Category: Nevin Manimala

J Anim Sci. 2023 Feb 27:skad065. doi: 10.1093/jas/skad065. Online ahead of print.

ABSTRACT

Spray dried plasma (SDP) is commonly used in phase 1 diets for weanling pigs, but it is unknown if SDP affects energy or nutrient digestibility of the subsequent diet. Therefore, two experiments were conducted to test the null-hypothesis that inclusion of SDP in a phase 1 diet fed to weanling pigs will not affect energy or nutrient digestibility of a phase 2 diet without SDP. In Exp. 1, 16 newly weaned barrows with an initial body weight (BW) of 4.47 ± 0.35 kg were randomly allotted to a phase 1 diet without SDP or a diet including 6% SDP for 14 d. Both diets were fed on an ad libitum basis. All pigs (BW: 6.92 ± 0.42 kg) had a T-cannula surgically inserted in the distal ileum, moved to individual pens, and fed the common phase 2 diet for 10 d with ileal digesta collection on d 9 and 10. In Exp. 2, 24 newly weaned barrows (initial BW: 6.60 ± 0.22 kg) were randomly allotted to phase 1 diets without SDP or a diet containing 6% SDP for 20 d. Both diets were provided on an ad libitum basis. All pigs (BW: 9.37 ± 1.40 kg) were then moved to individual metabolism crates and fed the common phase 2 diet for 14 d with the initial 5 d being the adaptation period to the diet followed by 7 d of fecal and urine collection according to the marker-to-marker procedure. The apparent ileal digestibility (AID) of starch, crude protein (CP), amino acids (AA), and acid hydrolyzed ether extract (AEE), was determined in Exp. 1, and the apparent total tract digestibility (ATTD) of gross energy (GE), insoluble-, soluble-, and total-dietary fiber, Ca, and P, and the retention and biological value of N were determined in Exp. 2. The statistical model included diet as fixed effect and block and pig within block as random effects. Results of Exp. 1 indicated that the AID of starch, CP, AEE, and AA in phase 2 were not affected by phase 1 treatment. Results of Exp. 2 indicated that the ATTD of GE, insoluble-, soluble-, and total-dietary fiber, Ca, and P and N retention and biological value in phase 2 were also not affected by phase 1 treatment. In conclusion, feeding weanling pigs a diet with 6% SDP in phase 1 did not affect the AID or ATTD of energy and nutrients in a phase 2 diet without SDP.

PMID:36848328 | DOI:10.1093/jas/skad065

Horm Mol Biol Clin Investig. 2023 Feb 27. doi: 10.1515/hmbci-2022-0042. Online ahead of print.

ABSTRACT

Major Depressive Disorder (MDD) is a mood disorder classified as a persistent depressive mood and loss of interest lasting for more than two weeks and accompanied by a list of symptoms outlined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) diagnostic criteria. MDD affects approximately 264 million people worldwide and is the most prevailing form of neuropsychiatric disorder. Owing to the probable hypothesized pathophysiology of MDD being an outcome of abnormalities in the amino acid neurotransmitter system, including glutamate (the primary excitatory neurotransmitter) and γ-aminobutyric acid (GABA), SAGE-217 (Zuranolone) is being evaluated as a possible therapeutic treatment for MDD. Zuranolone is a synthetic, neuroactive steroid (NAS) and positive allosteric modulator (PMA) of GABAA receptors, regulating both synaptic and extra-synaptic release of GABA. It is administered as a once-daily oral dose for 2 weeks due to its low-moderate clearance. A change in total HAM-D score from baseline was the primary end-point of all the trials. A phase II trial conducted to evaluate the efficacy and safety of Zuranolone (30 mg, once-daily dose), described a significant reduction in total HAM-D score at day 14 and reported the drug to be well tolerated with headache, dizziness, nausea, and somnolence as the most common adverse events (AE). Additional phase III trials were also conducted to evaluate similar outcomes, the interim topline results of which have been released. Consequently, this article attempts to briefly analyze the pharmacology of Zuranolone, review the available clinical data and outcomes regarding its use, and evaluate its place as a prospective novel therapy in the effective management of MDD.

PMID:36848317 | DOI:10.1515/hmbci-2022-0042

Stat Atlases Comput Models Heart. 2022;13593:258-268. doi: 10.1007/978-3-031-23443-9_24.

ABSTRACT

Hypoplastic left heart syndrome (HLHS) is a congenital heart disease characterized by incomplete development of the left heart. Children with HLHS undergo a series of operations which result in the tricuspid valve (TV) becoming the only functional atrioventricular valve. Many HLHS patients develop tricuspid regurgitation and right ventricle enlargement which is associated with heart failure and death without surgical intervention on the valve. Understanding the connections between the geometry of the TV and its function remains extremely challenging and hinders TV repair planning. Traditional analysis methods rely on simple anatomical measures which do not capture information about valve geometry in detail. Recently, surface-based shape representations such as SPHARM-PDM have been shown to be useful for tasks such as discriminating between valves with normal or poor function. In this work we propose to use skeletal representations (s-reps), a more feature-rich geometric representation, for modeling the leaflets of the tricuspid valve. We propose an extension to previous s-rep fitting approaches to incorporate application-specific anatomical landmarks and population information to improve correspondence. We use several traditional statistical shape analysis techniques to evaluate the efficiency of this representation: using principal component analysis (PCA) we observe that it takes fewer modes of variation compared to boundary-based approaches to represent 90% of the population variation, while distance-weighted discrimination (DWD) shows that s-reps provide for more significant classification between valves with less regurgitation and those with more. These results show the power of using s-reps for modeling the relationship between structure and function of the tricuspid valve.

PMID:36848309 | PMC:PMC9949511 | DOI:10.1007/978-3-031-23443-9_24

J Feline Med Surg. 2023 Feb;25(2):1098612X231154463. doi: 10.1177/1098612X231154463.

ABSTRACT

OBJECTIVES: This randomised, prospective, masked clinical trial evaluated the postoperative analgesic efficacy of an ultrasound-guided transversus abdominis plane block (TAPB) with bupivacaine in cats undergoing ovariohysterectomy.

METHODS: Thirty-two healthy adult female cats undergoing elective ovariohysterectomy were randomised to undergo TAPB with bupivacaine (treatment group [TG], n = 16) vs placebo (control group [CG], n = 16) in addition to preoperative analgesia with buprenorphine (0.02 mg/kg IM). All patients received a general anaesthetic and, before surgical incision, a bilateral two-point (subcostal and lateral-longitudinal) TAPB was performed using 1 ml/kg bupivacaine 0.25% (0.25 ml/kg/point) or saline. Each cat was assessed by a blinded investigator before premedication (0 h) and at 1, 2, 3, 4, 8, 10 and 24 h postoperatively using the UNESP-Botucatu Feline Pain Scale – short form. Buprenorphine (0.02 mg/kg IV) and meloxicam (0.2 mg/kg SC) were administered when pain scores were ⩾4/12. Ten hours postoperatively, meloxicam was administered to cats that did not receive rescue analgesia. Statistical analysis included Student’s t-tests, Wilcoxon tests and χ² tests, and a linear mixed model with Bonferroni corrections (P <0.05).

RESULTS: Of the 32 cats enrolled, three in the CG were excluded from the analysis. The prevalence of rescue analgesia was significantly higher in the CG (n = 13/13) than in the TG (n = 3/16; P <0.001). Only one cat in the CG required rescue analgesia twice. Pain scores were significantly higher in the CG compared with the TG at 2, 4 and 8 h postoperatively. Mean ± SD pain scores were significantly higher in the CG, but not in the TG, at 2 (2.1 ± 1.9), 3 (1.9 ± 1.6), 4 (3.0 ± 1.4) and 8 h postoperatively (4.7 ± 0.6) than at 0 h (0.1 ± 0.3).

CONCLUSIONS AND RELEVANCE: A bilateral ultrasound-guided two-point TAPB with bupivacaine in combination with systemic buprenorphine provided superior postoperative analgesia than buprenorphine alone in cats undergoing ovariohysterectomy.

PMID:36848291 | DOI:10.1177/1098612X231154463

Eur J Obstet Gynecol Reprod Biol X. 2023 Feb 8;17:100180. doi: 10.1016/j.eurox.2023.100180. eCollection 2023 Mar.

ABSTRACT

OBJECTIVE: Characterize the risk for adverse pregnancy, delivery and neonatal outcomes among different advanced maternal ages (AMA).

STUDY DESIGN: We conducted a population-based retrospective cohort study using data from the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample to characterize adverse pregnancy, delivery and neonatal outcomes among different AMA groups. Patients aged 44-45 (n = 19,476), 46-49 (n = 7528) and 50-54 years (n = 1100) were compared to patients aged 38-43 years (n = 499,655). A multivariate logistic regression analysis adjusted for statistically significant confounding variables.

RESULTS: With advancing age, rates of chronic hypertension, pregestational diabetes, thyroid disease and multiple gestation increased (p < 0.001). The adjusted risk of hysterectomy and need for blood transfusion substantially increased with advancing age, reaching up to an almost 5-fold (aOR, 4.75, 95 % CI, 2.76-8.19, p < 0.001) and 3-fold (aOR, 3.06, 95 % CI, 2.31-4.05, p < 0.001) increased risk, respectively, in patients aged 50-54 years. The adjusted risk of maternal death increased 4-fold in patients aged 46-49 years (aOR, 4.03, 95 % CI, 1.23-13.17, p = 0.021). Adjusted risks of pregnancy-related hypertensive disorders, including gestational hypertension and preeclampsia, increased by 28-93 % across advancing age groups (p < 0.001). Adjusted neonatal outcomes demonstrated up to a 40 % elevated risk of intrauterine fetal demise in patients aged 46-49 years (aOR, 1.40, 95 % CI, 1.02-1.92, p = 0.04) and a 17 % increased risk of having a small for gestational age neonate in patients aged 44-45 years (aOR, 1.17, 95 % CI, 1.05-1.31, p = 0.004).

CONCLUSIONS: Pregnancies at AMA are at increased risk for adverse outcomes, particularly for pregnancy-related hypertensive disorders, hysterectomy, blood transfusion, and maternal and fetal mortality. Although comorbidities associated with AMA influence the risk of complications, AMA was demonstrated to be an independent risk factor for major complications, with its impact varying across ages. This data imparts clinicians with the ability to provide more specific counseling to patients of varied AMA. Older patients seeking to conceive must be counseled regarding these risks in order to make well-informed decisions.

PMID:36846599 | PMC:PMC9945696 | DOI:10.1016/j.eurox.2023.100180

Front Mol Neurosci. 2023 Feb 9;16:1092864. doi: 10.3389/fnmol.2023.1092864. eCollection 2023.

ABSTRACT

One of the most important yet still underappreciated mechanisms of depression is distorted cognition, with aberrant sensitivity to negative feedback being one of the best-described examples. As serotonin has been identified as an important modulator of sensitivity to feedback and because the hippocampus has been implicated in the mediation of learning from positive and negative outcomes, the present study aimed to identify differences in the expression of various genes encoding 5-HT receptors in this brain region between the rats displaying trait sensitivity and insensitivity to negative feedback. The results demonstrated that trait sensitivity to negative feedback is associated with increased mRNA expression of the 5-HT2A receptors in the rat ventral hippocampus (vHipp). Further analysis revealed that this increased expression might be modulated epigenetically by miRNAs with a high target score for the Htr2a gene (miR-16-5p and miR-15b-5p). Additionally, although not confirmed at the protein level, trait sensitivity to negative feedback was associated with decreased expression of mRNA encoding the 5-HT7 receptor in the dorsal hippocampus (dHipp). We observed no statistically significant intertrait differences in the expression of the Htr1a, Htr2c, and Htr7 genes in the vHipp and no statistically significant intertrait differences in the expression of the Htr1a, Htr2a, and Htr2c genes in the dHipp of the tested animals. These results suggest that resilience to depression manifested by reduced sensitivity to negative feedback may be mediated via these receptors.

PMID:36846570 | PMC:PMC9948091 | DOI:10.3389/fnmol.2023.1092864

Dermatol Res Pract. 2023 Feb 15;2023:4592087. doi: 10.1155/2023/4592087. eCollection 2023.

ABSTRACT

Health care spending in Italy is high and continues to increase; assessing the long-term health and economic outcomes of new therapies is essential. Atopic dermatitis (AD) is a chronic, pruritic, immune-mediated inflammatory dermatosis, a clinical condition that significantly affects patients’ quality of life at a high cost and requires continuous care. This retrospective study aimed to assess the direct cost and adverse drug reactions (ADRs) of Dupilumab and patients’ clinical outcomes. All AD patients treated with Dupilumab at the Sassari University Hospital, Italy, between January 2019 and December 2021 were included. Eczema Area Severity Index, Dermatology Life Quality Index, and Itch Numeric Rating Scale scores were measured. ADRs and drug expenses were analyzed. A statistically significant posttreatment improvement was observed for all the indices measured: EASI (P < 0.0001), DLQI (P < 0.0001), NRS (P < 0.0001). The total expenditure for Dupilumab, in the observed period, amounted to € 589.748,66 for 1358 doses, and a positive correlation was shown between annual expenditure and delta percentage of variation pre- and posttreatment for the clinical parameters evaluated.

PMID:36846564 | PMC:PMC9946764 | DOI:10.1155/2023/4592087

Int J Clin Trials. 2022 Apr-Jun;9(2):107-117. doi: 10.18203/2349-3259.ijct20221110. Epub 2022 Apr 25.

ABSTRACT

BACKGROUND: To exchange the type of subjective Bayesian prior selection for assumptions more directly related to statistical decision making in clinician studies and trials, the decreasingly informative prior (DIP) is considered. We expand standard Bayesian early termination methods in one-parameter statistical models for Phase II clinical trials to include decreasingly informative priors (DIP). These priors are designed to reduce the chance of erroneously adapting trials too early by parameterize skepticism in an amount always equal to the unobserved sample size.

METHOD: We show how to parameterize these priors based on effective prior sample size and provide examples for common single-parameter models, include Bernoulli, Poisson, and Gaussian distributions. We use a simulation study to search through possible values of total sample sizes and termination thresholds to find the smallest total sample size (N) under admissible designs, which we define as having at least 80% power and no greater than 5% type I error rate.

RESULTS: For Bernoulli, Poisson, and Gaussian distributions, the DIP approach requires fewer patients when admissible designs are achieved. In situations where type I error or power are not admissible, the DIP approach yields similar power and better-controlled type I error with comparable or fewer patients than other Bayesian priors by Thall and Simon.

CONCLUSIONS: The DIP helps control type I error rates with comparable or fewer patients, especially for those instances when increased type I error rates arise from erroneous termination early in a trial.

PMID:36846554 | PMC:PMC9957559 | DOI:10.18203/2349-3259.ijct20221110

Adv Neurol (Singap). 2023 Mar 31;2(1):247. doi: 10.36922/an.247. Epub 2023 Feb 3.

ABSTRACT

BACKGROUND: Traumatic brain injuries (TBIs) are associated with high mortality and morbidity. Depressed skull fractures (DSFs) are a subset of fractures characterized by either direct or indirect brain damage, compressing brain tissue. Recent advances in implant use during primary reconstruction surgeries have shown to be effective. In this systematic review, we assess differences in titanium mesh, polyetheretherketone (PEEK) implants, autologous pericranial grafts, and methyl methacrylate (PMMA) implants for DSF treatment.

METHODS: A literature search was conducted in PubMed, Scopus, and Web of Science from their inception to September 2022 to retrieve articles regarding the use of various implant materials for depressed skull fractures. Inclusion criteria included studies specifically describing implant type/material within treatment of depressed skull fractures, particularly during duraplasty. Exclusion criteria were studies reporting only non-primary data, those insufficiently disaggregated to extract implant type, those describing treatment of pathologies other than depressed skull fractures, and non-English or cadaveric studies. The Newcastle-Ottawa Scale was utilized to assess for presence of bias in included studies.

RESULTS: Following final study selection, 18 articles were included for quantitative and qualitative analysis. Of the 177 patients (152 males), mean age was 30.8 years with 82% implanted with autologous graft material, and 18% with non-autologous material. Data were pooled and analyzed with respect to the total patient set, and additionally stratified into those treated through autologous and non-autologous implant material.There were no differences between the two cohorts regarding mean time to encounter, pre-operative Glasgow coma scale (GCS), fracture location, length to cranioplasty, and complication rate. There were statistically significant differences in post-operative GCS (p < 0.0001), LOS (p = 0.0274), and minimum follow-up time (p = 0.000796).

CONCLUSION: Differences in measurable post-operative outcomes between implant groups were largely minimal or none. Future research should aim to probe these basic results deeper with a larger, non-biased sample.

PMID:36846546 | PMC:PMC9948107 | DOI:10.36922/an.247

Transportation (Amst). 2023 Feb 21:1-35. doi: 10.1007/s11116-023-10371-7. Online ahead of print.

ABSTRACT

Determining bike-sharing usage patterns and their explanatory factors on demand is essential for the effective and efficient operation of bike-sharing systems (BSSs). Most BSSs provide different passes that vary with the period of use. However, studies investigating the differences in usage patterns are rare compared to studies conducted at the system level, even though explanatory factors depending on the type of pass may cause different characteristics in terms of usage patterns. This study explores the differences in the usage patterns of BSSs and the impact of explanatory factors on the demand depending on the type of pass. Various machine learning techniques, including clustering, regression, and classification, are used, in addition to basic statistical analysis. As observed, long-term season passes of over six months are mainly used for transportation (especially commuting), whereas one-day or short-term season passes seem to be used more for leisure than for other purposes. Furthermore, differences in the purpose of bike rentals seem to cause differences in usage patterns and variations in demand over time and space. This study improves ther understanding of the usage patterns that appear differently for each pass type, and provides insights into the efficient operation of BSSs in urban areas.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11116-023-10371-7.

PMID:36846545 | PMC:PMC9942648 | DOI:10.1007/s11116-023-10371-7