Nevin Manimala

J Clin Psychopharmacol. 2021 Aug 20. doi: 10.1097/JCP.0000000000001465. Online ahead of print.

ABSTRACT

PURPOSE/BACKGROUND: Numerous health authority approvals of esketamine nasal spray, combined with oral antidepressant, to treat depressive symptoms in adults with major depressive disorder and acute suicidal ideation or behavior were based on 2 identically designed, double-blind, phase 3 studies.

METHODS/PROCEDURES: Across both ASPIRE studies (NCT03039192, NCT03097133), patients (N = 456) were randomized to esketamine 84 mg or placebo nasal spray twice weekly for 4 weeks plus comprehensive standard of care, including hospitalization and newly initiated or optimized antidepressant(s). In post hoc analyses of pooled data, changes from baseline at 24 hours after the first dose in Montgomery-Åsberg Depression Rating Scale total score and Clinical Global Impression-Severity of Suicidality-Revised, in the full cohort and in subgroups, were analyzed using analysis of covariance.

FINDINGS/RESULTS: Esketamine plus standard of care demonstrated significantly greater improvement in Montgomery-Åsberg Depression Rating Scale total score versus placebo plus standard of care at 24 hours (least square mean difference [95% confidence interval], -3.8 [-5.75 to -1.89]) and at earlier (4 hours: -3.4 [-5.05 to -1.71]) and later time points (day 25: -3.4 [-5.36 to -1.36]). The between-group difference (95% confidence interval) for change in Clinical Global Impression-Severity of Suicidality-Revised at 24 hours was -0.20 (-0.43 to 0.04) for all patients and -0.31 (-0.61 to -0.01) for those with a history of suicide attempt. Common adverse events (≥20%) during esketamine treatment were dizziness, dissociation, nausea, somnolence, and headache.

IMPLICATIONS/CONCLUSIONS: Esketamine plus comprehensive standard of care rapidly reduces depressive symptoms in patients with major depressive disorder who have acute suicidal ideation or behavior, especially in those with a history of suicide attempt, providing a new treatment option for this particularly ill and vulnerable population.

PMID:34412104 | DOI:10.1097/JCP.0000000000001465

J Occup Environ Med. 2021 Aug 18. doi: 10.1097/JOM.0000000000002357. Online ahead of print.

ABSTRACT

OBJECTIVE: To document Covid-19 sero-prevalence, prior testing, symptom experiences, and risk factors in a sample of community health center (CHC) workers.

METHODS: Descriptive statistics and log-binomial regression were used to analyze an electronic employee survey linked with Covid-19 antibody results. The sample included 378 employees who completed the survey; 325 had complete lab data.

RESULTS: The sero-positivity rate was 15.4%. One third of sero-positive participants had no previous Covid-19 symptoms or were unsure. Working on-site only and/or with direct patient contact was not associated with sero-positivity. Employees in their 20 s were more likely to test positive than employees ages 50+, controlling for sex, race, and region (PR = 2.96; p < .05).

CONCLUSIONS: With CHCs central to Covid-19 response and vaccination efforts, public health messaging should remind CHC workers, especially younger employees, of their risks of community-based exposure.

PMID:34412095 | DOI:10.1097/JOM.0000000000002357

Psychiatr Genet. 2021 Aug 17. doi: 10.1097/YPG.0000000000000296. Online ahead of print.

ABSTRACT

INTRODUCTION: In humans the normal development of cortical regions depends on the complex interactions between a number of proteins that promote the migrations of neuronal precursors from germinal zones and assembly into neuronal laminae. ASTN2 is one of the proteins implicated in such a complex process. Recently it has been observed that ASTN2 also regulates the surface expression of multiple synaptic proteins resulting in a modulation of synaptic activity. Several rare copy number variants (CNVs) in ASTN2 gene were identified in patients with neurodevelopmental disorders (NDDs) including autism spectrum disorders (ASD), attention deficit-hyperactivity disorders and intellectual disability.

METHODS: By using comparative genomic hybridization array technology, we analyzed the genomic profiles of five patients of three unrelated families with NDDs. Clinical diagnosis of ASD was established according to the Statistical Manual of Mental Disorders, Fifth Edition (APA 2013) criteria.

RESULTS: We identified new rare CNVs encompassing ASTN2 gene in three unrelated families with different clinical phenotypes of NDDs. In particular, we identified a deletion of about 70 Kb encompassing intron 19, a 186 Kb duplication encompassing the sequence between the 5′-end and the first intron of the gene and a 205 Kb deletion encompassing exons 6-11.

CONCLUSION: The CNVs reported here involve regions not usually disrupted in patients with NDDs with two of them affecting only the expression of the long isoforms. Further studies will be needed to analyze the impact of these CNVs on gene expression regulation and to better understand their impact on the protein function.

PMID:34412080 | DOI:10.1097/YPG.0000000000000296

Folia Phoniatr Logop. 2021 Aug 19:1-9. doi: 10.1159/000517064. Online ahead of print.

ABSTRACT

INTRODUCTION: The effect of the continuous forced expiration action of players of wind instruments to produce sound, on the eustachian tube functions and the middle-ear resonance frequency (RF), has not been investigated in the literature to date. The aim of this study is to evaluate eustachian tube functions and the middle-ear RF of players of wind instruments.

METHODS: In this prospective case-control clinical study, a study group of 28 players of wind instruments in the orchestra (28 participants, 56 ears) and a control group of 34 volunteers (34 participants, 68 ears) were included. The eustachian function of wind instrument players in a symphony orchestra was measured using an automatic eustachian tube function test in acoustic tympanometry and the RF of the middle ear was determined in multifrequency tympanometry.

RESULTS: There was a statistically significant difference among the musicians, especially in players of woodwind instruments, in terms of dysfunction of the eustachian tubes (p = 0.048). In the musicians, the pre- and postperformance RF mean values for all ears were 925 and 1,020 Hz, respectively, and these were significantly different (p = 0.004).

CONCLUSION: This is the first study to uses multifrequency tympanometry to examine the middle-ear RF and eustachian tube function of wind instrument musicians in an orchestra. Eustachian tube dysfunction was found to be more prominent and a higher RF of the middle ear was seen after a performance, especially in players of wood wind instruments. However, the effect of these on the professional performance of players of wind instruments should be investigated in future work.

PMID:34412053 | DOI:10.1159/000517064

Folia Phoniatr Logop. 2021 Aug 19:1-10. doi: 10.1159/000516225. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this study is quantitative assessment of nasalance for skeletal Class I (normative values), Class II, and III malocclusion in the English language for the North Indian population and to compare the normative values with the nasalance scores obtained from individuals with skeletal Class II and III malocclusion and to evaluate the normative values as a function of gender.

MATERIAL AND METHODS: The study was conducted on a total sample of 200 patients with 100, 50, and 50 in group 1 (control group, Skeletal Class I), group 2 (Skeletal Class II), and group 3 (Skeletal Class III), respectively. ANB angle (anteroposterior angle formed by point A, nasion, and point B) measured on lateral cephalogram was used to categorize the patients into 3 groups. The normative nasalance scores were compared for males and females in the control group. The nasalance scores of skeletal Class II and III subjects were compared to the combined normative scores of the control group. The NasalView was used for the objective assessment of nasalance. Oral syllables (/pa/and/pi/), nasal syllables (/ma/and/mi/), and 3 passages (Zoo passage, Rainbow passage, and Nasal sentences) were used to determine the nasalance scores.

RESULTS: The intragroup comparison of nasalance scores in group 1 showed statistically significant differences for different stimuli. The gender-related comparison showed no statistically significant differences in nasalance scores. The intergroup comparison of nasalance scores for skeletal malocclusion showed no statistically significant differences for different stimuli except statistically significant lower nasalance values for nasal sentences in group 3 compared to the control group.

CONCLUSION: The study concluded that the nasalance scores for nasal sentences in skeletal Class III malocclusion were significantly lower than in the control group and were not statistically significant between the 3 groups for all other stimuli.

PMID:34412052 | DOI:10.1159/000516225

J Mech Behav Biomed Mater. 2021 Aug 12;123:104728. doi: 10.1016/j.jmbbm.2021.104728. Online ahead of print.

ABSTRACT

Artificial intelligence (AI) and machine learning (ML) are fascinating interdisciplinary scientific domains where machines are provided with an approximation of human intelligence. The conjecture is that machines are able to learn from existing examples, and employ this accumulated knowledge to fulfil challenging tasks such as regression analysis, pattern classification, and prediction. The horse biomechanical models have been identified as an alternative tool to investigate the effects of mechanical loading and induced deformations on the tissues and structures in humans. Many reported investigations into bone fatigue, subchondral bone damage in the joints of both humans and animals, and identification of vital parameters responsible for retaining integrity of anatomical regions during normal activities in all species are heavily reliant on equine biomechanical research. Horse racing is a lucrative industry and injury prevention in expensive thoroughbreds has encouraged the implementation of various measurement techniques, which results in massive data generation. ML substantially accelerates analysis and interpretation of data and provides considerable advantages over traditional statistical tools historically adopted in biomechanical research. This paper provides the reader with: a brief introduction to AI, taxonomy and several types of ML algorithms, working principle of a feedforward artificial neural network (ANN), and, a detailed review of the applications of AI, ML, and ANN in equine biomechanical research (i.e. locomotory system function, gait analysis, joint and bone mechanics, and hoof function). Reviewing literature on the use of these data-driven tools is essential since their wider application has the potential to: improve clinical assessments enabling real-time simulations, avoid and/or minimize injuries, and encourage early detection of such injuries in the first place.

PMID:34412024 | DOI:10.1016/j.jmbbm.2021.104728

Vet Microbiol. 2021 Aug 12;261:109190. doi: 10.1016/j.vetmic.2021.109190. Online ahead of print.

ABSTRACT

There has been a tremendous increase in recent years of population-based diagnostic monitoring and surveillance strategies in swine populations. One example is the use of processing fluids (PF) to screen breeding herds for porcine reproductive and respiratory syndrome virus (PRRSV) activity. An important question from practitioners using such methods is on how intensively can the sample be pooled. More specifically, processing fluids of how many litters can be pooled into a single sample for diagnostic testing to preserve a high probability of PRRSV RNA detection at low prevalence situations? The objective of this study was to model the effect of pooling PF samples on the probability of PRRSV RNA detection. For this study, a PRRSV-positive PF field sample with a RT-rtPCR quantification cycle (Cq) value of 28 was selected to represent a litter of 11 pigs with a single viremic piglet. PF samples from a PRRSV-naïve herd were used to perform 6 replications of 8 two-fold serial dilutions of the PRRSV-positive sample, thus modeling the pooling effect (dilution). Each two-fold dilution represented an increase in the number of PRRS-negative pigs in the sample by a factor of 2. Samples were tested for PRRSV RNA by RT-rtPCR and the data was analyzed using linear and probit regression models. There was an average increment of 1.37 points in Ct for each two-fold dilution. The estimated probability of testing positive on RT-rtPCR was 43 %, 80 %, and 95 % when there was a single PRRSv-positive piglet among 784, 492, and 323 PRRSv-negative piglets contributing to the sample respectively. Results from this study support the practice of collecting and aggregating PF samples from multiple litters for PRRSV RNA testing.

PMID:34411996 | DOI:10.1016/j.vetmic.2021.109190

Mar Pollut Bull. 2021 Aug 16;172:112851. doi: 10.1016/j.marpolbul.2021.112851. Online ahead of print.

ABSTRACT

The environmental status of three Intermittently Closed and Open Lakes and Lagoons (ICOLLs) (Manly, Curl Curl and Dee Why Lagoons) in northern Sydney (Australia) were assessed using sedimentary metals. Results identified the highest sedimentary metal enrichment in the Australian central east coast estuaries, with only a moderate ecological risk. A comparison with surficial sediment concentrations from 1996 to 2008 indicated declining metal concentrations, which is largely supported by subsurface metals data. Extensive low-lying areas of the catchments were historically reclaimed by infilling wetlands, which may have resulted in contaminated groundwater influx to the lagoons. An analysis of the sedimentary metals mix in lagoons surrounded by extensive infilling and estuaries with minor reclamation were statistically distinct. ICOLLs are environmentally sensitive due to large catchment/estuary ratios and restricted access to the ocean. A full set of baseline data is provided to support future monitoring of anthropogenic impacts on the system.

PMID:34411956 | DOI:10.1016/j.marpolbul.2021.112851

J Inorg Biochem. 2021 Aug 8;224:111565. doi: 10.1016/j.jinorgbio.2021.111565. Online ahead of print.

ABSTRACT

Despite increasing use of silver nanoparticles (AgNPs) in different medicinal products, knowledge about their effects on hemostasis and platelets functionality is still scarce. Published scientific reports provide neither data on oxidative stress response of platelets to AgNPs nor information about the effects of AgNPs physicochemical properties on functionality and activation of platelets. This study aimed to explore the role of AgNPs surface functionalization on cell viability, particle uptake, oxidative stress response, and activation of platelets. Small sized, spherical AgNPs were surface functionalized by negatively charged sodium bis(2-ethylhexyl) sulphosuccinate (AOT), neutral polymer polyvinylpyrrolidone (PVP), positively charged polymer poly-l-lysine (PLL) and bovine serum albumin (BSA). Platelet viability, activation and particle uptake were evaluated by flow cytometry. Oxidative stress response was evaluated by measuring the levels of intracellular glutathione (GSH), peroxy and superoxide radicals using assays based on fluorescence dies. Cytotoxicity and uptake of AgNPs to platelets were found to be dose-dependent in a following order PLL-AgNP >> > BSA-AgNP > AOT-AgNP > PVP-AgNP. Particle internalization was further confirmed by transmission electron microscopy. Treatment of platelets with AgNPs induced superoxide radical formation, depletion of GSH and hyperpolarization of the mitochondrial membrane. Small, but statistically significant increase of P-selectin expression in cells treated with all AgNPs compared to non-treated controls evidenced AgNPs-induced activation of platelets. Increased PAC-1 expression was found only in platelets treated with PLL-AgNPs. Obtained results demonstrate that different surface decoration of AgNPs determines their biological effects on platelets highlighting the importance of careful design of AgNPs-based medicinal products regarding their biocompatibility and functionality.

PMID:34411938 | DOI:10.1016/j.jinorgbio.2021.111565

Forensic Sci Int. 2021 Jul 4;326:110897. doi: 10.1016/j.forsciint.2021.110897. Online ahead of print.

ABSTRACT

Diatoms are a useful form of environmental trace evidence, yielding a circumstantial link between persons and scenes of forensic interest. A developing empirical research base has sought to understand those factors affecting the transfer and persistence of freshwater diatoms on clothing and footwear surfaces. Although an initial study has demonstrated that diatoms can persist on clothing following weeks of wear, no previous research has explored the temporal dynamics of a persistent species assemblage over timescales pertinent to forensic investigations. This study therefore aimed to determine if: (1) valve morphology (size and shape) influences diatom persistence, (2) the relative abundance of taxa within an assemblage affects retention, and (3) a persistent diatom assemblage retrieved from clothing after one month can reliably be compared to the site of initial transfer. To build on previous research findings which highlighted the impact of substrate and environmental seasonality on diatom transfer and persistence, here, nine clothing materials were tested in spring before a seasonal comparison in the winter. Fabric swatches were immersed in a freshwater river, worn attached to clothing, and subsamples retrieved at regular intervals (hours, days, weeks) up to one month post-immersion. Diatoms were extracted using a H₂O₂ technique and analysed via microscopy. The results indicated that smaller diatoms (< 10 µm) are retained in significantly greater abundance, with no statistically significant difference between centric and pennate diatom loss over time. Although a persistent species assemblage was relatively stable over the one month of wear, significant differences were identified between clothing substrate in the spring and between the seasonal samples. The most abundant environmental taxa were consistently identified in the forensic samples, with greater variability attributed to the retention of relatively less common species. The findings suggest that, despite a loss in the abundance and species-richness of diatoms retrieved from clothing over time, a persistent assemblage may provide a useful circumstantial link to the site of initial transfer. The complex relationships between clothing type, environmental seasonality, and time since wear on retention, emphasise the need for diatom trace evidence to be carefully interpreted within an exclusionary framework, and the significance of any casework findings to be determined with reference to empirical evidence bases.

PMID:34411937 | DOI:10.1016/j.forsciint.2021.110897