A DWI-based hypoxia model shows robustness in an external prostatectomy cohort.

Introduction: Prostate cancer hypoxia is a negative prognostic biomarker. A promising MRI-based tool to assess hypoxia is the 'Consumption and Supply based Hypoxia' (CSH) model based on diffusion-weighted imaging (DWI). The aim of the study was to validate the association between the CSH hypoxia fraction (HFDWI) with pathological Grade Group (pGG) and pathological T-staging (pTstage) in an external prostatectomy cohort. Methods: Apparent diffusion coefficient (ADC) and fractional blood volume (fBV) maps were assessed from DWI data from 291 prostatectomies and combined by the CSH model. HFDWI was calculated for each lesion after median scaling of ADC and fBV to address differences in acquisition and analysis between centers. The absolute HFDWI values and the associations of HFDWI between pGG < 3 versus ≥ 3, and pTstage = 2 versus = 3 in the Netherlands Cancer Institute (NKI) cohort were compared to the obtained by original cohort (Oslo cohort). Statistical T- and Mann-Whitney tests (p<0.05) were performed. Pearson correlation was determined between HFDWI and individual pGG groups. Results: The HFDWI showed comparable absolute values and similar metric performance as in the original published cohort. Higher HFDWI values were observed for higher pGG (Oslo: 0.27; NKI: 0.24) compared to lower pGG (Oslo: 0.11; NKI: 0.17). Similar results were obtained for pTstage. Furthermore, HFDWI demonstrated a significant positive correlation with pGG groups 1-5 (ρ = 0.41, p<0.001). Conclusion: The CSH model exhibited sufficient robustness in the external cohort, suggesting a plausible reflection of true hypoxia and enabling the use of the HFDWI metric for further research into prostate cancer and hypoxia.

Efficient Magnon Injection and Detection via the Orbital Rashba-Edelstein Effect.

Orbital currents and accumulation provide a new avenue to boost spintronic effects in nanodevices. Here, we use interconversion effects between charge current and orbital angular momentum to demonstrate a dramatic increase in the magnon spin injection and detection efficiencies in nanodevices consisting of a magnetic insulator contacted by Pt/CuO_{x} electrodes. Moreover, we note distinct variations in efficiency for magnon spin injection and detection, indicating a disparity in the direct and inverse orbital Rashba-Edelstein effect efficiencies.

Review: Non-surgical artificial insemination and embryo recovery as safe tools for genetic preservation in small ruminants.

Artificial insemination (AI) and in vivo embryo production (or multiple ovulation and embryo transfer, MOET) programs are both instrumental in accelerating the propagation of genetically and economically superior goats and sheep. The aim of this review was to present the current gestalt of non-surgical AI and embryo recovery (NSER) procedures in small ruminants. Small body size, precluding rectal palpation, and highly limited penetrability of the uterine cervix in ewes are the major reasons for the scarce use of non-surgical assisted reproduction techniques in this species. As a result, AI and embryo recovery techniques in sheep mainly involve laparoscopy or laparotomy (LAP). In does, however, the Embrapa method of AI allows for successful intrauterine deposition of semen, resulting in pregnancy rates from 50 to 80% under field conditions (>3 000 goats inseminated) when frozen-thawed semen is used. After the administration of prostaglandin F2α (PGF2α), non-surgical (transcervical) embryo recovery is also feasible in goats, with the cervical penetration rate approaching 100%. There is a paucity of information on the efficacy of non-surgical AI using frozen semen in sheep, but the results are satisfactory with fresh, cooled, or chilled ram semen. An application of the NSER technique in ewes has greatly improved over the last decade, and cervical penetration rates of ∼90% can be achieved when a hormonal cervical dilation protocol using PGF2α, oxytocin, and/or estradiol ester (e.g., estradiol benzoate) is applied. In some genotypes of sheep, sufficient cervical dilation can be induced without estradiol ester included in the protocol. Several studies indicated that recovery of transferable quality ovine embryos using NSER is comparable to that employing a ventral midline laparotomy, and NSER is evidently a method of choice when animal welfare is concerned. Considering both the number of retrievable embryos and animal well-being, the NSER is a viable alternative for surgical procedures. With further developments, it has the makings of a primary, if not exclusive, embryo recovery technique in small ruminants worldwide.

Development and evaluations of the ancestry informative markers of the VISAGE Enhanced Tool for Appearance and Ancestry.

The VISAGE Enhanced Tool for Appearance and Ancestry (ET) has been designed to combine markers for the prediction of bio-geographical ancestry plus a range of externally visible characteristics into a single massively parallel sequencing (MPS) assay. We describe the development of the ancestry panel markers used in ET, and the enhanced analyses they provide compared to previous MPS-based forensic ancestry assays. As well as established autosomal single nucleotide polymorphisms (SNPs) that differentiate sub-Saharan African, European, East Asian, South Asian, Native American, and Oceanian populations, ET includes autosomal SNPs able to efficiently differentiate populations from Middle East regions. The ability of the ET autosomal ancestry SNPs to distinguish Middle East populations from other continentally defined population groups is such that characteristic patterns for this region can be discerned in genetic cluster analysis using STRUCTURE. Joint cluster membership estimates showing individual co-ancestry that signals North African or East African origins were detected, or cluster patterns were seen that indicate origins from central and Eastern regions of the Middle East. In addition to an augmented panel of autosomal SNPs, ET includes panels of 85 Y-SNPs, 16 X-SNPs and 21 autosomal Microhaplotypes. The Y- and X-SNPs provide a distinct method for obtaining extra detail about co-ancestry patterns identified in males with admixed backgrounds. This study used the 1000 Genomes admixed African and admixed American sample sets to fully explore these enhancements to the analysis of individual co-ancestry. Samples from urban and rural Brazil with contrasting distributions of African, European, and Native American co-ancestry were also studied to gauge the efficiency of combining Y- and X-SNP data for this purpose. The small panel of Microhaplotypes incorporated in ET were selected because they showed the highest levels of haplotype diversity amongst the seven population groups we sought to differentiate. Microhaplotype data was not formally combined with single-site SNP genotypes to analyse ancestry. However, the haplotype sequence reads obtained with ET from these loci creates an effective system for de-convoluting two-contributor mixed DNA. We made simple mixture experiments to demonstrate that when the contributors have different ancestries and the mixture ratios are imbalanced (i.e., not 1:1 mixtures) the ET Microhaplotype panel is an informative system to infer ancestry when this differs between the contributors.

Is the COVID-19 Pandemic Continuing to Impact Sexual and Reproductive Health Services for Adolescents? Findings From a 2021 Survey of US Physicians.

PURPOSE: We examined the impact of the COVID-19 pandemic in Fall 2021 on sexual and reproductive health (SRH) services among physicians whose practice provided these services to adolescents just before the pandemic. METHODS: Data were from the DocStyles online panel survey administered September-November 2021 to US physicians who reported their practice provided SRH services to adolescent patients before the pandemic (n = 948). We calculated prevalence of service delivery challenges (e.g., limited long-acting reversible contraception services) and use of strategies to support access (e.g., telehealth) in the month prior to survey completion, compared these estimates with prevalence "at any point during the COVID-19 pandemic", and examined differences by physician specialty and adolescent patient volume. RESULTS: Fewer physicians reported their practice experienced service delivery challenges in the month prior to survey completion than at any point during the pandemic. About 10% indicated limited long-acting reversible contraception and sexually transmitted infection testing services in the prior month overall; prevalence varied by physician specialty (e.g., 26% and 17%, respectively by service, among internists). Overall, about 25% of physicians reported reductions in walk-in hours, weekend/evening hours, and adolescents seeking care in the prior month. While most practices that initiated strategies supporting access to services during the pandemic used such strategies in the prior month, some practices (22%-37% depending on the strategy) did not. DISCUSSION: Findings suggest some physicians who serve adolescents continued to experience challenges providing SRH services in the Fall 2021, and some discontinued strategies to support access that had been initiated during the pandemic.

Can static hyperinflation predict exercise capacity in COPD?

INTRODUCTION: The diagnosis and severity assessment of COPD relies on spirometry, and in particular the FEV1. However, it has been proposed that hyperinflation and air-trapping are better predictors of exercise capacity and mortality than the FEV1. RESEARCH: QUESTION: Does static hyperinflation predict exercise capacity? METHODS: We conducted an observational prospective study. Patients with COPD referred to the lung function laboratory were consecutively recruited. Patients with hyperinflation (the experimental group) were compared to patients without hyperinflation (the control group). The sample sizes were determined assuming an effect size of 0.5 and a power of 0.80. RESULTS: We recruited 124 participants, of whom 87% were male, the mean age was 66.1 ± 8.8 years. 67% were symptomatic (GOLD B or D). Airflow limitation was moderate to severe in the majority of patients (median FEV1 47%, IQR 38-65%) and 43% of patients had static hyperinflation. The median 6MWD was 479 meters (404-510) and peak workload in CPET was 64 watts (46-88) with peak VO2 1.12 L/min, 0.89-1.31 L/min. Patients with lower FEV1, DLCO and IC/TLC and higher RV/TLC had reduced exercise capacity in both 6MWT and CPET, measured as lower distance, greater desaturation and ∆Borg dyspnoea, and reduced workload, peak VO2 and peak VE and higher desaturation and ventilatory limitation (VE/MVV). An IC/TLC < 0.33 predicted reduced exercise performance (peak O2 <60%). Dyspnoea assessed by mMRC and QoL measured by CAT and CCQ were also worse in the hyperinflation in COPD patients. CONCLUSION: In COPD patients, IC/TLC and RV/TLC are valuable predictors of exercise performance in both 6MWT and CPET and PRO.

Factors associated with the survival of primary maxillary anterior teeth after intrusive luxation: a retrospective longitudinal study.

PURPOSE: To evaluate the survival rate of primary maxillary anterior teeth following intrusive luxation and identify associated factors. METHODS: A retrospective longitudinal study was conducted at a primary dental trauma centre using 88 dental records of children with intrusive luxation between 2007 and 2018. The variables of interest were time the tooth remained in the alveolus, degree of intrusion, accentuated overjet, lip protection, visible plaque, compromised germ of the permanent successor, clinical signs of infectious and inflammatory processes, endodontic treatment, pulp canal obliteration, sex, age at the time of trauma, family income, mother's schooling, and immediate care. Descriptive, bivariate, and Cox regression analyses were performed (p < 0.05; 95% CI). RESULTS: The 88 dental records of children with intrusive luxation included 128 teeth. Survival rate throughout the follow-up period was 65.6% (n = 84). Age older than three years and eight months (HR 2.28; 95% CI 1.04-4.99; p = 0.039), the development of an infectious process (HR 3.51; 95% CI 1.39-8.86; p = 0.008), development of an inflammatory process (HR 2.35; 95% CI 1.17-4.71; p = 0.016) and compromised germ of the permanent successor (HR 4.38; 95% CI 1.99-9.61; p < 0.001) were associated with a lower survival rate of intruded primary maxillary anterior teeth. CONCLUSION: The survival rate during the follow-up period of intruded primary maxillary anterior teeth was considered high. A significantly lower survival rate was associated with age, the occurrence of an infectious process and inflammatory process, and the compromised germ of the permanent successor.

Occlusal Trauma Induces Neuroimmune Crosstalk for a Pain State.

Temporomandibular joint (TMJ) disorder caused by occlusal trauma is one of the most controversial topics in dentistry. Experimental traumatic occlusion (ETO) induced by metal crowns cemented to mandibular first molars in rats causes a long-lasting nociceptive response. This study aimed to elucidate whether ETO generates an increase in inflammatory mediators in the TMJ. In addition, the impact of ETO on trigeminal ganglia, neurotransmitter release, and satellite glial cell (SGC) activation was investigated. ELISA revealed enhanced inflammatory mediators, including TNF-α, IL-1ß, IL-6, CX3CL1, and ADAM-17 by Western blotting, in periarticular TMJ tissue after 28 d of ETO. In the trigeminal ganglia, ETO groups increased the release of the neurotransmitters substance P and glutamate. Overexpression of the AMPA receptor and upregulation of NMDA were observed in the 0.4- and 0.7-mm ETO groups, respectively, highlighting enhanced neuronal excitation. Increased IL-1ß and COX-2 mRNA levels in the 0.7-mm ETO group confirmed trigeminal ganglia SGC activation. Immunofluorescence and electrophoresis of SGC revealed increased pERK expression in the 0.7-mm ETO group. ERK phosphorylation was shown to be nociceptive specific, with its upregulation occurring in cases of chronic inflammatory pain. Increased PKA mRNA levels were observed in the 0.4-mm ETO group, while CREB mRNA levels were upregulated for both ETO groups. Electrophoresis showed overexpression of sodium channel Nav 1.7 in the 0.7-mm ETO group, while immunofluorescence revealed that Nav 1.7 is expressed in sensory trigeminal ganglia cells. The results of this study suggest that occlusal trauma induces neuroimmune crosstalk, with synthesis of proinflammatory/pronociceptive mediators, which increases neuronal activity in trigeminal ganglia via the activation of an inflammatory response cascade to develop a persistent neuroinflammatory state that leads to central sensitization.

Biological effects of the antihypertensive losartan under different ocean acidification scenarios.

Since the last decade, several studies have reported the presence and effects of pharmaceutical residues in the marine environment, especially those of the antihypertensive class, such as losartan. However, there is little knowledge about the physiological effects of losartan in marine invertebrates regarding its behavior under possible coastal ocean acidification scenarios. The objective of this study was to evaluate biological effects on marine organisms at different levels of the biological organization caused by the compound losartan in water and sediment under coastal ocean acidification scenarios. Water and sediment samples were collected at five sites around the Santos Submarine Sewage outfall (SSO) and two sites around the Guarujá Submarine Sewage Outfall (GSO). Losartan was found in concentrations ranging from

Impact of untreated dental caries and dental pain on sadness related to oral health of Brazilian children.

PURPOSE: Children should feel sad when they believe that a negative outcome is permanent. The sadness that an oral problem might bring tends to contribute to children's loneliness and increase the social stress levels. The aim of this study was to evaluate the impact of untreated dental caries, dental pain, malocclusion, and traumatic dental injury on prevalence of sadness related to oral health among Brazilian children. METHODS: This cross-sectional study was carried out with 397 children aged 8-10 years randomly selected from public and private schools in Diamantina, Brazil. The Brazilian version of the CPQ8-10 was applied. Sadness was collected through the question, "In the last month how often did you feel sad because of your teeth or mouth?" and dental pain through the question, "In the last month, how many times have you had pain in your teeth?" One calibrated examiner (Kappa value intra examiner: 0.77-0.91; Kappa value inter examiner: 0.80-1.00) performed the exam for dental caries (DMFT), malocclusion (DAI), and dental trauma (O'Brien). Parents answered questions addressing socioeconomic issues. Descriptive analyses, Chi-square test, and hierarchical Poisson regression models were performed (IC 95%; p < 0.05)." RESULTS: The prevalence of sadness related to oral health was 30.5% (n = 121). Sadness related to oral health was associated with untreated dental caries (PR: 1.46; 95% CI 1.32-2.46; p = 0.001 ) and dental pain (PR: 2.91; 95% CI 2.00-4.22; p < 0.001). Other clinical variables analyzed (traumatic dental injury and malocclusion) were not significantly associated with sadness related to oral health. CONCLUSIONS: Children with untreated dental caries and dental pain presented a higher report of sadness related to oral health.

Brachytherapy in paediatric craniopharyngiomas: a systematic review and meta-analysis of recent literature.

PURPOSES: Brachytherapy has been indicated as an alternative option for treating cystic craniopharyngiomas. Despite the difficulties regarding the complex nuclear infrastructure and consequent small number of brachytherapy studies, recent discoveries relating tumour characteristics to sensitivity to brachytherapy have stimulated this extensive systematic review and meta-analysis of the recent results aiming to summarise its efficacy and complications. METHODS: The systematic review was structured using PRISMA statements. The MEDLINE database was systematically reviewed from March 2010 to February 2021 to identify qualified trials dealing with radioisotope brachytherapy in cystic craniopharyngiomas in the paediatric population, emphasising tumour control rates and complications. RESULTS: A total of 228 individuals were analysed, of which 66 were children. The minimum average follow-up was 5 years. Considering the paediatric trials, partial and complete responses were achieved in 89% of patients with exclusively cystic lesions, compared to 58% in non-exclusively cystic lesions. The former observed progression in 3% of patients, while in the latter, 35% was reported. Visual and endocrine improvement reached 64% and 20%, respectively, in the first group, in contrast to 48% and 7% in the second group, respectively. There were similar results considering the non-exclusive paediatric series, but with less expressive numbers. CONCLUSION: These results reinforce the positive impact of radioisotope brachytherapy in the treatment of predominant monocystic or multicystic craniopharyngiomas, especially in the paediatric population, grounded by impressive tumour control rates, lower morbidities and single application in the majority of the cases. In the future, specific morphological tumour characteristics might be considered for a more assertive patient selection.

Familial hypercholesterolemia: Is there a role for PCSK9 and thrombin generation?

INTRODUCTION: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease. The prevalence of FH has previously been reported as 1 in 500 in the general population. This study aimed to evaluate the proprotein convertase subtilisin/kexin 9 (PCSK9) levels, lipid profile and thrombin generation in FH patients undergoing treatment or not. METHODS: Eighty individuals with FH were selected and distributed in 2 groups: individuals treated with statins alone or conjugate therapy (statin + ezetimibe) (T = 53) and those non treated (NT = 27). PCSK9 levels were determined by ELISA, the lipid profile by colorimetric enzyme method and thrombin generation assay (TGA) by CAT method. RESULTS: Individuals treated with conjugate therapy (statin + ezetimibe) showed a significant reduction in the levels of total cholesterol (TC) low density lipoprotein cholesterol (LDLc) and in the potential for thrombin generation (ETP with low and high concentration of tissue factor), compared to the treated individuals with monotherapy (statins). PCSK9 was positively correlated with increased levels of TC, LDLc and triglycerides, while TGA parameters were positively correlated with PCSK9 and lipid profile. CONCLUSION: PCSK9 levels appear to be associated with components of the lipid and hemostatic profiles, in addition to being influenced by age. In general, our findings suggest that combined therapy for the treatment of FH is associated with a significant improvement in both lipid and hemostatic profiles assessed by TGA, suggesting a reduction in atherogenic and thrombogenic risks and, therefore, more promising compared to the use of statin monotherapy.

Applicability of forensic facial approximation in the recognition process of unclaimed victims.

BACKGROUND: Identifying bodies in a state of putrefaction, skeletonization or mutilation is often difficult. In these cases, it is possible to use auxiliary methods such as forensic facial approximation, considering the possibility of recognition by a relative or acquaintance, helping to obtain ante-mortem data for the identification process. The aims of the present study were to evaluate the capacity of recognition of individuals from digital facial approximation and to verify the association between the level of understanding of the issue by evaluators and the recognition success index. METHODS: 16 skulls with previous photographic records were selected and then utilized for three-dimensional approximation using the digital technique, scanned by photogrammetry, and reconstructed by computerized method using open-source software. Twenty evaluators tried to recognize the facial approximation performed from images present in the photospreads. RESULTS: The mean overall score was 23.75%, and it was observed that in only five approximations (31.24%) the option of correct recognition of the victim was the one that obtained the highest number of selections. False positives and negatives corresponded, respectively, to 11.56% and 12.5%. CONCLUSIONS: It can be concluded that the methodology can provide recognition albeit in low numbers, and permitting the acquisition of ante-mortem data for the proper process of human identification through primary methods.

Neurocognitive evaluation using the International HIV Dementia Scale (IHDS) and Montreal Cognitive Assessment Test (MoCA) in an HIV-2 population.

OBJECTIVES: We aimed to characterize neurocognitive impairment (NI) in an HIV-2 population using an observational cross-sectional study in four Portuguese hospitals. METHODS: Adult HIV-2-infected patients were included. Montreal Cognitive Assessment Test (MoCA) and International HIV Dementia Scale (IHDS) scales were applied for screening of NI. Patient Health Questionnaire-9 (PHQ-9) and Instrumental Activities of Daily Living (IADL) scales were used for assessment of depression and functionality. A multivariate analysis was performed to assess for risk factors for NI. RESULTS: Eighty-one patients were included, 50.6% of African origin (n = 41) and 49.4% of Portuguese origin (n = 40). The MoCA scale showed alterations in 81.5% of patients (100% of migrants vs. 62.5% of non-migrants, P < 0.001) and the IHDS scale showed alterations in 42%. Both scales were altered simultaneously in 35.8%. Variables independently associated with NI were age [odds ratio (OR) = 0.885] and migrant status (OR = 9.150). CONCLUSIONS: Neurocognitive impairment (both scales altered) was present in 35.8%, which is comparable to what is described for HIV-1. The MoCA performed worse in the migrant population and might not be applicable in this setting.

Disaccharide anthocyanin delphinidin 3-O-sambubioside from Hibiscus sabdariffa L.: Candida antarctica lipase B-catalyzed fatty acid acylation and study of its color properties.

Enzymatic lipophilization is an important process to extend the use of anthocyanins in lipidic media. In this work delphinidin 3-O-sambubioside (Dp3sam) isolated from Hibiscus sabdariffa L. flower was esterified with octanoic acid using Candida antarctica lipase B. The physical-chemical properties of the new lipophilic pigment were studied by UV-vis spectroscopy. Dp3sam with chloride, acetate and formate as counter ions were employed to study the lipophilization reaction. The hydrolysis of the reagent was avoided with a formate counter ion and the expected product was achieved with a noteworthy change of solubility. 1D and 2D NMR characterization of Dp3sam-C8 confirmed that the lipophilization took place at the primary alcohol of the glucoside moiety. Overall, the Dp3sam-C8 ester presents a stabilization of the quinoidal base (blue color) at neutral or moderate alkaline pH, which foresees a potential use of this pigment as a broad kind of industries on lipo-soluble formulations.

Chemical and physical properties of nanocrystalline chitosan by the method: Modified nanochitosan complex and process of obtaining modified nanochitosan.

Nanocrystalline chitosan (NCC) is a modified form of chitosan, prepared from the method for obtaining chitosan acetate (CA). Due to the greater crystallinity of chitosan nanoparticles in relation to CA, NCC is more thermally stable and thus has great potential in the development of a new generation of biomaterials potentially useful in regenerative medicine and tissue engineering. NCC is also characterized by having similar properties to its precursor chitosan, such as its biocompatibility, bioactivity, ability to be bioabsorbed and lack of toxicity. One of the major problems associated with obtaining NCC is the low productivity of the methods. While known methods of obtaining nanostructures produce small amounts (milligrams), the method of synthesis for creating NCC from its salt is often more productive and less costly, and is patented by the authors of this work (registration number: BR10201702272). Thus, the objective of this study was to characterize NCC obtained through this innovative method, and analyze its chemical and physical properties using Fourier-Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC) and mechanical property analysis with the mean values for the elasticity module, the resistance to tensile strength and the tensile strength. The results indicate that this new process of obtaining the NCC did not modify the chemical structure of the chitosan. The structure of the film surface created was homogeneous and the mechanical properties emphasized the plastifying effect of glycerol under NCC. The thermogravimetric analysis of NCC indicated greater stability in the polysaccharide structure of the nanocrystalline, due to an increased crystalline region compared to the CA which was confirmed by DSC.

A thermodynamic view on the microsolvation of ions by rare gas: application to Li+ with argon.

We present a thermodynamic perspective of the microsolvation of ions by rare gas atoms, which is based on parallel tempering Monte Carlo (PTMC) simulations. This allows the establishment of a clear relationship between the structure of the solvation shells and the heat capacity (CV) as a function of the number of individual solvent species. The dependence of CV on the temperature allows the identification of the internal structure rearrangements and the onset of partial or total melting of the clusters. As an application, we have employed the PTMC technique to study the thermodynamic properties of clusters resulting from the microsolvation of Li+ by argon atoms. Specifically, calculations have been carried out for the clusters Li+Arn (n = 4-18, 33, 34, and 38) by applying two different potential energy surfaces (PESs): one includes only two-body interactions, while the other also incorporates three-body contributions. Whenever possible, we compare the present thermodynamic results with global optimization studies carried out previously (F. V. Prudente, J. M. C. Marques and F. B. Pereira, Phys. Chem. Chem. Phys., 2017, 19, 25707; W. S. Jesus et al., Int. J. Quantum Chem., 2019, 119, e25860). We conclude that the melting process arises for lower temperatures when the model PES accounts for three-body interactions. Additionally, we characterize the melting processes of the first and second solvation shells. For some specific clusters, structural rearrangements of the most external argon atoms are observed at very low temperatures.