Molecular Characterization of Echinococcus canadensis (Cestoda, Taeniidae) in Wolf from the Kirov Region.

This work presents the results of studying the molecular characteristics of parasitic tapeworms Echinococcus canadensis. The helminths were discovered during the autopsy of a wolf (Canis lupus Linnaeus, 1758) killed by hunters in the Kirov oblast in 2021. A molecular phylogenetic study was performed by analyzing the sequence of a fragment of the first subunit of the mitochondrial cytochrome oxidase gene (CoxI). It was found that the detected echinococci belong to the G10 genotype of E. canadensis, which is common in wolves in the northern territories of the Holarctic. We discovered four positions at which the substitutions characteristic only of this genotype are revealed. A substitution at one of the positions that is characteristic exclusively for the representatives of the G10 genotype found in Russia and Finland was also discovered.

Computational prediction of crucial genes involved in gonorrhea infection and neoplastic cell transformation: A multiomics approach.

Neisseria gonorrheae, the causative agent of genitourinary infections, has been associated with asymptomatic or recurrent infections and has the potential to form biofilms and induce inflammation and cell transformation. Herein, we aimed to use computational analysis to predict novel associations between chronic inflammation caused by gonorrhea infection and neoplastic transformation. Prioritization and gene enrichment strategies based on virulence and resistance genes utilizing essential genes from the DEG and PANTHER databases, respectively, were performed. Using the STRING database, protein‒protein interaction networks were constructed with 55 nodes of bacterial proteins and 72 nodes of proteins involved in the host immune response. MCODE and cytoHubba were used to identify 12 bacterial hub proteins (murA, murB, murC, murD, murE, purN, purL, thyA, uvrB, kdsB, lpxC, and ftsH) and 19 human hub proteins, of which TNF, STAT3 and AKT1 had high significance. The PPI networks are based on the connectivity degree (K), betweenness centrality (BC), and closeness centrality (CC) values. Hub genes are vital for cell survival and growth, and their significance as potential drug targets is discussed. This computational study provides a comprehensive understanding of inflammation and carcinogenesis pathways that are activated during gonorrhea infection.

Acceptability of levofloxacin dispersible and non-dispersible tablet formulations in children receiving TB preventive treatment.

BACKGROUND: We evaluated the palatability and acceptability of a 100 mg dispersible and a non-dispersible 250 mg levofloxacin (LVX) tablet formulation in children. METHODS: Perform was a randomised, open-label, cross-over trial of the relative bioavailability of LVX dispersible vs. crushed non-dispersible tablets in children aged <6 years routinely receiving TB preventive treatment. Children and caregivers completed Likert- and ranking-type measures on the acceptability of both formulations. We used summary, comparative and ranking statistics to characterise formulation acceptability. RESULTS: A total of 25 children were enrolled (median age: 2.6 years, IQR 1.6-4.0). Caregivers reported frequent challenges with preventive therapy in routine care prior to study entry, including taste of tablets (n = 14, 56%), vomiting/spitting out medicines (n = 11, 44%), and children refusing medicines (n = 10, 40%). Caregivers reported that the dispersible formulation was easier for their child to take than the non-dispersible formulation (P = 0.0253). Mean ranks for caregiver's formulation preferences (dispersible tablets: 1.48, SD ±0.71; non-dispersible tablets: 2.12, SD ±0.67; routinely available formulations: 2.40 SD ±0.82) differed significantly (Friedman's F 11.120; P < 0.0038); post-hoc testing showed dispersible tablets were preferred over non-dispersible (P = 0.018) and routinely available LVX formulations (P < 0.001). CONCLUSIONS: The dispersible LVX 100 mg tablet formulation was preferred and should be prioritised for integration into routine care.

CONTEXTE: Nous avons évalué la palatabilité et l'acceptabilité d'un comprimé dispersible de 100 mg et d'un comprimé non dispersible de 250 mg de lévofloxacine (LVX) chez les enfants. MÉTHODES: Perform était un essai randomisé, ouvert et croisé de la biodisponibilité relative des comprimés dispersibles LVX par rapport aux comprimés non dispersibles écrasés chez des enfants âgés de moins de 6 ans recevant régulièrement un traitement préventif contre la TB. Les enfants et les soignants ont rempli des questionnaires de type Likert et de classement sur la tolérance des deux formulations. Nous avons utilisé des statistiques sommaires, comparatives et de classement pour caractériser la tolérance à la formulation. RÉSULTATS: Au total, 25 enfants ont été recrutés (âge médian : 2,6 ans ; IQR 1,6­4,0). Les soignants ont signalé des problèmes fréquents liés au traitement préventif dans le cadre des soins de routine avant le début de l'étude, notamment le goût des comprimés (n = 14, 56%), le fait de vomir ou de recracher les médicaments (n = 11, 44%) et le fait que les enfants refusent les médicaments (n = 10, 40%). Les soignants ont déclaré que la formulation dispersible était plus facile à prendre pour leur enfant que la formulation non dispersible (P = 0,0253). Les classements moyens pour les préférences de formulation des soignants (comprimés dispersibles : 1,48 ; SD ±0,71 ; comprimés non dispersibles : 2,12 ; SD ±0,67 ; formulations couramment disponibles : 2,40 ; SD ±0,82) différaient de manière significative (Friedman's F 11,120 ; P < 0,0038) ; les tests post-hoc ont montré que les comprimés dispersibles étaient préférés aux comprimés non dispersibles (P = 0,018) et aux formulations LVX couramment disponibles (P < 0,001). CONCLUSION: La formulation dispersible des comprimés de LVX 100 mg a été préférée et devrait être intégrée en priorité dans les soins de routine.

Modern multiligament knee injury surgical reconstruction techniques can achieve excellent knee function and patient satisfaction, with low complication rates.

PURPOSE: To report on the recovery of strength and functional capacity symmetry following multiligament knee surgical reconstruction (MLKR), as well as the capacity of athletes to return to sport. METHODS: This prospective cohort study recruited 47 patients undergoing MLKR between February 2018 and July 2021. Forty patients had full outcome assessment postoperatively at 6, 12 and 24 months and were included in the analysis, 75% were knee dislocation one injuries and 60% were injured playing sport. Patient-reported outcome measures (PROMs) assessed included the International Knee Documentation Committee score, the Knee Outcome Survey, the Lysholm Knee Score and the Tegner Activity Scale (TAS). Patient satisfaction was also assessed. Objective assessment included assessment of active knee flexion and extension range of motion (ROM), the single (single horizontal hop for distance [SHD]) and triple (triple horizontal hop for distance [THD]) hop tests for distance and peak isokinetic knee flexor/extensor torque. RESULTS: All PROMs significantly improved (p < 0.001) from presurgery to 24 months postsurgery. At 24 months, 70% of patients were satisfied with their sports participation. Active knee flexion (p < 0.0001) and extension (p < 0.0001) ROM significantly improved over time, as did the limb symmetry indices (LSIs) for the SHD (p < 0.0001), THD (p < 0.0001), peak knee extensor (p < 0.0001) and flexor (p = 0.012) torque. While LSIs for the SHD, THD and knee flexor strength tended to plateau by 12 months, knee extensor strength continued to improve from 12 to 24 months. CONCLUSIONS: The majority of patients undergoing modern MLKR surgical techniques and rehabilitation can achieve excellent knee function, with low complication rates. LEVEL OF EVIDENCE: Level IV.

[Study of the growth temperature of ocular surface microorganisms in norm and in infectious keratitis]. / Izuchenie temperaturnykh uslovii rosta mikroorganizmov glaznoi poverkhnosti v norme i pri infektsionnykh keratitakh.

Standard bacteriological examinations, which involve culturing microorganisms at 37 °C, are commonly used in clinical practice for diagnosing infectious diseases. However, the growth temperature of microorganisms on the ocular surface (OS) during infectious keratitis (IK) may not coincide with the laboratory standard, which is due to the characteristic features of heat exchange in the eye. PURPOSE: This exploratory study examines the distribution and properties of OS microorganisms isolated under different temperature cultivation conditions in patients with IK and healthy volunteers without ophthalmic pathology. MATERIAL AND METHODS: Fifteen participants were divided into two groups. Group 1 (n=10) consisted of patients with signs of unilateral infectious keratitis, while group 2 (n=5) served as the control group. A novel microbiological method was employed to isolate pure cultures of microorganisms. This method involved cultivating microorganisms at two temperature regimes (37 °C and 24 °C) and subsequently identifying them using biochemical, immunological, and physicochemical techniques, including mass spectrometry. Scanning electron microscopy (SEM) with lanthanide staining used as the reference method. The temperature status of the ocular surface was assessed using non-contact infrared thermography. RESULTS: The study demonstrated the presence of psychrotolerant microorganisms on the ocular surface, which exhibited growth at a relatively low temperature of 24 °C. These psychrotolerant microorganisms were found to be isolated from the ocular surface displaying signs of temperature dysregulation. Among such microorganisms are Acinetobacter lwoffii, Achromobacter xylosoxidans, Bacillus licheniformis, Enterococcus faecalis, Klebsiella oxytoca, Klebsiella pneumoniae, Micrococcus luteus, Pseudomonas luteola, Streptococcus spp. CONCLUSION: When identifying the causative agent of infectious keratitis, it is crucial to consider the divergence of growth temperature of ocular surface microorganisms. The presence of psychrotolerant microorganisms on the ocular surface, which can effectively grow at room temperature, should be taken into account, especially in cases of temperature dysregulation.

System-agnostic prediction of pharmaceutical excipient miscibility via computing-as-a-service and experimental validation.

We applied computing-as-a-service to the unattended system-agnostic miscibility prediction of the pharmaceutical surfactants, Vitamin E TPGS and Tween 80, with Copovidone VA64 polymer at temperature relevant for the pharmaceutical hot melt extrusion process. The computations were performed in lieu of running exhaustive hot melt extrusion experiments to identify surfactant-polymer miscibility limits. The computing scheme involved a massively parallelized architecture for molecular dynamics and free energy perturbation from which binodal, spinodal, and mechanical mixture critical points were detected on molar Gibbs free energy profiles at 180 °C. We established tight agreement between the computed stability (miscibility) limits of 9.0 and 10.0 wt% vs. the experimental 7 and 9 wt% for the Vitamin E TPGS and Tween 80 systems, respectively, and identified different destabilizing mechanisms applicable to each system. This paradigm supports that computational stability prediction may serve as a physically meaningful, resource-efficient, and operationally sensible digital twin to experimental screening tests of pharmaceutical systems. This approach is also relevant to amorphous solid dispersion drug delivery systems, as it can identify critical stability points of active pharmaceutical ingredient/excipient mixtures.

Impact of copper sulphate treatment on cyanobacterial blooms and subsequent water quality risks.

Control of algal blooms and associated biologically-induced water quality risks in drinking reservoirs is problematic. Copper sulphate (CuSO4) treatment is one intervention that has been utilised for >100 years. Evidence indicates a favourable short-term reduction in Cyanobacterial biomass (e.g. bloom termination), but here we indicate that it may also increase longer-term water quality risk. In 2022, we investigated the impacts of CuSO4 spraying on Cyanobacterial communities and nutrient levels within a drinking water supply reservoir using environmental DNA (eDNA) to assess community shifts, alongside monitoring nutrient fractions, orthophosphate (OP) and total phosphate (TP), post-treatment. CuSO4 application successfully reduced Cyanobacterial abundance, however elimination of Cyanobacteria resulted in a shift in bacterial dominance favouring Planctomycetota throughout the summer and a combination of Actinobacteriota and Verrucomicrobiota, throughout autumn. As Cyanobacterial abundance recovered post-treatment, Cyanobacterial genera demonstrated greater diversity compared to only three Cyanobacterial genera present across samples pre-treatment, and included taxa associated with water quality risk (e.g. taste and odour (T&O) metabolite and toxin producers). The increase in Cyanobacteria post-treatment was attributed to an increase in biologically available nutrients, primarily a significant increase in OP. Overall, findings suggest that the significant shift in biodiversity likely induces a less stable ecosystem with greater plasticity of response to changing environmental and biogeochemical variables. Legacy implications of CuSO4 spraying, in terms of shifts in ecosystem and nutrient balance over time, may have implications for drinking water quality, but importantly also for reservoir management options. As such, the effects of CuSO4 spraying should be considered carefully before consideration as a contender for in-reservoir biological control.

Prognostic factors and the value of radiographic osteoarthritis for persistent complaints after referral for ankle radiography.

BACKGROUND: Ankle symptoms are a common reason to consult the general practitioner and often persist for years. In a population referred for ankle radiography, the prevalence of radiographic osteoarthritis (OA) is substantial, but its additional predictive value for persistent symptoms is unknown. Therefore, we examined the prognosis of symptoms 2-3 years after referral for ankle radiography, assessed clinical prognostic factors, and the additional predictive value of radiographic OA for persistent ankle complaints. METHODS: We included 893 adults referred for ankle radiography and studied the following candidate prognostic factors at baseline: age, sex, body mass index (BMI), referral for chronic complaints (>3 months), pain during activity (NRS-11) and presence of stiffness and functional loss as predominant symptom. X-rays were scored for radiographic OA. After 2-3 years participants were invited for a follow-up questionnaire including persistence of ankle complaints. To assess prognostic factors for persistent complaints, uni- and multivariable logistic regression were used. RESULTS: Of the 194 responders at follow-up, ankle complaints persisted in 71(36.6 %). BMI (OR 1.08; 95 % CI 1.01-1.15), stiffness as predominant symptom (OR 1.69; 95 % CI 0.89-3.21), and chronic complaints (OR 2.84; 95 % CI 1.45-5.57) were in the initial model for persistent complaints (AUC=0.69). After adding radiographic OA (OR 2.36; 95 % CI 1.01-5.50), the AUC of the final model became 0.70. CONCLUSION: Ankle complaints persist in a considerable proportion of patients 2-3 years after referral for ankle radiography. BMI, chronic complaints and radiographic OA are prognostic factors for persistent complaints, but the additional predictive value of radiographic OA on top of clinical factors is negligible.

[Liver transplantation program at the Burnasyan Federal Biophysical Center: experience in 500 procedures]. / Programma transplantatsii pecheni v Federal'nom meditsinskom biofizicheskom tsentre im. A.I. Burnazyana: opyt 500 operatsii.

OBJECTIVE: To analyze the features and outcomes of 500 liver transplantations in adults over a 12-year period. MATERIALS AND METHODS: The study included data on 500 liver transplantations between May 2010 and April 2023. We analyzed 483 adults who underwent transplantation and 438 candidates for this procedure. All data were obtained from local liver transplantation registry. Clinical outcomes were recorded as of June 1, 2023. Statistical analysis was performed using the Statistica 12 (StatSoft Inc., USA) and Jamovi version 2.3.21.0 software (Jamovi project). RESULTS: Among 438 patients in the waiting list between January 2012 and May 2023, liver transplantation was performed in 198 (45%) cases including 27 (6%) transplantations from living-related donors and 37 (8%) procedures in other centers. There were 109 (25%) deaths. The 1- and 3-year survival rates were 81% (95% CI 76-85%) and 50% (95% CI 42-59%), respectively. Organs from deceased donors (n=134, 27%) and living-related donors (n=366, 73%) were used for transplantations. Redo transplantations were necessary in 21 (4%) cases. The median age of recipients was 45 years (range 18-72), median MELD-Na score - 16 (range 6-43). The most common indications for transplantation were viral cirrhosis (37%), cholestatic liver disease (16%), and hepatocellular carcinoma (14%). Monotherapy with calcineurin inhibitors was performed in 39% of cases, combination of calcineurin inhibitors and glucocorticoids, antimetabolites or mTOR inhibitors - 52%, three-component schemes - 8% of cases. Annual, 5- and 7-year survival rates of recipients after primary transplantation were 87% (95% CI: 84-90%), 79% (95% CI: 75-83%) and 75% (95% CI: 70-80%), respectively. In case of liver transplantation from living-related donors, these values were 89% (95% CI: 86-92%), 84% (95% CI: 80-88%) and 80% (95% CI: 75-85%), after transplantation from deceased donors - 81% (95% CI: 74-88%), 66% (95% CI: 57-76%) and 58% (95% CI: 45-72%), respectively. CONCLUSION: Liver transplantation is highly effective for patients with diffuse and focal liver diseases. Living donors not only significantly improve availability of this technology, but also provide substantial advantages in outcomes compared to liver transplantation from deceased donors, reducing the likelihood of recipient mortality by 10% after one post-transplantation year and by more than 20% after five years.

A preliminary study on the feasibility of two different cow-calf contact systems in a pasture-based, seasonal calving dairy system: effects on cow production and health.

Internationally, consumer dissatisfaction with cow-calf separation at birth has led to increased interest in alternative calf-rearing methods, specifically cow-calf contact (CCC) systems. The objectives of this preliminary study were to estimate whether CCC could be incorporated into an Irish spring-calving, pasture-based system, and to investigate the effects on cow milk production and health. Three systems were compared: the conventional Irish system (CONV;18 cows), cow and calf were separated < 1 h postbirth, cows were pasture-based and milked twice-a-day; a full-time access system (FT;14 cows), cow and calf were allowed constant, unrestricted access, were pasture-based, and cows were milked twice-a-day; and a part-time access system (PT;18 cows), cow and calf had unrestricted access when indoors at night, cows grazed outdoors by day while calves remained indoors, and cows were milked once-a-day in the morning. Cows were blocked and balanced across the three systems by previous lactation machine milk yield (MMY), BW, and body condition score (BCS). Following an 8-week CCC period, all calves were weaned (FT and PT underwent a 7-d gradual weaning and separation process) and all cows were milked twice-a-day. Cow MMY was recorded daily and milk composition was recorded weekly; milk data were analysed from weeks 1 to 8 (CCC period), weeks 9 to 35 (post-CCC period), and weeks 1 to 35 (cumulative lactation). Cow BW and BCS were taken weekly for weeks 1-12, and at the end of the lactation. During the CCC period, all systems differed (P < 0.001) in MMY (mean ± SEM; 24.0, 13.6, and 10.3 ± 0.50 kg/d for CONV, FT, and PT cows, respectively). After the CCC period, CONV MMY (20.2 ± 0.48 kg/d) remained higher (P < 0.001) than the FT (16.6 kg/d) and PT cows (15.7 kg/d). The FT and PT cows yielded 24 and 31% less in cumulative lactation MMY and 26 and 35% less in cumulative lactation milk solids yield, respectively, compared to CONV (5 072 ± 97.0 kg and 450 ± 8.7 kg). During the CCC period, somatic cell score was higher (P = 0.030) in PT cows (5.15 ± 0.118) compared to FT cows (4.70 ± 0.118), while CONV (4.94 ± 0.118) were inconclusive to both. The PT cows (523 ± 4.9 and 520 ± 6.8 kg) were heavier than the CONV (474 ± 4.9 and 479 ± 6.8 kg) and FT (488 ± 4.9 and 487 ± 6.8 kg) cows at week 4 and week 8 (both P < 0.001). The PT cows had higher BCS than CONV and FT at all observed times. This preliminary research suggests that although CCC was incorporated without impacting cow health, the two CCC systems investigated negatively affected cow production.

Cyclic tachyplesin I kills proliferative, non-proliferative and drug-resistant melanoma cells without inducing resistance.

Acquired drug resistance is the major cause for disease recurrence in cancer patients, and this is particularly true for patients with metastatic melanoma that carry a BRAF V600E mutation. To address this problem, we investigated cyclic membrane-active peptides as an alternative therapeutic modality to kill drug-tolerant and resistant melanoma cells to avoid acquired drug resistance. We selected two stable cyclic peptides (cTI and cGm), previously shown to have anti-melanoma properties, and compared them with dabrafenib, a drug used to treat cancer patients with the BRAF V600E mutation. The peptides act via a fast membrane-permeabilizing mechanism and kill metastatic melanoma cells that are sensitive, tolerant, or resistant to dabrafenib. Melanoma cells do not become resistant to long-term treatment with cTI, nor do they evolve their lipid membrane composition, as measured by lipidomic and proteomic studies. In vivo studies in mice demonstrated that the combination treatment of cTI and dabrafenib resulted in fewer metastases and improved overall survival. Such cyclic membrane-active peptides are thus well suited as templates to design new anticancer therapeutic strategies.

Acute liver failure: Management update and prognosis.

Acute liver failure is a rare but serious syndrome, with an incidence of approximately 2,000 to 3,000 cases per year in North America. Its pathophysiology and clinical course vary, depending on the cause of the primary liver injury, and can lead to high morbidity and mortality or the need for liver transplantation, despite available therapies. This syndrome involves excessive activation of the immune system, with damage in other organs, contributing to its high mortality rate. The most accepted definition includes liver injury with hepatic encephalopathy and coagulopathy within the past 26 weeks in a patient with no previous liver disease. The main causes are paracetamol poisoning, viral hepatitis, and drug-induced liver injury, among others. Identifying the cause is crucial, given that it influences prognosis and treatment. Survival has improved with supportive measures, intensive therapy, complication prevention, and the use of medications, such as N-acetylcysteine. Liver transplantation is a curative option for nonresponders to medical treatment, but adequate evaluation of transplantation timing is vital for improving results. Factors such as patient age, underlying cause, and severity of organ failure influence the post-transplant outcomes and survival.

Effects of corn grain processing and phosphorus content in calf starters on intake, growth performance, nutrient digestibility, blood metabolites, and urinary purine derivatives.

Corn grain with a high phosphorus (P) content (mainly in the form of phytate-P) may need to be processed to improve the digestibility of nutrients for young calves. Processing corn grains can improve the accessibility of phytate-P to the rumen enzymes and increase the bioavailability of P, which benefits the growth and development of calves. The objective of this study was to investigate the effects of feeding starter diets with steam-flaked corn (SFC) compared with ground corn (GC) with 2 P contents of 0.4% and 0.7% DM basis on intake, growth performance, nutrient digestibility, blood metabolites and urinary purine derivatives in dairy calves. A total of 48 female Holstein dairy calves (3 d old; average initial weight 39.7 ± 3.9 kg) were randomly assigned to a 2 × 2 factorial arrangement of treatments (12 calves/treatment) in a randomized complete block design. The treatment groups were: 1) a starter diet of GC with 0.4% P (GC-0.4P); 2) a starter diet of GC with 0.7% P (GC-0.7P); 3) a starter diet of SFC with 0.4% P (SFC-0.4P); 4) a starter diet of SFC with 0.7% P (SFC-0.7P). Calves received 6 L/d of transition milk on d 2-3 and 5 L/d of whole milk on d 4-30, which was increased to 7 L/d on d 31-45, then decreased to 5 L/d on d 46-60 and reduced to a single feeding of 2 L on d 61-62. All calves had free access to starter feed and water. All calves were weaned on d 63 and remained in the study until d 83. Rumen fluid samples were collected on d 38 (pre-weaning) and d 76 (post-weaning). Blood samples were collected on d 40 and 80 and urine samples were collected on 4 consecutive days from d 79 to 82 to analyze urinary excretion of PD. The phytate-P content ranged from 0.23 to 0.17 for GC and SFC, respectively. In particular, the interaction between corn processing method and P content showed that the SFC-0.7P diets had a greater intake of starter feed during the pre- and post-weaning periods compared with the other experimental groups. In addition, calves fed the SFC-0.7P diet had greater average daily gain, body weight, withers height at weaning, better organic matter digestibility, higher blood ß-hydroxybutyrate levels and higher microbial protein synthesis compared with all other groups. Feeding the SFC diet also resulted in improved feed efficiency, improved P digestibility and a tendency toward a lower rumen pH, albeit with a tendency toward an increase in blood glucose concentration during the pre-weaning period. In addition, the inclusion of 0.7% P to the starter diet resulted in increased fiber digestibility and a slight improvement in growth performance, which was particularly evident in hip height. Overall, the inclusion of SFC in the calf starter diet, especially in combination with a 0.7% DM basis P supplement, improved growth performance and nutrient utilization in dairy calves compared with GC.

Leveraging binding pose metadynamics to optimise target fishing predictions for three diverse ligands and their true targets.

Computational target fishing plays an important role in target identification, particularly in drug discovery campaigns utilizing phenotypic screening. Numerous approaches exist to predict potential targets for a given ligand, but true targets may be inconsistently ranked. More advanced simulation methods may provide benefit in such cases by reranking these initial predictions. We evaluated the ability of binding pose metadynamics to improve the predicted rankings for three diverse ligands and their six true targets. Initial predictions using pharmacophore mapping showed no true targets ranked in the top 50 and two targets each ranked within the 50-100, 100-150, and 250-300 ranges respectively. Following binding pose metadynamics, ranking of true targets improved for four out of the six targets and included the highest ranked predictions overall, while rankings deteriorated for two targets. The revised rankings predicted two true targets ranked within the top 50, and one target each within the 50-100, 100-150, 150-200, and 200-250 ranges respectively. The findings of this study demonstrate that binding pose metadynamics may be of benefit in refining initial predictions from structure-based target fishing algorithms, thereby improving the efficiency of the target identification process in drug discovery efforts.

The Relationship Between Men's Sociosexuality, Drinking Intake, and Blackouts.

Background: Sociosexuality-attitudes, behaviors, and desires related to casual sex-partly predicts drinking behavior in both men and women because drinking is thought to facilitate interactions that lead to casual sex. It follows that sociosexuality would predict drinking intake (e.g., quantity consumed)-but perhaps not drinking consequences (e.g., blacking out)-on the premise that drinking large quantities with high frequency (but not to such high degrees/levels of intoxication that negative consequences occur) would facilitate casual sex. Objectives: This set of studies evaluated whether baseline measures of sociosexuality predict drinking intake (i.e., frequency, quantity, and binge drinking) but not experiencing blacking out at follow-up in two samples (Study 1, N = 172; Study 2, N = 1,038) of college-aged men. Results: As predicted, men's sociosexuality prospectively predicted drinking frequency, quantity, and binge drinking. Contrary to our predictions, men's sociosexuality also predicted blacking out. Conclusions: College men's drinking interventions should be tailored to high-risk groups and consider individual differences like sociosexuality.

Inclusive Approaches for Measuring Demographics of Underrepresented Populations in STEM and Biomedical Research Training Programs.

As federal strategic plans prioritize increasing diversity within the biomedical workforce, and STEM training and outreach programs seek to recruit and retain students from historically underrepresented populations, there is a need for interrogation of traditional demographic descriptors and careful consideration of best practices for obtaining demographic data. To accelerate this work, equity-focused researchers and leaders from STEM programs convened to examine approaches for measuring demographic variables. Gender, race/ethnicity, disability, and disadvantaged background were prioritized given their focus by federal funding agencies. Categories of sex minority, sexual (orientation) minority, and gender minority (SSGM) should be included in demographic measures collected by STEM programs, consistent with recommendations from White House Executive Orders and federal reports. Our manuscript offers operationalized phrasing for demographic questions and recommendations for use across student-serving programs. Inclusive demographics permit the identification of individuals who are being excluded, marginalized, or improperly aggregated, increasing capacity to address inequities in biomedical research training. As trainees do not enter training programs with equal access, accommodations, or preparation, inclusive demographic measures can welcome trainees and inform a nuanced set of program outcomes that facilitate research on intersectionality to support the recruitment and retention of underrepresented students in biomedical research.

Health system costs of providing outpatient care for diabetes in people with TB in the Philippines.

BACKGROUND: Diabetes mellitus (DM) is a known risk factor for active TB. A key activity in the Philippines is to integrate TB services with other disease programmes, with a target of DM screening in 90% of TB cases. However, costs of providing DM outpatient services for TB patients are not well known. METHODS: We estimated the costs of providing integrated DM outpatient services within TB services from the health system perspective. Resources for outpatient DM services were valued using the bottom-up approach for capital goods, staff time and consumables. Resource quantities were obtained by interviewing 60 healthcare professionals in 11 health facilities in the Philippines. RESULTS: The mean cost per service ranged from USD0.53 for DM risk assessment to USD23.72 for oral glucose tolerance test. The cost per case detected for different algorithms varied from USD17.43 to USD80.81. The monthly cost per patient was estimated at USD8.95 to USD12.36. CONCLUSION: Our study provides the first estimates of costs for providing integrated DM outpatient services and TB care in a low- and middle-income country. The costs of DM detection in TB patients suggests that it may be useful to further investigate the cost-effectiveness and affordability of service delivery.

CONTEXTE: Le diabète (DM) est un facteur de risque bien établi pour la TB active. Aux Philippines, l'une des principales initiatives est d'intégrer les services de lutte contre la TB dans d'autres programmes de santé, dans le but de dépister le DM chez 90% des patients atteints de TB. Cependant, les coûts des services ambulatoires de traitement du DM pour les patients atteints de TB ne sont pas clairement définis. MÉTHODES: Nous avons évalué les coûts des services ambulatoires intégrés pour le traitement du DM dans le cadre des services de lutte contre la TB, du point de vue du système de santé. Les ressources pour les services ambulatoires de DM ont été évaluées en utilisant l'approche ascendante pour les biens d'équipement, le temps du personnel et les consommables. Les quantités de ressources ont été recueillies en interrogeant 60 professionnels de la santé dans 11 établissements de santé aux Philippines. CONCLUSION: Notre étude présente les premières estimations des coûts des services ambulatoires intégrés pour le traitement du DM et de soins de la TB dans un pays à revenu faible ou intermédiaire. Il est suggéré d'approfondir l'étude du rapport coût-efficacité et de l'accessibilité des services de détection de la DM chez les patients atteints de TB, compte tenu des coûts impliqués.

Evaluation of oral health status and immunological parameters of hospitalized COVID-19 patients during acute and recovery phases: A randomized clinical trial.

Background/purpose: It is known that COVID-19 patients show many clinical oral symptoms due to the immunological mechanisms triggered by the virus. Aim of this study is to analyze the antibody response to SARS-CoV-2, and to evaluate the oral health status of hospitalized patients. Materials and methods: 160 patients with COVID-19 confirmed by SARS-CoV-2-specific RT-PCR testing and 160 healthy volunteers (HI) with similar age, gender and systemic status were included to compare the bio-chemical and oral manifestations. Oropharyngeal swab specimens were collected to evaluate the salivary interleukins (IL-1, IL-6, IL-10) and immunoglobulins (sIgA, sIgG, sIgM). Oral findings (DMFT, plaque index, salivary flow rate), socio-demographic information and systemic conditions were also recorded. Chi-square, Mann-Whitney U and Spearman's ratio tests were applied to determine the possible correlations between the factors (P = 0.05). Results: The mean DMFT scores of COVID-19 patients (12.71 ± 7.3) were significantly higher than the HI (7.39 ± 2.8), whereas cases of total or partial edentulism were more common among COVID-19 patients (P < 0.05). While plaque index scores were similar for both groups (P > 0.05), salivary parameters were found statistically different (P < 0.05). Severe and moderate cases showed higher proinflammatory interleukin levels (IL-1 = 68.74 pg/ml, IL-6 = 53.31 pg/ml) amongst all (P < 0.05). While secretory immunoglobulins were almost depleted at baseline, (sIgA = 0.11 mg/ml, sIgG = 0.21 mg/ml, sIgM = 0.08 mg/ml) they reached to threshold levels after 4 weeks. Conclusion: Higher proinflammatory interleukin levels indicated that traces of ongoing "Cytokine Storm" in COVID-19 patients which can also be observed in oral environment. Poor oral hygiene and malnutrition due to edentulism can pave the way for having a severe COVID-19 infection.

Cross-Validation of Lipid Structure Assignment Using Orthogonal Ion Activation Modalities on the Same Mass Spectrometer.

The onset and progression of cancer is associated with changes in the composition of the lipidome. Therefore, better understanding of the molecular mechanisms of these disease states requires detailed structural characterization of the individual lipids within the complex cellular milieu. Recently, changes in the unsaturation profile of membrane lipids have been observed in cancer cells and tissues, but assigning the position(s) of carbon-carbon double bonds in fatty acyl chains carried by membrane phospholipids, including the resolution of lipid regioisomers, has proven analytically challenging. Conventional tandem mass spectrometry approaches based on collision-induced dissociation of ionized glycerophospholipids do not yield spectra that are indicative of the location(s) of carbon-carbon double bonds. Ozone-induced dissociation (OzID) and ultraviolet photodissociation (UVPD) have emerged as alternative ion activation modalities wherein diagnostic product ions can enable de novo assignment of position(s) of unsaturation based on predictable fragmentation behaviors. Here, for the first time, OzID and UVPD (193 nm) mass spectra are acquired on the same mass spectrometer to evaluate the relative performance of the two modalities for lipid identification and to interrogate the respective fragmentation pathways under comparable conditions. Based on investigations of lipid standards, fragmentation rules for each technique are expanded to increase confidence in structural assignments and exclude potential false positives. Parallel application of both methods to unsaturated phosphatidylcholines extracted from isogenic colorectal cancer cell lines provides high confidence in the assignment of multiple double bond isomers in these samples and cross-validates relative changes in isomer abundance.

[Sleep disorders during pregnancy]. / Narusheniya sna pri beremennosti.

Pregnancy is associated with a number of physiological changes in a woman's body, which in turn affect the quality and duration of sleep. According to research, insomnia and other sleep disorders are associated with a high risk of adverse pregnancy outcomes, as well as postpartum complications. Understanding the mechanisms of sleep disorders during pregnancy is necessary to form an integrated approach in the management of this group of patients. The appointment of medicinal and non-medicinal therapies, as well as general recommendations for lifestyle correction in order to treat sleep disorders, is focused on the safe and prolific effect of a particular drug on the mother and fetus. This review also examined the safety profile of commonly used groups of drugs for sleep disorders during pregnancy.