviral, antifungal, antiprotozoal, and anticancer activities. To combat the emergence of antibiotic resistance, there is an urgent requirement for new drugs, and cyanobacteria metabolites can constitute alternative new antibacterial medication. The chemical complexity of their exopolysaccharides indicates that they have the potential to be bioactive molecules with many biological activities. The present study aimed to produce and optimise a novel alginate polymer from a newly isolated cyanobacterium, S. algini MNE ON864447, in addition to its promising antibacterial activity. We successfully isolated a new cyanobacterium strain, S. algini MNE ON864447 from the Nile River, which produces alginate as an extracellular polymeric substance. The isolated cyanobacterial alginate was identified using a set of tests, including FTIR, TLC, HPLC, GC-MS, and ¹H NMR. Plackett-Burman statistical design showed that working volume (X1), the incubation period (X2), and inoculum size (X3) are the most significant variables affecting the production of alginate. The highest alginate production (3.57 g/L) was obtained using 4% inoculum size in 400 mL medium/L conical flask after 20 days of the incubation period. The extracted alginate showed potent antibacterial activity against both Gram-negative and Gram-positive bacteria and Streptococcus mutants (NCTC10449) are the most sensitive tested pathogen for purified cyanobacterial alginate with inhibition zone diameters of 34 ± 0.1 mm at 10 mg/mL of purified alginate while Vibro cholera (NCTC 8021) the lowest sensitive one and showed inhibition zone diameters of 22.5 ± 0.05 mm at the same cyanobacterial alginate concentration. This antibacterial activity is a critical step in the development of antibacterial drugs and presents a new challenge to fight against multi-resistant bacteria.

PMID:37932753 | DOI:10.1186/s12934-023-02240-w

BMC Public Health. 2023 Nov 7;23(1):2177. doi: 10.1186/s12889-023-17008-5.

ABSTRACT

BACKGROUND: The relation of social deprivation with single cardiometabolic disease (CMD) was widely investigated, whereas the association with cardiometabolic multi-morbidity (CMM), defined as experiencing more than two CMDs during the lifetime, is poorly understood.

METHODS: We analyzed 345,417 UK Biobank participants without any CMDs at recruitment to study the relation between social deprivation and four CMDs including type II diabetes (T2D), coronary artery disease (CAD), stroke and hypertension. Social deprivation was measured by Townsend deprivation index (TDI), and CMM was defined as occurrence of two or more of the above four diseases. Multivariable Cox models were performed to estimate hazard ratios (HRs) per one standard deviation (SD) change and in quartile (Q1-Q4, with Q1 as reference), as well as 95% confidence intervals (95% CIs).

RESULTS: During the follow up, 68,338 participants developed at least one CMD (median follow up of 13.2 years), 16,225 further developed CMM (median follow up of 13.4 years), and 18,876 ultimately died from all causes (median follow up of 13.4 years). Compared to Q1 of TDI (lowest deprivation), the multivariable adjusted HR (95%CIs) of Q4 (highest deprivation) among participants free of any CMDs was 1.23 (1.20 ~ 1.26) for developing one CMD, 1.42 (1.35 ~ 1.48) for developing CMM, and 1.34 (1.27 ~ 1.41) for all-cause mortality. Among participants with one CMD, the adjusted HR (95%CIs) of Q4 was 1.30 (1.27 ~ 1.33) for developing CMM and 1.34 (1.27 ~ 1.41) for all-cause mortality, with HR (95%CIs) = 1.11 (1.06 ~ 1.16) for T2D patients, 1.07 (1.03 ~ 1.11) for CAD patients, 1.07 (1.00 ~ 1.15) for stroke patients, and 1.24 (1.21 ~ 1.28) for hypertension patients. Among participants with CMM, TDI was also related to the risk of all-cause mortality (HR of Q4 = 1.35, 95%CIs 1.28 ~ 1.43).

CONCLUSIONS: We revealed that people living with high deprived conditions would suffer from higher hazard of CMD, CMM and all-cause mortality.

PMID:37932741 | DOI:10.1186/s12889-023-17008-5

Ann Gen Psychiatry. 2023 Nov 6;22(1):45. doi: 10.1186/s12991-023-00477-8.

ABSTRACT

BACKGROUND: There is a critical need for effective treatment of the core symptoms of autism spectrum disorder (ASD). The purinergic antagonist suramin may improve core symptoms through restoration of normal mitochondrial function and reduction of neuro-inflammation via its known antagonism of P2X and P2Y receptors. Nonclinical studies in fragile X knockout mice and the maternal immune activation model support these hypotheses.

METHODS: We conducted a 14 week, randomized, double-blind, placebo-controlled proof -of-concept study (N = 52) to test the efficacy and safety of suramin intravenous infusions in boys aged 4-15 years with moderate to severe ASD. The study had 3 treatment arms: 10 mg/kg suramin, 20 mg/kg suramin, and placebo given at baseline, week 4, and week 8. The Aberrant Behavior Checklist of Core Symptoms (ABC-Core) (subscales 2, 3, and 5) was the primary endpoint and the Clinical Global Impressions-Improvement (CGI-I) was a secondary endpoint.

RESULTS: Forty-four subjects completed the study. The 10 mg/kg suramin group showed a greater, but statistically non-significant, numeric improvement (- 12.5 ± 3.18 [mean ± SE]) vs. placebo (- 8.9 ± 2.86) in ABC-Core at Week 14. The 20 mg/kg suramin group did not show improvement over placebo. In exploratory analyses, the 10 mg/kg arm showed greater ABC Core differences from placebo in younger subjects and among those with less severe symptoms. In CGI-I, the 10 mg/kg arm showed a statistically significant improvement from baseline (2.8 ± 0.30 [mean ± SE]) compared to placebo (1.7 ± 0.27) (p = 0.016). The 20 mg/kg arm had a 2.0 ± 0.28 improvement in CGI-I, which was not statistically significant compared to placebo (p = 0.65).

CONCLUSION: Suramin was generally safe and well tolerated over 14 weeks; most adverse events were mild to moderate in severity. Trial Registration Registered with the South African Health Authority, registration number DOH-27-0419-6116.

CLINICALTRIALS: Gov registration ID is NCT06058962, last update posted 2023-09-28.

PMID:37932739 | DOI:10.1186/s12991-023-00477-8