Nevin Manimala

Proteins. 2022 Aug 14. doi: 10.1002/prot.26411. Online ahead of print.

ABSTRACT

The total free energy of a hydrated biomolecule and its corresponding decomposition of energy and entropy provides detailed information about regions of thermodynamic stability or instability. The free energies of four hydrated globular proteins with different net charges are calculated from a molecular dynamics simulation, with the energy coming from the system Hamiltonian and entropy using multiscale cell correlation. Water is found to be most stable around anionic residues, intermediate around cationic and polar residues, and least stable near hydrophobic residues, especially when more buried, with stability displaying moderate entropy-enthalpy compensation. Conversely, anionic residues in the proteins are energetically destabilised relative to singly solvated amino acids, while trends for other residues are less clear-cut. Almost all residues lose intra-residue entropy when in the protein, enthalpy changes are negative on average but may be positive or negative, and the resulting overall stability is moderate for some proteins and negligible for others. The free energy of water around single amino acids is found to closely match existing hydrophobicity scales. Regarding the effect of secondary structure, water is slightly more stable around loops, of intermediate stability around β strands and turns, and least stable around helices. An interesting asymmetry observed is that cationic residues stabilise a residue when bonded to its N-terminal side but destabilise it when on the C-terminal side, with a weaker reversed trend for anionic residues.

PMID:35964252 | DOI:10.1002/prot.26411

J Prosthodont. 2022 Aug 14. doi: 10.1111/jopr.13593. Online ahead of print.

ABSTRACT

PURPOSE: To determine the survival rate, incidence of prosthetic complications and patient satisfaction of implant fixed complete dental prostheses (IFCDPs) after a mean observation period of 1.4 years.

MATERIALS AND METHODS: Twenty-eight (28) eligible participants were recruited according to specific inclusion and exclusion criteria. The definitive metal-acrylic resin IFCDPs consisted of titanium bars veneered with acrylic resin and acrylic denture teeth. Prosthodontic complications, divided into major and minor, were monitored. Parameters such as gender, jaw location, bruxism, and occlusal scheme were evaluated. Moreover, a questionnaire was administered throughout the study to assess patient satisfaction. Poisson regression as well as repeated measures ANOVA were used for statistical analysis.

RESULTS: Fourteen (14) males and 14 females were enrolled and followed-up at 3, 6, and 12 months. All IFCDPs survived (100% survival rate). The most frequent minor complication was the loss of material used to close the screw access hole (20% out of total complications). The most frequent major complication was chipping of the acrylic denture teeth (77.14% out of total complications). Gender (P = 0.008) and bruxism (P = 0.030) were significant predictors for the total major complications (major wear and major chipping) while occlusal scheme was a significant predictor for major chipping events (P = 0.030).

CONCLUSIONS: While IFCDPs demonstrated high prosthetic survival rates, they also exhibited a high number of chipping events of the acrylic veneering material, especially in males, bruxers, and individuals with canine guidance occlusion. However, the occurrence of these prosthetic complications did not negatively affect patient satisfaction. This article is protected by copyright. All rights reserved.

PMID:35964246 | DOI:10.1111/jopr.13593

Asian Pac J Allergy Immunol. 2022 Aug 22. doi: 10.12932/AP-120821-1209. Online ahead of print.

ABSTRACT

BACKGROUND: Epinephrine 5 mg administered via the intranasal (IN) route was shown to be bioequivalent to epinephrine 0.3 mg administered via the intramuscular (IM) route in our preliminary study.

OBJECTIVE: To investigate the pharmacokinetics and pharmacodynamics of IN and IM epinephrine absorption in a larger group of healthy adults (n = 12).

METHODS: Each subject was administered IN saline, IN epinephrine (5 mg), and IM epinephrine (0.3 mg) on 3 separate days. Plasma epinephrine levels were determined using liquid chromatography-tandem mass spectrometry.

RESULTS: IN epinephrine administration showed significant systemic absorption compared to IN saline control with the areas under the curve (AUC0-180 min) of 4.4 (4.9) ± 4.0 and 0.2 (0.5) ± 0.3 ng.min/mL, respectively; the values are mean (median) ± standard deviation. IN epinephrine absorption was about 0.5-fold that of IM epinephrine (AUC0-180 min 10.0 (9.2) ± 8.6 ng.min/mL), but the difference was not statistically significant (p = 0.16). The mean peak epinephrine concentration and the time to reach it were also not significantly different between the IN and IM routes. The corresponding values were 120 pg/mL and 41 min for IN, and 209 pg/mL and 41 min for IM, respectively.

CONCLUSIONS: The systemic absorption of IN epinephrine 5 mg was significantly different from the control IN saline and about 0.5-fold that of IM epinephrine 0.3 mg. Although epinephrine administration via the less invasive IN route is safe and feasible, further investigations are necessary to achieve an adequate and consistent systemic absorption comparable to that of the conventional IM injection.

PMID:35964243 | DOI:10.12932/AP-120821-1209

Work. 2022 Aug 6. doi: 10.3233/WOR-220133. Online ahead of print.

ABSTRACT

BACKGROUND: Implications of entrepreneurial education (EE), entrepreneurial self-efficacy (ESE) and personality traits (PT) on the entrepreneurial intentions of the deaf is yet unknown in existing literature.

OBJECTIVE: To examine the influence of EE, ESE and PT on the entrepreneurial intentions among some 250 Deaf and Hard of hearing (DHH) students from two post-secondary institutions in Oyo state, Nigeria.

METHODS: A descriptive research design was adopted, while a structured paper questionnaire was used for data collection. The data generated were analysed using descriptive statistics and the inferential statistics of Pearson Product Moment Correlation and hierarchical multiple regression at a 0.05 level of significance.

RESULTS: The entrepreneurial intentions of DHH college students had a significant positive correlation with EE (r = 0.18, p < 0.05), agreeableness (r = 0.23, p < 0.05), and conscientiousness (r = 0.19, p < 0.05); but had a negative correlation with ESE, neuroticism and openness. Furthermore, personality traits and ESE were the highest predictors of entrepreneurial intention among DHH college students.

CONCLUSIONS: Personality traits were the greatest predictor of the entrepreneurial intention of DHH college students post the COVID-19 lockdowns in Nigeria. Therefore, higher education institutions should intensify their efforts in entrepreneurial education and parents of DHH students should encourage them to seek entrepreneurial opportunities.

PMID:35964226 | DOI:10.3233/WOR-220133

Technol Health Care. 2022 Aug 5. doi: 10.3233/THC-220190. Online ahead of print.

ABSTRACT

BACKGROUND: Human gait involves activities in nervous and musculoskeletal dynamics to modulate joint torques with time continuously for adapting to varieties of walking conditions.

OBJECTIVE: The goal of this paper is to estimate the joint torques of lower limbs in human gait based on Gaussian process.

METHOD: The potential uses of this study include optimization of exoskeleton assistance, control of the active prostheses, and modulating the joint torque for human-like robots. To achieve this, Gaussian process (GP) based data fusion algorithm is established with joint angles as the inputs.

RESULTS: The statistic nature of the proposed model can explore the correlations between joint angles and joint torques, and enable accurate joint-torque estimations. Experiments were conducted for 5 subjects at three walking speed (0.8 m/s, 1.2 m/s, 1.6 m/s).

CONCLUSION: The results show that it is possible to estimate the joint torques at different scenarios.

PMID:35964218 | DOI:10.3233/THC-220190

Restor Neurol Neurosci. 2022 Aug 6. doi: 10.3233/RNN-211237. Online ahead of print.

ABSTRACT

BACKGROUND: Traditional repetitive Transcranial Magnetic Stimulation (rTMS) remains applicable in speech studies on healthy participants. Although the procedure of inducing speech arrest by rTMS has been used for over 25 years, there are still significant discrepancies in its methodology.

OBJECTIVE: The study aimed to simplify and improve the old methodology of triggering speech arrest by (rTMS). Our goal was to establish the best step-by-step algorithm and verify the procedure on a representative group of participants.

METHODS: 47 healthy, right-handed volunteers (23 men and 24 women) at a median age of 23 (range 19-34) were included in the study. Handedness was determined using the Edinburgh Handedness Inventory Test. After setting the individual’s motor threshold (MT) and heuristic choice of the place of stimulation, which targeted Inferior Frontal Gyrus (IFG), participants were asked to count downwards from 20 to 10. While counting, a series of 2-second pulses was generated at a frequency of 2 Hz at 120% or 150% of MT. The procedure was video-recorded and subsequently assessed by 3 independent reviewers and self-assessed by participants on visual analogue scales for the effect and comfort of stimulation.

RESULTS: Speech arrest was induced in 45 people (95.7%). Language dominance was determined to be either left-sided (for 42.2%) or bilateral (55.3%). Total speech arrest was observed more often in participants for whom Broca’s area was active exclusively in the left hemisphere.

CONCLUSION: In our study, we present the step-by-step procedure for a simplified, as far as possible, methodology of inducing speech arrest using rTMS with its verification on a representative group of right-handed healthy individuals. Our results prove that the chosen stimulation parameters present a good efficacy ratio and seems to be justified. The traditional applications of rTMS in speech studies may be highly broadened if the methods used are further improved and simplified.

PMID:35964212 | DOI:10.3233/RNN-211237

Int J Risk Saf Med. 2022 Aug 10. doi: 10.3233/JRS-200087. Online ahead of print.

ABSTRACT

BACKGROUND: Gender dysphoria is characterised by a sense of distress because of discordance between the self-perception of gender identity and the assigned sex. Hormonal treatment of transgender males uses testosterone to induce and preserve masculinisation.

OBJECTIVE: The study investigated the safety of testosterone therapy in transgender males.

METHODS: The present study used a retrospective file review of transgender male subjects who were treated with testosterone (initially transdermal testosterone gel and subsequently parenteral testosterone undecanoate) for at least 18 months and had subsequently achieved a serum testosterone level within the normal range of cisgender male counterparts. Changes in somatometric data and blood biomarkers were investigated.

RESULTS: The mean testosterone serum levels after approximately 18 months of treatment were about 545 ng/dL (SD ± 94 ng/dL). There was a statistically significant rise in body mass index (𝜒d = +1.23 kg/m2) with a reduction in blood glucose (𝜒d = -5.33 mg/dL) as well as statistically significant increases in aspartate transaminase (𝜒d = +4.3 U/L), haemoglobin (𝜒d = +1.72 g/dL) and haematocrit (𝜒d = +4.76%). In contrast, there were no significant changes in the lipidaemic profile of the subjects.

CONCLUSIONS: Treatment with testosterone is routinely used for the promotion of virilising physical changes in transgender males. However, the likelihood of adverse effects of continuous administration treatment is still unclear. This study contributed to the notion that achieving testosterone levels within the target range is a prerequisite for the safety of the gender-affirming treatment.

PMID:35964205 | DOI:10.3233/JRS-200087

J Parkinsons Dis. 2022 Aug 12. doi: 10.3233/JPD-223295. Online ahead of print.

ABSTRACT

BACKGROUND: In advanced Parkinson’s disease (PD), dyskinesias and non-motor symptoms such as sleep dysfunction can significantly impair quality of life, and high-quality management is an unmet need.

OBJECTIVE: To analyze changes in dyskinesia and non-motor symptoms (including sleep) among studies with levodopa-carbidopa intestinal gel (LCIG) in patients with advanced PD.

METHODS: A comprehensive literature review identified relevant studies examining LCIG efficacy. Outcomes of interest were dyskinesia (UDysRS, UPDRS IV item 32), overall non-motor symptoms (NMSS), mentation/behavior/mood (UPDRS I), and sleep/daytime sleepiness (PDSS-2, ESS). The pooled mean (95% confidence interval) change from baseline per outcome was estimated for each 3-month interval with sufficient data (i.e., reported by≥3 studies) up to 24 months using a random-effects model.

RESULTS: Seventeen open-label studies evaluating 1,243 patients with advanced PD were included. All outcomes of interest with sufficient data for meta-analysis showed statistically significant improvement within 6 months of starting LCIG. There were statistically significant improvements in dyskinesia duration as measured by UPDRS IV item 32 at 6 months (-1.10 [-1.69, -0.51] h/day) and 12 months (-1.35 [-2.07, -0.62] h/day). There were statistically and clinically significant improvements in non-motor symptoms as measured by NMSS scores at 3 months (-28.71 [-40.26, -17.15] points). Significant reduction of NMSS burden was maintained through 24 months (-17.61 [-21.52, -13.70] points). UPDRS I scores significantly improved at 3 months (-0.39 [-0.55, -0.22] points). Clinically significant improvements in PDSS-2 and ESS scores were observed at 6 and 12 months in individual studies.

CONCLUSION: Patients with advanced PD receiving LCIG showed significant sustained improvements in the burden of dyskinesia and non-motor symptoms up to 24 months after initiation.

PMID:35964203 | DOI:10.3233/JPD-223295

J Huntingtons Dis. 2022 Aug 6. doi: 10.3233/JHD-220540. Online ahead of print.

ABSTRACT

BACKGROUND: Autonomy describes a psychological state of self-regulation of motivation and action, which is a central characteristic of healthy functioning. In neurodegenerative diseases measures of self-perception have been found to be affected by the disease. However, it has never been investigated whether measures of self-perception, like autonomy, is affected in Huntington’s disease.

OBJECTIVE: We investigated whether autonomy is affected in Huntington’s disease and if the degree of autonomy is associated with motor function, neuropsychiatric symptoms, cognitive impairments, and apathy.

METHODS: We included 44 premanifest and motor-manifest Huntington’s disease gene expansion carriers and 19 controls. Autonomy was examined using two self-report questionnaires, the Autonomy-Connectedness Scale-30 and the Index of Autonomous Functioning. All participants were examined according to motor function, cognitive impairments, and neuropsychiatric symptoms, including apathy.

RESULTS: Statistically significant differences were found between motor-manifest Huntington’s disease gene expansion carriers and premanifest Huntington’s disease gene expansion carriers or controls on two measures of autonomy. Between 25-38% of motor-manifest Huntington’s disease gene expansion carriers scored significantly below the normal level on subscales of autonomy as compared to controls. One autonomy subscale was associated with apathy (r = -0.65), but not with other symptoms of Huntington’s disease.

CONCLUSION: This study provides evidence for impaired autonomy in individuals with Huntington’s disease and an association between autonomy and apathy. The results underline the importance of maintaining patient autonomy and involvement in care throughout the disease.

PMID:35964199 | DOI:10.3233/JHD-220540

J Alzheimers Dis. 2022 Aug 11. doi: 10.3233/JAD-220649. Online ahead of print.

ABSTRACT

BACKGROUND: The relationship between serum uric acid (UA) and Alzheimer’s disease (AD) risk still remained ambiguous despite extensive attempts.

OBJECTIVE: Via the two-sample Mendelian randomization (MR) design, we aimed to examine the bidirectional causal relationships of serum UA, gout, and the risk of AD.

METHODS: Genetic variants of UA, gout, and AD were extracted from published genome-wide association summary statistics. The inverse-variance weighted (IVW, the primary method), and several sensitivity methods (MR-Egger, weighted median, and weighted mode) were used to calculate the effect estimates. Egger regression, MR-PRESSO and leave-one-SNP-out analysis were performed to identify potential violations.

RESULTS: Genetic proxies for serum UA concentration [odds ratio (ORIVW) = 1.09, 95% confidence interval (CI) = 1.01-1.19, p = 0.031] were related with an increased risk of AD using 25 single nucleotide polymorphisms (SNPs). This causal effect was confirmed by sensitivity analyses including MR-Egger (1.22, 1.06-1.42, p = 0.014), weighted median (1.18, 1.05-1.33, p = 0.006), and weighted mode (1.20, 1.07-1.35, p = 0.005) methods. No evidence of notable directional pleiotropy and heterogeneity were identified (p > 0.05). Three SNPs (rs2078267, rs2231142, and rs11722228) significantly drove the observed causal effects. Supportive causal effect of genetically determined gout on AD risk was demonstrated using two SNPs (ORIVW = 1.05, 95% CI = 1.00-1.11, p = 0.057). No reverse causal effects of AD on serum UA levels and gout risk were found.

CONCLUSION: The findings revealed a causal relationship between elevated serum UA level and AD risk. However, further research is still warranted to investigate whether serum UA could be a reliable biomarker and therapeutic target for AD.

PMID:35964198 | DOI:10.3233/JAD-220649