Category: Nevin Manimala

Theriogenology. 2021 Sep 25;176:94-103. doi: 10.1016/j.theriogenology.2021.09.025. Online ahead of print.

ABSTRACT

Antifreeze proteins (AFPs) are synthesized by diverse non-mammalian species, allowing them to survive in severely cold environments. Since the 1990s, the scientific literature reports their use for low-temperature preservation of germplasm. The aim of this systematic review was to compile available scientific evidence regarding the use of AFP for low-temperature preservation of several reproductive specimens. Internet databases were consulted using the terms: “antifreeze protein” OR “AFP” OR “antifreeze glycoprotein” OR “AFGP” OR “ice-binding protein” OR “IBP” OR “thermal hysteresis protein” AND “cryopreservation”. From 56 articles, 87 experiments testing AFPs in low-temperature preservation of gametes, embryos or reproductive tissues/cells were fully analyzed and outcomes were annotated. A positive outcome was considered as a statistically significant improvement on any parameter evaluated after low-temperature preservation with AFP, whereas a negative outcome included worsening of any evaluated parameter, in comparison to untreated groups or groups treated with a lower concentration of AFP. The findings indicated that research on the use of AFP as a cryoprotectant for reproductive specimens has increased markedly over the past decade. Some experiments reported both positive and negative results, which depended, on AFP concentration in the preservation media. Variation in the outcomes associated with species was also observed. Among the 66 experiments conducted in mammals, 77.3% resulted in positive, and 28.8% in negative outcomes after the use of AFP. In fishes, positive and negative outcomes were observed in 71.4% and 33.3% of 21 experiments, respectively. Most positive outcomes included preserving cell post-warming survival. The beneficial effect of AFP supports its use in cryobiological approaches used in human and veterinary medicines and animal protein industry. Moreover, combination of different AFP types, or AFP with antioxidants, or even the use of AFP-biosimilar, comprise some promising approaches to be further explored in cryopreservation.

PMID:34600433 | DOI:10.1016/j.theriogenology.2021.09.025

Phys Med. 2021 Sep 29;90:108-114. doi: 10.1016/j.ejmp.2021.09.010. Online ahead of print.

ABSTRACT

PURPOSE: Dosiomics allows to parameterize regions of interest (ROIs) and to produce quantitative dose features encoding the spatial and statistical distribution of radiotherapy dose. The stability of dosiomics features extraction on dose cube pixel spacing variation has been investigated in this study.

MATERIAL AND METHODS: Based on 17 clinical delivered dose distributions (P_n), dataset has been generated considering all the possible combinations of four dose grid resolutions and two calculation algorithms. Each dose voxel cube has been post-processed considering 4 different dose cube pixel spacing values: 1x1x1, 2x2x2, 3x3x3 mm³ and the one equal to the planning CT. Dosiomics features extraction has been performed from four different ROIs. The stability of each extracted dosiomic feature has been analyzed in terms of coefficient of variation (CV) intraclass correlation coefficient (ICC).

RESULTS: The highest CV mean values were observed for PTV ROI and for the grey level size zone matrix features family. On the other hand, the lowest CV mean values have been found for RING ROI for the grey level co-occurrence matrix features family. P₃ showed the highest percentage of CV >1 (1.14%) followed by P₁₅ (0.41%), P₁ (0.29%) and P13 (0.19%). ICC analysis leads to identify features with an ICC >0.95 that could be considered stable to use in dosiomic studies when different dose cube pixel spacing are considered, especially the features in common among the seventeen plans.

CONCLUSION: Considering the observed variability, dosiomic studies should always provide a report not only on grid resolution and algorithm dose calculation, but also on dose cube pixel spacing.

PMID:34600351 | DOI:10.1016/j.ejmp.2021.09.010

Lung Cancer. 2021 Sep 20;161:163-170. doi: 10.1016/j.lungcan.2021.09.011. Online ahead of print.

ABSTRACT

OBJECTIVES: Programmed death-ligand 1 (PD-L1) expression is a predictive biomarker of response to immunotherapies targeting programmed death-1/PD-L1 in advanced-stage lung adenocarcinoma. The aim of this study was to investigate the associations between PD-L1 expression and clinicopathological features, prognosis, and driver oncogene alterations in patients with lung adenocarcinoma.

MATERIALS AND METHODS: We evaluated PD-L1 expression in 1,005 surgically resected lung adenocarcinoma specimens, by immunohistochemistry using the 22C3 antibody. PD-L1 positivity was defined based on the proportion of stained tumor cells (TPS) on tissue microarrays: <1% (negative), 1-49% (weakly positive), and ≥ 50% (strongly positive). Correlations between PD-L1 expression and clinicopathological features, prognosis, and driver oncogene (EGFR, KRAS, ALK, ROS1, and RET) alterations in lung adenocarcinoma were analyzed.

RESULTS: PD-L1 expression was negative in 726 (72%) of 1,005 tumors, weakly positive in 161 (16%), and strongly positive in 118 (12%). Male sex, smoking, elevated serum carcinoembryonic antigen levels, advanced pathological stages, high-grade tumors, predominantly solid tumors, tumors with lymphatic permeation or vascular or pleural invasion, tumors without EGFR mutations, and tumors with KRAS mutations were more common in patients with PD-L1-positive tumors (TPS ≥ 1%) than in those with PD-L1-negative tumors (TPS < 1%). PD-L1 positivity was not associated with ALK, ROS1, or RET fusion status. Although PD-L1 positivity was associated with poor overall survival and poor relapse-free survival in all patients, this was not statistically significant after adjusting for prognostic factors in the multivariate analysis. In the subgroup analysis according to driver oncogene alterations, PD-L1 positivity was associated with poor relapse-free survival only in patients with EGFR-mutated tumors.

CONCLUSION: Surgically resected lung adenocarcinomas with increased PD-L1 expression were biologically aggressive tumors that frequently occurred in male smokers. PD-L1 expression and its prognostic significance differed according to driver oncogene alterations.

PMID:34600407 | DOI:10.1016/j.lungcan.2021.09.011

Epilepsy Behav. 2021 Sep 29;124:108339. doi: 10.1016/j.yebeh.2021.108339. Online ahead of print.

ABSTRACT

INTRODUCTION: Idiopathic/genetic generalized epilepsy (GGE) accounts for 15-20% of all epilepsy cases. Neuropsychiatric comorbidities and disorders, such as attention-deficit hyperactivity disorder (ADHD), academic failure, and poor social competence, are present at a higher rate in patients with epilepsy compared with the general population. In this study, we aimed to determine the frequency of neuropsychiatric comorbidities in GGE subgroups, and to reveal the risk factors in the patient group with neuropsychiatric comorbidities.

MATERIAL AND METHOD: This hospital-based, cross-sectional study follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Patients with seizure-controlled GGE were invited to a semi-structured interview at the hospital. Variables [photosensitivity, valproic acid (VPA) resistance, timing of the neuropsychiatric comorbidities Attention deficit and hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and low academic performance), seizure control, and timing of the antiepileptic treatment] were statistically analyzed and evaluated in terms of their association with GGE subgroups [Generalized tonic-clonic seizures alone (EGTGS), juvenile myoclonic epilepsy (JME), and juvenile absence epilepsy (JAE)], RESULTS: Total 101 patients with GGE were included in the study and the mean age was 13.94 ± 1.66 years. A total of 12.9% (n = 13) of the patients had EGTGS, 49.5% (n = 50) had JME, and 37.6% (n = 38) had JAE. VPA resistance, photosensitivity, and the presence of neuropsychiatric symptoms before the starting of epilepsy were found to be risk factors in the GGE group with neuropsychiatric comorbidities compared with the group without neuropsychiatric comorbidities (p < 0.001). The subgroups of GGE did not show any relationship with psychiatric disorders, including ADHD, ODD, and low academic performance (neuropsychiatric comorbidities) (p > 0.005). No correlation was found between seizure control and decline in neuropsychiatric symptoms (p > 0.05).

CONCLUSION: In this study, the onset of psychiatric symptoms prior to the onset of epilepsy, photosensitivity, and VPA resistance were the most important factors affecting neuropsychiatric comorbidities. The JME, JAE, and EGTCS subgroups, early initiation of antiepileptic treatment, and seizure control were found to have no effect on poor psychosocial outcome and neuropsychiatric comorbidities.

PMID:34600282 | DOI:10.1016/j.yebeh.2021.108339

Arch Oral Biol. 2021 Sep 25;131:105272. doi: 10.1016/j.archoralbio.2021.105272. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to characterize Neolithic human maxillary molars from archeological remains at the Jiaojia site, Shandong, China, and compare their ultrastructural features with sex and age-matched modern locals.

DESIGN: Maxillary first (n = 86) and second (n = 80) molars in 5000-year-old individuals (n = 50) from the Jiaojia site were scanned by cone-beam computed tomography (CBCT). Sex and age-matched control groups were assigned from oral surgical patients at Shandong University. Images were analyzed for crown size, root length, root morphology, canal inter-orifice distances, mesiobuccal canal morphology, and second mesiobuccal (MB2) canal prevalence and location. Neolithic and modern values were compared statistically using Chi-squared and Mann-Whitney test at p < .05.

RESULTS: Crown and root size were smaller, and canal inter-orifice distances were shorter in Neolithic maxillary molars than their modern counterparts. For mesiobuccal roots, Weine’s Type I single canals were the most prevalent in Neolithic and modern first and second molars. MB2 canal prevalence were not significantly different (p > .05) in Neolithic (53.3%) or modern (60.5%) first molars, and Neolithic (11.3%) or modern (21.3%) second molars. But, MB2 prevalence was significantly higher for modern than ancient male first (p = .032) and second (p = .005) molars. Additionally, MB2 were located more mesially and closer to MB1 in Neolithic than modern molars.

CONCLUSIONS: Maxillary molar root and canal morphology of ancient 5000-year-old remains at the Jiaojia site resemble that of local patients. A trend towards larger tooth size, and more dispersed MB2 canals over this short evolutionary period warrants additional investigation.

PMID:34600333 | DOI:10.1016/j.archoralbio.2021.105272

Int J Food Microbiol. 2021 Sep 24;358:109421. doi: 10.1016/j.ijfoodmicro.2021.109421. Online ahead of print.

ABSTRACT

Although swine are less associated with STEC foodborne disease outbreaks, the potential for swine to serve as a source of STEC infections in human beings cannot be disregarded. This study compared eight USDA-approved antimicrobial intervention technologies to quantify their ability to reduce STEC contamination on market hog carcasses. Hogs were harvested to provide skin-on carcass sides, and eight sides (per three replications) were inoculated with a 7-strain STEC cocktail (ca. 5 log CFU/cm² across all external and body cavity surfaces). Each side was randomly assigned to a final pre-chill wash treatment administered in a commercial Chad carcass cabinet using a low-volume spray [3% lactic acid (lLA; 130 °F), 400 ppm peracetic acid (lPAA), or acidified 400 ppm peracetic acid (laPAA)] or a high-volume wash [ambient water (hAW), 400 ppm PAA (hPAA), 400 or 600 ppm hypobromous acid (hDBDMH), or 71 °C water (hHW)] treatment according to a randomized complete block study design. Post-treatment (after a 10-min hanging drip) and post-chilling (18 h at 2 °C) STEC reductions were compared for external skin-on surfaces and internal body cavity lean surface tissue. Post-treatment color changes were determined for lean, adipose, and skin carcass surfaces before and after chilling. When applied to the external, skin-on surface, the hHW, hPAA, and hDBDMH₆₀₀ deluge washes were significantly (P ≤ 0.05) more effective than the other intervention technologies, achieving STEC reductions of 3.8, 3.4, and 3.2 log CFU/cm², respectively. In comparison, the hAW control reduced STEC by 1.7-log CFU/cm² on the external, skin-on surface. The carcass interventions were less effective at reducing STEC populations attached to interior body cavity (diaphragm region), with post-chill populations reduced by 0.9-2.2 log cycles, while the hAW control wash achieved a 0.6-log reduction. None of the treatments negatively impacted instrumental carcass color. While all market hog carcass interventions reduced STEC populations, larger reductions were observed when applied to the external, skin-on surface, with the largest reductions achieved by the hHW, hPAA, and hDBDMH₆₀₀ deluge washes. These data equip pork processors with the information necessary to support decision-making when selecting an intervention technology.

PMID:34600270 | DOI:10.1016/j.ijfoodmicro.2021.109421

Child Abuse Negl. 2021 Sep 29;122:105344. doi: 10.1016/j.chiabu.2021.105344. Online ahead of print.

ABSTRACT

BACKGROUND: Child maltreatment is prevalent in the United States and carries long-term consequences. Parental substance use may have associations with child maltreatment. It is unclear whether co-occurring parental substance use aggravates childhood psychiatric outcomes related to suspected maltreatment.

OBJECTIVE: To compare psychiatric and healthcare utilization outcomes in children with suspected abuse reports, with and without documented parental substance use.

PARTICIPANTS AND SETTING: Retrospective cohort study (n = 2831) of children with suspected abuse/neglect (SANC) reports filed in the electronic health record between January 1, 2000 and January 1, 2016. Children who had SANC reports referencing parental substance use (n = 458) were compared with those who had SANC reports that did not reference substance use (n = 2346).

METHODS: Outcome data included ICD-10 coded medical and psychiatric diagnoses and healthcare utilization.

RESULTS: Compared to children who had a SANC report filed without parental substance use, children with parental substance use in a SANC showed significantly lower age-adjusted odds of anxiety disorder, mood disorder and externalizing disorder, and higher odds of a substance use disorder diagnosis. They were also less likely to present to an emergency department visit for any reason in the year prior to the report.

CONCLUSIONS: Children with exposure to parental substance use in a household where parental abuse or neglect was suspected had lower odds of adverse psychiatric outcomes as compared to children with suspected report of abuse or neglect unrelated to parental substance use. The present findings highlight the complex interplay of psychosocial factors associated with outcomes of childhood maltreatment.

PMID:34600277 | DOI:10.1016/j.chiabu.2021.105344

Drug Alcohol Depend. 2021 Sep 24;228:109074. doi: 10.1016/j.drugalcdep.2021.109074. Online ahead of print.

ABSTRACT

BACKGROUND: Cocaine use disorder (CUD) has significant consequences and there remain no FDA-approved pharmacotherapies. Ondansetron is an indirect dopaminergic modulator that has shown efficacy in alcohol use disorder, particularly in phenotypic and genotypic subgroups, and was found to be efficacious in a pilot dose-finding trial for CUD.

METHODS: One-hundred eight (108) adults with CUD were randomized to ondansetron 4 mg twice daily or placebo for 9 weeks and assessed up to thrice weekly to evaluate self-reported cocaine use and urine benzoylecgonine. Participants received cognitive-behavioral therapy and brief behavioral compliance enhancement therapy. Consenting participants (N = 79) provided blood samples for exploratory pharmacogenetic analyses.

RESULTS: Participants in both arms reduced cocaine use over time, but there was no statistically significant difference on percentage of cocaine-free days (PCFD; p = 0.972) or percentage of cocaine-free urine samples (PCFU; p = 0.909). Participants with early-onset CUD had greater improvement regardless of study arm (p = 0.002). Post hoc pharmacogenetic analyses demonstrated an interaction effect between treatment and rs1176713 SNP on PCFU in the total sample (p = 0.040) and African ancestry subset (p = 0.03). Constipation, fatigue, and somnolence were more common among ondansetron-treated participants (Fisher exact p < 0.05). Those who developed constipation were mostly rs1176713:GG carriers (Fisher exact p = 0.029).

CONCLUSIONS: Ondansetron did not demonstrate efficacy in the treatment of CUD. However, these preliminary results suggest a genotype-based variance in response to ondansetron in African ancestry individuals with CUD. Further studies are needed to validate findings for developing a personalized genomic approach for CUD treatment in racially and ethnically diverse populations.

PMID:34600264 | DOI:10.1016/j.drugalcdep.2021.109074

Drug Alcohol Depend. 2021 Sep 22;228:109086. doi: 10.1016/j.drugalcdep.2021.109086. Online ahead of print.

ABSTRACT

BACKGROUND: The United States’ 2019 outbreak of e-cigarette or vaping-associated lung injuries (EVALI) was linked to an additive most common in informally-sourced vaporizable marijuana concentrates. This study estimates how states’ recreational and medical marijuana policies related to their 2019 EVALI incidence and residents’ likelihood of vaping as their primary mode of marijuana use.

METHODS: Multivariable negative binomial regressions estimated associations between states’ total 2019 EVALI cases and marijuana policies: recreational legalization, medical legalization only, and whether medical-only policies allowed home cultivation, prohibited combustible use, or had operational dispensaries. Logistic regressions used survey data from the Behavioral Risk Factor Surveillance System’s 2016-2019 marijuana supplements to assess how these policies related to past-30-day marijuana users’ selection of vaping as their primary mode of use.

RESULTS: EVALI incidence was 42% lower in recreational marijuana states (95%CI=0.339,0.993), versus a positive but statistically insignificant association with medical legalization alone. Adjusting for policy attributes revealed heterogeneity: among medical-marijuana-only states, EVALI incidences were > 60% lower where laws allowed home cultivation (aIRR=0.374; 95%CI=0.196, 0.715). Similarly, among past-30-day marijuana users, odds of vaping as one’s primary mode of use were > 40% lower in medical-only states where home cultivation was allowed versus prohibited (aOR=0.588; 95%CI=0.365,0.946).

CONCLUSIONS: Marijuana policy attributes linked to lower EVALI incidences were also associated with reduced likelihoods of vaping as one’s primary mode of use. As additives in informally-sourced vaping concentrates could drive future EVALI cases, marijuana policy design should account for effects on mode of use in licit and illicit markets, to limit the scope of future outbreaks.

PMID:34600265 | DOI:10.1016/j.drugalcdep.2021.109086

Drug Alcohol Depend. 2021 Sep 23;228:109054. doi: 10.1016/j.drugalcdep.2021.109054. Online ahead of print.

ABSTRACT

BACKGROUND: Medication development research for cocaine use disorder (CUD) has been a longstanding goal in addiction research, but has not resulted in an FDA-approved treatment. Rising cocaine use rates underscore the need for efficient adaptive designs. This study compared differences between two doses of the selective serotonin reuptake inhibitor (SSRI) citalopram (versus placebo) on duration of cocaine abstinence and applied adaptive decision rules to select the ‘best efficacy’ dose.

METHODS: A double-blind, placebo-controlled, randomized Bayesian drop-the-loser (DTL) trial with three arms compared placebo to citalopram 20 mg and 40 mg. Adults (N = 107) with CUD attended thrice-weekly clinic visits for 9 weeks. The primary outcome was longest duration of abstinence (LDA), based on continuous cocaine-negative urine drug screens (UDS). The secondary outcome was probability of cocaine-negative UDS during treatment. A planned interim analysis performed at approximately 50% of recruitment dropped the least-effective active medication. Bayesian inference was used for all analyses with a pre-specified posterior probability (PP) threshold PP ≥ 95% considered statistically reliable evidence RESULTS: Citalopram 40 mg satisfied interim efficacy criteria and was retained for the second half of the trial. For LDA, analyses indicated PP = 82% and PP = 65% of benefit for 40 mg and 20 mg, respectively (each relative to placebo). The odds of having cocaine-negative UDS decreased in all groups over 9 weeks but remained higher for 40 mg (PP = 97.4%) CONCLUSIONS: Neither dose met the 95% PP threshold for the primary outcome; however, 40 mg provided moderate-to-strong evidence for positive effects on LDA and cocaine-negative UDS. The 40 mg dose was declared the “winner” in this DTL trial.

PMID:34600245 | DOI:10.1016/j.drugalcdep.2021.109054