Megalencephaly secondary to a novel germline missense variant p.Asp322Tyr in AKT3 associated with growth hormone deficiency and central hypothyroidism: A case report.

Germline gain of function variations in the AKT3 gene cause brain overgrowth syndrome with megalencephaly and diffuse bilateral cortical malformations. Here we report a child with megalencephaly, who is a carrier of a novel heterozygous missense variant in the AKT3 gene NM_005465.7:c.964G>T,p.Asp322Tyr. The phenotype of this patient is associated with pituitary deficiencies diagnosed at 2 years of age: growth hormone (GH) deficiency responsible for growth delay and central hypothyroidism. After 6 months of GH treatment, intracranial hypertension was noted, confirmed by the observation of papilledema and increased intracranial pressure, requiring the initiation of acetazolamide treatment and the discontinuation of GH treatment. This is the second reported patient described with megalencephaly and AKT3 gene variant associated with GH deficiency . Other endocrine disorders have also been reported in few cases with hypothyroidism and hypoglycemia. Pituitary deficiency may be a part of the of megalencephaly phenotype secondary to germline variant in the AKT3 gene. Special attention should be paid to growth in these patients and search for endocrine deficiency is necessary in case of growth retardation or hypoglycemia.

Open-source deep learning-based air-void detection algorithm for concrete microscopic images.

Analysing concrete microscopic images is difficult because of its highly heterogeneous composition and the different scales involved. This article presents an open-source deep learning-based algorithm dedicated to air-void detection in concrete microscopic images. The model, whose strategy is presented alongside concrete compositions information, is built using the Mask R-CNN model. Model performances are then discussed and compared to the manual air-void enhancement technique. Finally, the selected open-source strategy is exposed. Overall, the model shows a good precision (mAP = 0.6452), and the predicted air void percentage agrees with experimental measurements highlighting the model's potential to assess concrete durability in the future.

Analyzing concrete microscopic images is difficult because of its highly heterogeneous composition and the different scales involved, e.g. cement paste, sand, and aggregates are the major phases at a microscopic scale. However, characterizing concrete microstructure is of paramount importance to assess its mechanical properties and durability. For example, air voids decrease the mechanical properties but can increase the resistance to freeze-thaw if correctly distributed and of small size. This article presents an open-source deep learning-based algorithm dedicated to air-void detection in concrete microscopic images. The model, whose strategy is presented alongside concrete compositions information, is built using the Mask R-CNN model. Model performances are then discussed and compared to the manual air-void enhancement technique, which involves coloring concrete surfaces and filling air voids with fine powder before taking images. Finally, the selected open-source strategy is exposed. Overall, the model shows a good precision (mAP = 0.6452), and the predicted air void percentage agrees with experimental measurements highlighting the model's potential to assess concrete durability in the future.

[Early intervention in bipolar affective disorders: Why, when and how]. / Intervenir précocement dans les stades débutants du trouble bipolaire : pourquoi, quand et comment.

OBJECTIVES: Bipolar disorder (BD) is a chronic and severe psychiatric disease. There are often significant delays prior to diagnosis, and only 30 to 40 % of patients will experience complete remission. Since BD occurs most often at a young age, the disorder can seriously obstruct future socio-professional development and integration. Vulnerability-stress model of BD is considered to be the result of an interaction between vulnerability genes and environmental risk factors, which leads to the onset of the disorder most often in late adolescence or early adulthood. The clinical "staging" model of BD situates the subject in a clinical continuum of varying degrees of severity (at-risk status, first episode, full-blown BD). Given the demonstrated effectiveness of early intervention in the early stages of psychotic disorder, we posit that early intervention for early stages of BD (i.e. at-risk status and first episode mania or hypomania) would reduce the duration of untreated illness and optimize the chances of therapeutic response and recovery. METHODS: We conducted a narrative review of the literature to gather updated data on: (1) features of early stages: risk factors, at-risk symptoms, clinical specificities of the first manic episode; (2) early screening: targeted populations and psychometric tools; (3) early treatment: settings and therapeutic approaches for the early stages of BD. RESULTS: (1) Features of early stages: among genetic risk factors, we highlighted the diagnosis of BD in relatives and affective temperament including as cyclothymic, depressive, anxious and dysphoric. Regarding prenatal environmental risk, we identified peripartum factors such as maternal stress, smoking and viral infections, prematurity and cesarean delivery. Later in the neurodevelopmental course, stressful events and child psychiatric disorders are recognized as increasing the risk of developing BD in adolescence. At-risk symptoms could be classified as "distal" with early but aspecific expressions including anxiety, depression, sleep disturbance, decreased cognitive performance, and more specific "proximal" symptoms which correspond to subsyndromic hypomanic symptoms that increase in intensity as the first episode of BD approaches. Specific clinical expressions have been described to assess the risk of BD in individuals with depression. Irritability, mixed and psychotic features are often observed in the first manic episode. (2) Early screening: some individuals with higher risk need special attention for screening, such as children of people with BD. Indeed, it is shown that children with at least one parent with BD have around 50 % risk of developing BD during adolescence or early adulthood. Groups of individuals presenting other risk factors, experiencing an early stage of psychosis or depressive disorders should also be considered as targeted populations for BD screening. Three questionnaires have been validated to screen for the presence of at-risk symptoms of BD: the Hypomanic Personality Scale, the Child Behavior Checklist-Paediatric Bipolar Disorder, and the General Behavior Inventory. In parallel, ultra-high risk criteria for bipolar affective disorder ("bipolar at-risk") distinguishing three categories of at-risk states for BD have been developed. (3) Early treatment: clinical overlap between first psychotic and manic episode and the various trajectories of the at-risk status have led early intervention services (EIS) for psychosis to reach out for people with an early stage of BD. EIS offers complete biopsychosocial evaluations involving a psychiatric examination, semi-structured interviews, neuropsychological assessments and complementary biological and neuroimaging investigations. Key components of EIS are a youth-friendly approach, specialized and intensive care and client-centered case management model. Pharmaceutical treatments for at-risk individuals are essentially symptomatic, while guidelines recommend the use of a non-antipsychotic mood stabilizer as first-line monotherapy for the first manic or hypomanic episode. Non-pharmacological approaches including psychoeducation, psychotherapy and rehabilitation have proven efficacy and should be considered for both at-risk and first episode of BD. CONCLUSIONS: EIS for psychosis might consider developing and implementing screening and treatment approaches for individuals experiencing an early stage of BD. Several opportunities for progress on early intervention in the early stages of BD can be drawn. Training first-line practitioners to identify at-risk subjects would be relevant to optimize screening of this population. Biomarkers including functional and structural imaging measures of specific cortical regions and inflammation proteins including IL-6 rates constitute promising leads for predicting the risk of transition to full-blown BD. From a therapeutic perspective, the use of neuroprotective agents such as folic acid has shown particularly encouraging results in delaying the emergence of BD. Large-scale studies and long-term follow-up are still needed to achieve consensus in the use of screening and treatment tools. The development of specific recommendations for the early stages of BD is warranted.

Long term functional outcomes after minimally invasive surgical decompression in upper limb chronic exertional compartment syndrome in 30 patients.

Chronic exertional compartment syndrome (CECS) of the upper limbs is less well known than its equivalent in the lower limbs, thus its diagnosis is often delayed. Our goals were to evaluate the impact of CECS on activities of daily living and work-related activities and to report the functional outcomes after minimally invasive fasciotomy. This was a retrospective study of patients with CECS of the upper limb who were operated at two hospitals between 2008 and 2019. Thirty patients were reviewed an average of 5 years after minimally invasive fasciotomy: 26 had CECS of the forearm, 3 of the thenar compartment and 1 of the first interosseous compartment. For the evaluation, patients were asked to assess their pain on a visual analog scale (VAS), complete the QuickDASH questionnaire and rate their satisfaction with the outcome. Preoperative pain on the VAS was 7.45/10 with a negative impact on activities of daily living in 97% of patients, and on work-related activities in 77% of patients with 17% requiring a career change. The mean time to surgical treatment was 5 years. The mean QuickDASH at the final assessment was 6.0 (0-31.8) with a significant decrease in pain on VAS of 1.9/10 (p < 0.01). Seventy-seven percent of patients had very good results while 13% had good results. Full healing was achieved in 63% of patients and physical performance improved in 50%. Seventy-seven percent of patients were either satisfied or very satisfied with the outcome. One patient had a recurrence requiring surgical revision. CECS affects athletes of all levels and impacts both activities of daily living and work-related activities. We need to greatly expand our education and prevention efforts for CECS. Mini-open fasciotomy yields good results.

Parkinsonian gait in elderly people: Significance of the threshold value of two and more falls per year.

OBJECTIVES: Parkinsonism in the elderly presents a major risk factor for recurrent falls (2 and more falls per year), which is associated with increased morbidity. The main objective was to investigate explanatory variables relating to the risk of being recurrent fallers (RF) in persons with parkinsonian gait. METHODS: Seventy-nine among 172 eligible persons were enrolled in this prospective study, the findings of which were analyzed at 12 months. Motor and non-motor features, as well as follow-up interviews to identify falls, loss of ability to walk, fluctuating cognition, traumatic falls, all-cause hospitalizations and deaths were collated and results compared between non RF (zero and one fall per year) and RF. Bayesian model averaging was used to predict the probability of patients being RF from their medical history as well as from cognitive assessment, gait velocity, vision and posture. RESULTS: N=79, 0.58 men, 50% had Parkinson's disease, 14% other neurodegenerative parkinsonian syndrome, 23% vascular parkinsonism and 13% Lewy body disease, 58% were RF. Median age 81.2 years and median MMSE 25/30. A history of falls and of hallucinations, median odds ratio respectively 9.06 (CI 2.34-38.22), 4.21 (CI 1.04-18.67) were associated with the highest odds ratios along with fluctuating cognition and abnormal posture. Two or more falls a year was a relevant threshold to distinguish a population with a high risk of comorbidity. CONCLUSION: The whole history of falls, hallucinations and fluctuating cognition can be considered predictive of recurrent falls in elderly people with parkinsonian gait and provide a tracking tool for patient management.

A randomized controlled double-blind study of rotigotine on neuropsychiatric symptoms in de novo PD.

Management of apathy, depression and anxiety in Parkinson's disease (PD) represents a challenge. Dopamine agonists have been suggested to be effective. This multicenter, randomized (1:1), double-blind study assessed the 6-month effect of rotigotine versus placebo on apathy, depression and anxiety in de novo PD. The primary outcome was the change of apathy, measured with the LARS. The secondary outcomes were the change in depression and anxiety, measured with BDI-2 and STAI-trait and state. Forty-eight drug-naive PD patients were included. The primary outcome was not reached, with a surprisingly high placebo effect on apathy (60%). There was no significant difference in the change of depression at 6 months between rotigotine and placebo. Trait-anxiety was significantly improved by rotigotine compared to placebo (p = 0.04). Compared to placebo, low dose rotigotine significantly improved trait anxiety, but not apathy and depression. The major placebo effect on apathy points towards the importance of a multidisciplinary and tight follow-up in the management of neuropsychiatric symptoms.

Influência da restrição alimentar e do estresse térmico sobre parâmetros fisiológicos em ovinos / [Influence of food restriction and heat stress on physiological parameters in sheep]

Objetivou-se avaliar as alterações fisiológicas de ovinos submetidos à restrição alimentar, expostos à radiação solar e à sombra. Dez borregas mestiças foram divididas igualmente em dois grupos: grupo radiação solar - GRS, animais expostos ao sol durante o dia; e grupo sombra - GS, animais alocados dentro de um galpão à sombra. Nos seis dias iniciais de experimento, os animais foram submetidos à restrição alimentar, com acesso apenas à água, já expostos ao sol ou à sombra. Nos seis dias subsequentes, foi ofertada dieta composta por ração e feno de alfafa (3%PV). Os parâmetros avaliados foram frequência respiratória (FR), temperatura retal (TR), ß-hidroxibutirato (BHB), pH urinário, ingestão de matéria seca (IMS) e dados bioclimáticos (temperatura, umidade relativa do ar e índice de temperatura e umidade - ITU). A FR foi o parâmetro em que houve maior diferença significativa entre os grupos (p<0,05). O balanço energético negativo foi constatado em todos os animais (BHB>0,8mmol/L; pH<7,0). Ovelhas que sofrem restrição alimentar durante períodos de alta temperatura e umidade têm menor frequência respiratória e temperatura interna, independentemente de estar na sombra ou pleno sol. Porém, quando normalizado a oferta de alimento as ovelhas em pleno sol têm menor ingestão de matéria seca.(AU)

We aimed to evaluate physiological changes in sheep submitted to food restriction, exposed to the sun or shade. Ten ewe lambs were equally divided into two groups: Sun Radiation Group - GRS, exposed to sun during day hours, and Shade Group - GS, with animals placed inside a barn. In the first six days of experiment, animals were submitted to food restriction, with access to fresh water, already exposed to sun and shade. In the following six days alfalfa hay and concentrate were provided to the animals (3%BW). Parameters assessed were respiratory rate (FR), rectal temperature (TR), ß-hydroxybutyrate, urinary pH, dry matter intake (IMS) and climate data (air temperature, humidity, and temperature-humidity index - ITU). The parameter that most differed between groups was FR. All animals presented negative energy balance (BHB>0.8mmol/L; pH<7,0). Ewe lambs submitted to food restriction during periods of high temperature and humidity have lower respiratory rate and intern temperature, independently of being exposed to sun or shade. However, when food was offered animals exposed to sun had lower dry matter intake.(AU)

The occurrence of diseases and their relationship with passive immune transfer in Holstein dairy calves submitted to individual management in southern Brazil / Ocorrência de doenças e sua relação com a transferência de imunidade passiva em bezerras Holandês criadas em sistema individual no sul do Brasil

Calves are extremely dependent on colostrum intake for the acquisition of passive immunity. This study aimed to determine the occurrence of diarrhea and respiratory diseases and the impact of Failure of Passive Immune Transfer (FPIT) on the health and zootechnical performance of Holstein dairy calves in individual management. This study has been carried out in five commercial farms in Rio Grande do Sul State, Brazil, from March 2017 to January 2018. In this study, 131 calves were followed from birth to 60 days of age. Total Plasmatic Protein (TPP) has been performed to determine passive immune transfer quality in 53 calves (53/131). A daily clinical follow-up has been accomplished aiming at diagnosing diseases and their incidences, and zootechnical measures such as withers height, width of the croup and weight have been evaluated. FPIT rate was 32.07%, diarrhea occurrence and respiratory diseases were 77.9% and 49.6%, respectively. FPIT increased the chances of calves presenting diarrhea and developing respiratory diseases, but no differences on zootechnical performance were found. The frequency of FPIT is still high and is a factor that corroborated the increased risk for diarrhea and respiratory disease but did not influence the performance of calves in the preweaning phase.(AU)

Bezerras são extremamente dependentes da ingestão de colostro para adquirir imunidade passiva. Este estudo teve o objetivo de determinar os índices de ocorrência de diarreia e de doença respiratória, assim como o impacto da falha na transferência de imunidade passiva (FTIP) no desenvolvimento de doenças e no desempenho zootécnico de bezerras Holandês criadas em sistema individual. O estudo foi desenvolvido em cinco propriedades comerciais no Rio Grande do Sul, Brasil, entre março de 2017 e janeiro de 2018. Assim, 131 bezerras foram acompanhadas, do nascimento aos 60 dias de idade. Em 53 animais, foi realizada avaliação de proteínas plasmáticas totais para determinar a qualidade na transferência de imunidade passiva. Acompanhamento clínico diário foi realizado, a fim de diagnosticar doenças e suas incidências, assim como avaliações zootécnicas, como altura de cernelha, largura de garupa, perímetro torácico e peso. O percentual de FTIP foi 32,07%, a ocorrência de diarreias e de doenças respiratórias foi, respectivamente, 77,9% e 49,6%. A FTIP aumentou as chances de as bezerras apresentarem diarreia e doenças respiratórias, mas não alterou o desempenho zootécnico. Conclui-se que a frequência na FTIP ainda é elevada, fator que corroborou o aumento do risco para as diarreias e doença respiratória. Apesar disso, a FTIP não influenciou no desenvolvimento das bezerras na fase de aleitamento.(AU)

Effects of timing of artificial insemination and treatment of semen with a Slo3 potassium channel blocker on fertility of dairy heifers subjected to the 5-day CIDR-Synch protocol.

Two experiments were conducted to evaluate the effects of the timing of artificial insemination (AI) and incorporation of the Slo3 K+ channel blocker 4-(4-chlorophenyl)butyl-diethyl-heptylammonium to semen extender (CSE) on pregnancy per AI (P/AI) and pregnancy loss in dairy heifers. In experiment 1, Holstein heifers were subjected to the 5-d CIDR-Synch protocol: d -8 GnRH and controlled internal drug-release device (CIDR); d -3 PGF2α and CIDR removal; d -2 PGF2α; d 0 GnRH) and assigned randomly to receive timed AI with control semen on d 0 (72-CON; n = 104), control semen on d -1 (48-CON; n = 100), or CSE-treated semen on d -1 (48-CSE; n = 98). Heifers were fitted with collar-mounted automated estrus detection devices to monitor physical activity and rumination. In experiment 2, Holstein heifers were subjected to the 5-d CIDR-Synch protocol and received a mount detection patch at the first PGF2α injection. Heifers detected in estrus before d 0 were inseminated on the same day, whereas those not detected in estrus received the second GnRH injection and timed AI on d 0. Heifers were assigned randomly to receive AI with control (AI-CON; n = 148) or CSE-treated semen (AI-CSE; n = 110). Four bulls with proven fertility were used in both experiments, and ejaculates from each sire were divided and processed as CON or CSE. Pregnancy was diagnosed by transrectal ultrasonography at 29 and 54 d after AI. Data were analyzed by logistic regression, and statistical models included the fixed effects of treatment and enrollment week. In experiment 1, orthogonal contrasts were built to assess the effects of day of AI (72-CON vs. 48-CON + 48-CSE) and treatment of semen with CSE (48-CON vs. 48-CSE). Pregnancy per AI on d 29 (72-CON = 60.8, 48-CON = 35.2, 48-CSE = 39.8%) and d 54 (72-CON = 58.2, 48-CON = 31.6, 48-CSE = 36.2%) was greater for heifers inseminated on d 0 compared with d -1. However, no effect of semen extender on P/AI was observed in heifers inseminated on d -1. In experiment 2, P/AI tended to be greater for AI-CSE than for AI-CON on d 29 (58.6 vs. 47.3%) and d 54 after AI (55.6 vs. 43.7%). Advancing AI by 24 h decreased the likelihood of pregnancy, and use of CSE was unable to overcome the expected asynchrony between insemination and ovulation. Nevertheless, incorporation of CSE in semen processing tended to improve P/AI when heifers received AI upon detected estrus or timed AI concurrently with the final GnRH of the 5-d CIDR-Synch protocol.

Vitamin D supplementation improves the metabolic syndrome risk profile in postmenopausal women.

Objective: This study aimed to evaluate the effect of isolated vitamin D (VD) supplementation on the metabolic syndrome (MetS) risk profile in postmenopausal women.Methods: In this double-blind, placebo-controlled trial, 160 postmenopausal women aged 50-65 years were randomized into two groups: VD group, supplementation with 1000 IU vitamin D3/day (n = 80); or placebo group (n = 80). The intervention time was 9 months, and the women were assessed at baseline and endpoint. Clinical and anthropometric data were collected. Biochemical parameters, including total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, glucose, and insulin, were measured. The plasma concentration of 25-hydroxyvitamin D (25(OH)D) was measured by high-performance liquid chromatography.Results: After 9 months, there was a significant increase in the 25(OH)D levels for VD group (+45.4%, p < 0.001), and a decrease (-18.5%, p = 0.049) in the placebo group. In the VD group, a significant reduction was observed in triglycerides (-12.2%, p = 0.001), insulin (-13.7%, p = 0.008), and the homeostasis model assessment of insulin resistance (-17.9%, p = 0.007). In the placebo group, there was an increase in glucose (+6.2%, p = 0.009). Analysis of the risk adjusted for age, time since menopause, and body mass index showed that women supplemented with VD had a lower risk of MetS (odds ratio [OR] 0.42; 95% confidence interval [CI] 0.21-0.83), hypertriglyceridemia (OR 0.43; 95% CI 0.22-0.85), and hyperglycemia (OR 0.23; 95% CI 0.10-0.52) compared to the placebo group (p < 0.05).Conclusions: In postmenopausal women with VD deficiency, isolated supplementation with 1000 IU vitamin D3 for 9 months was associated with a reduction in the MetS risk profile. Women undergoing VD supplementation had a lower risk of MetS, hypertriglyceridemia, and hyperglycemia.

Altered rumen fermentation patterns in lactating dairy cows supplemented with phytochemicals improve milk production and efficiency.

Tannins and other phytochemicals are known to improve RUP in the diet by binding protein and then limiting ruminal degradation, which may improve milk yield and milk protein synthesis. The objective of this study was to evaluate the effects of dietary phytochemicals (tannins and Capsicum species) as rumen modifiers on production parameters and milk efficiency in dairy cows. Twenty-four multiparous Holstein cows (96 ± 16 d in milk; mean ± standard deviation) were used in a replicated 3 × 3 Latin square design balanced to measure carryover effects. Cows were blocked according to days in milk, milk production, and body weight and randomly assigned to 1 of 3 groups (n = 8/group). Each group was assigned to a unique treatment sequence across the 3 periods in the Latin square. The experiment consisted of a 14-d covariate period and three 30-d treatment periods. Cows received a basal diet supplemented with soybean meal pellets (SB) as the control diet, phytochemicals (RUM; Rumiviv, CCPA, Janzé, France) pelleted with soybean meal, or expeller soybean meal (ESBM; SoyPlus, West Central Soy, Ralston, IA). Milk production and dry matter intake during the last 4 d of each period were used for statistical analysis. Blood and rumen fluid samples were collected on d 27 of each period. Rumen fluid was analyzed for ammonia N and volatile fatty acids as well as ruminal bacteria via quantitative PCR amplification of 16S ribosomal DNA genes. Greater milk yield (37.9 vs. 36 kg/d), energy-corrected milk (39.7 vs 37.1 kg/d), and protein yield (1.15 vs. 1.08 kg/d) were observed in RUM compared with SB, but these parameters were similar between RUM and ESBM. Concentrations of total volatile fatty acids (118.1 vs. 101.5 mM) were greater in RUM in comparison to SB and ESBM diets. Cows fed RUM had greater ß-hydroxybutyrate (0.49 vs. 0.42 mmol/L) than SB and ESBM. Selenomonas ruminantium, Succinimonas amylolytica, and Streptococcus bovis in rumen fluid were lower in RUM fed cows in comparison to SB and ESBM. Increased total volatile fatty acids and lower ruminal abundance of bacteria associated with low feed efficiency in RUM cows can partially explain the improvements observed in milk yield and milk efficiency. Overall, these data suggest that feeding a combination of tannin mixture and Capsicum can significantly affect rumen fermentation characteristics via partial manipulation of rumen microbiota, and these effects were reflected in improved milk production and efficiency.

Two Rare Complications in One Patient: Acquired von Willebrand Syndrome Associated with Intracranial Plasmacytoma.

Here, we describe a rare case of acquired von Willebrand syndrome (VWS) associated with intracranial plasmacytoma. The literature includes reports of a few cases of plasmacytoma with central nervous involvement, but none of them with acquired VWS. Diagnosis was made based on a stereotaxic intracerebral biopsy. During this biopsy, a ventriculoperitoneal shunt was established, which was complicated with abnormal bleeding. Subsequent hemostasis assessment related to hemopathy revealed acquired von Willebrand disease. The patient received induction therapy with bortezomib, thalidomide, and dexamethasone (VTD), followed by high-dose melphalan chemotherapy and autologous stem cell transplantation, and then VTD consolidation, and finally maintenance with lenalidomide. Our patient currently remains in very good partial response without neurological symptoms after 4 months of maintenance. The patient is free of progression 14 months after their original presentation.

Fatty acid composition of vegetable oil blend and in vitro effects of pharmacotherapeutical skin care applications.

Vegetable oils have been used for a plethora of health benefits by their incorporation in foods, cosmetics, and pharmaceutical products, especially those intended for skin care. This study aimed to investigate the cutaneous benefits of a vegetable oil blend (VOB) formulation and its fatty acid composition. The anti-inflammatory activity was studied in macrophages of RAW 264.7 cells by investigating the release of nitric oxide (NO), superoxide anion generation (O2-), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). ABTS cation radical scavenging capacity assay, ferric reducing antioxidant potential (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and NO free radical scavenging assays were used to evaluate the antioxidant activity. VOB was tested for its ability to stimulate fibroblast proliferation and migration using the scratch assay, and antibacterial activity by the microdilution test. The fatty acid profile of a freshly prepared VOB formulation was determined by gas chromatography before and after accelerated stability testing. Chemical composition of VOB revealed the presence of oleic acid (C18:1n-9; 63.3%), linoleic acid (C18:2n-6; 4.7%), and linolenic acid (C18:3n-6; 5.1%) as major mono- and polyunsaturated fatty acids. No changes in the organoleptic characteristics and fatty acid composition were observed after the accelerated stability test. VOB 100 µg/mL reduced the healing time by increasing the total number of cells in the wounded area by 43.0±5.1% compared to the negative control group. VOB also suppressed the pro-inflammatory TNF-α and IL-6 cytokines, and NO and O2- production in lipopolysaccharide-stimulated macrophage cells. In conclusion, the VOB formulation contributed to the improvement of current therapeutic strategies for cutaneous applications in skin care.

MODELING STUDIES ON DICENTRICS INDUCTION AFTER SUB-MICROMETER FOCUSED ION BEAM GRID IRRADIATION.

The biophysical simulation tool PARTRAC contains modules for DNA damage response representing non-homologous end joining of DNA double-strand breaks (DSB) and the formation of chromosomal aberrations. Individual DNA ends from the induced DSB are followed regarding both their enzymatic processing and spatial mobility, as is needed for chromosome aberrations to arise via ligating broken ends from different chromosomes. In particular, by tracking the genomic locations of the ligated fragments and the positions of centromeres, the induction of dicentrics can be modeled. In recent experiments, the impact of spatial clustering of DNA damage on dicentric yields has been assessed in AL human-hamster hybrid cells: Defined numbers of 20 MeV protons (linear energy transfer, LET 2.6 keV/µm), 45 MeV Li ions (60 keV/µm) and 55 MeV C ions (310 keV/µm) focused to sub-µm spot sizes were applied with the ion microbeam SNAKE in diverse grid modes, keeping the absorbed dose constant. The impact of the µm-scaled spatial distribution of DSB (focusing effect) has thus been separated from nm-scaled DSB complexity (LET effect). The data provide a unique benchmark for the model calculations. Model and parameter refinements are described that enabled the simulations to largely reproduce both the LET-dependence and the focusing effect as well as the usual biphasic rejoining kinetics. The predictive power of the refined model has been benchmarked against dicentric yields for photon irradiation.

MODELING DNA DAMAGE BY PHOTONS AND LIGHT IONS OVER ENERGY RANGES USED IN MEDICAL APPLICATIONS.

Comprehensive track structure-based simulations of DNA damage induced in human cells by photons (5 keV-1.3 MeV) and light ions (0.25-512 MeV/u) were performed with PARTRAC. DNA strand breaks, double-strand breaks and their clustering were scored. Effective LET values were established for photons that provide LET-dependent damage yields in agreement with the data for ions. The resulting database captures the variations of biological effectiveness with radiation quality. In particular, it can help compare the effectiveness of conventional radiotherapy using photon beams with techniques relying on proton or ion beams.

Hematological and biochemical parameters of dairy calves submitted to pegbovigrastim administration.

This study was designed to evaluate the response of hematological and biochemical parameters submitted to pegbovigrastim administration and postchallenge with lipopolysaccharide (LPS). In experiment 1, 20 newborn Holstein calves were divided into 2 groups: the Imrestor (Elanco Saúde Animal, São Paulo, Brazil) group (IMR, n = 10), which received a 25 µg/kg of body weight (BW) subcutaneous administration of pegbovigrastim, and the control group (CTR, n = 10), which received a subcutaneous administration of 0.9% saline solution. Blood samples were collected on d 0, 10, 12, and 14 relative to birth to analyze the biochemical and hematological parameters. Moreover, growth measurements were taken on d 0, 7, 14, 21, and 60 relative to birth. The number of total leukocytes in the IMR group increased on d 12 and 14 in comparison to the CTR group, as well as the counts of segmented neutrophils, band cells, and monocytes. No differences were observed in the other hematological, biochemical, and growth parameters. In experiment 2, 20 Holstein calves from 30 to 60 d old were divided into 4 groups: group 1 (LPS, n = 5) received a 0.25 µg/kg of BW single intravenous dose of Escherichia coli LPS at d 0; group 2 (IMR, n = 5) received a 25 µg/kg of BW subcutaneous dose of pegbovigrastim at d 1; group 3 (IMR + LPS, n = 5) received a 0.25 µg/kg of BW intravenous LPS dose at d 0 and a 25 µg/kg of BW subcutaneous dose of pegbovigrastim at d 1; and group 4 (CTR, n = 5) received an intravenous dose of 0.9% sodium chloride at d 0 and a subcutaneous dose of 0.9% sodium chloride at d 1. For the analysis of biochemical and hematological parameters, blood samples were collected on d -1, 0, 1, 2, 3, 4, 8, 14, and 21 relative to LPS administration. An increase in the number of total leukocytes was observed in the IMR, IMR + LPS, and LPS groups, and the IMR group remained as the highest from d 2 to 21. The levels of paraoxonase 1 were higher in the IMR group compared with all the others. The administration of pegbovigrastim in the dairy calves increased the number of circulating leukocytes, especially neutrophils, with an increase in paraoxonase 1, without altering the metabolites for the hepatic function.

Fatty acid composition of vegetable oil blend and in vitro effects of pharmacotherapeutical skin care applications

Vegetable oils have been used for a plethora of health benefits by their incorporation in foods, cosmetics, and pharmaceutical products, especially those intended for skin care. This study aimed to investigate the cutaneous benefits of a vegetable oil blend (VOB) formulation and its fatty acid composition. The anti-inflammatory activity was studied in macrophages of RAW 264.7 cells by investigating the release of nitric oxide (NO), superoxide anion generation (O2-), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). ABTS cation radical scavenging capacity assay, ferric reducing antioxidant potential (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and NO free radical scavenging assays were used to evaluate the antioxidant activity. VOB was tested for its ability to stimulate fibroblast proliferation and migration using the scratch assay, and antibacterial activity by the microdilution test. The fatty acid profile of a freshly prepared VOB formulation was determined by gas chromatography before and after accelerated stability testing. Chemical composition of VOB revealed the presence of oleic acid (C18:1n-9; 63.3%), linoleic acid (C18:2n-6; 4.7%), and linolenic acid (C18:3n-6; 5.1%) as major mono- and polyunsaturated fatty acids. No changes in the organoleptic characteristics and fatty acid composition were observed after the accelerated stability test. VOB 100 µg/mL reduced the healing time by increasing the total number of cells in the wounded area by 43.0±5.1% compared to the negative control group. VOB also suppressed the pro-inflammatory TNF-α and IL-6 cytokines, and NO and O2- production in lipopolysaccharide-stimulated macrophage cells. In conclusion, the VOB formulation contributed to the improvement of current therapeutic strategies for cutaneous applications in skin care.

Effect of isolated vitamin D supplementation on bone turnover markers in younger postmenopausal women: a randomized, double-blind, placebo-controlled trial.

Vitamin D (VD) plays an important role in bone mineralization. The present study investigates the effect of VD supplementation alone on bone turnover markers in younger postmenopausal women. It has been shown that VD supplementation in postmenopausal women with hypovitaminosis D is associated with a reduction in bone turnover markers. PURPOSE: The purpose of this study is to evaluate the effect of VD supplementation alone on bone turnover markers in younger postmenopausal women. METHODS: In this double-blind, placebo-controlled trial, 160 women were randomized into the VD group (supplementation with 1000 IU of vitamin D3/day, orally; n = 80) or placebo group (n = 80). Women aged 50-65 years with amenorrhea ≥ 12 months and normal bone mineral density were included. The intervention lasted 9 months, and the participants were assessed at the beginning and end of treatment. Serum levels of total calcium, parathormone (PTH), alkaline phosphatase (AP), and 24-h urine calcium were determined. Serum C-terminal telopeptide of type I collagen (s-CTX) and procollagen type 1 N-terminal propeptide (P1NP) were measured by immunoassay as markers of bone resorption and formation, respectively. Plasma 25-hydroxyvitamin-D [25(OH)D] concentrations were measured by HPLC. Intention-to-treat analysis was performed using ANOVA, Student's t test, Tukey's test, and gamma distribution. RESULTS: Over the period of 9 months, 25(OH)D concentrations increased from 15.0 ± 7.5 to 27.5 ± 10.4 ng/mL (+ 45.4%) in the VD group and decreased from 16.9 ± 6.7 to 13.8 ± 6.0 ng/mL (- 18.5%) in the placebo group (p < 0.001). There was a decrease (- 21.3%) of PTH levels in the VD group with a significant difference between groups at the end of the study (p < 0.001). No significant differences were observed in the other laboratory parameters (total calcium, AP, and calciuria) in either group (p > 0.05). A comparison of bone turnover markers showed a significant reduction in of s-CTX (- 24.2%, p < .0001) and P1NP (- 13.4%, p = 0.003) levels in the VD group. No significant variations in bone turnover markers were observed in the placebo group (s-CTX, - 6.9%, p = 0.092 and P1NP, - 0.6%, p = 0.918). CONCLUSION: In younger postmenopausal women with VD deficiency, isolated supplementation with 1000 IU of vitamin D3 for 9 months is associated with a reduction in bone turnover markers. However, any between-group differences was not observed in bone turnover markers.

Effect of porcine somatotropin on metabolism, testicular size and sperm characteristics in young boars / Efeito da somatotrofina suína sobre o metabolismo, o tamanho testicular e a qualidade espermática de cachaços jovens

The aim of this study was to evaluate the effect of pST injections on metabolism, testicular size, and sperm characteristics in young boars. Sixty 22-day old piglets were divided into two groups: pST (n=30) and Control (n=30). The pST group was submitted to pST injections (90µg/kg body weight) every three days up to 330 days of age. Blood collections were performed weekly. Testicular weight was measures at 22, 82, 142, 202 and 365 days of age. Libido and fresh semen characteristics were evaluated between 150 and 210 days of age. Semen characteristics were also evaluated during a 72h storage period (15ºC). Testosterone, albumin, and phosphorus blood concentrations were higher in the pST group (P<0.05). The pST group had a higher IGF-I concentration in seminal plasma (P=0.05) and higher testicular weight (P<0.001) compared to the Control group. The pST group had higher ejaculate volume (P<0.001), total sperm count (P=0.047) and number of inseminating doses/ejaculate (P=0.047). During the 72h storage period, the pST group had a lower number of morphological alterations (P<0.001) compared to the Control group. In sum, pST injection in young boars increased testosterone concentration, testicular size, and sperm quality.(AU)

O objetivo deste estudo foi determinar o efeito da administração de pST sobre o metabolismo, o tamanho testicular e a qualidade espermática de cachaços jovens. Foram usados leitões com 22 dias de idade, divididos em dois grupos: pST (n=30) e controle (n=30). O grupo pST foi submetido a injeções de pST (90µg/kg de peso vivo) a cada três dias até 330 dias de idade. Peso testicular foi avaliado aos 22, 82, 142, 202 e 365 dias de idade. Libido e qualidade do sêmen fresco foram avaliados entre 150 e 210 dias de idade. Qualidade espermática foi avaliada durante refrigeração (15ºC) por um período de 72 horas. Concentrações sanguíneas de testosterona, albumina e fósforo foram maiores no grupo pST (P<0,05). O grupo pST apresentou maior concentração de IGF-I no plasma seminal (P=0,05) e maior peso testicular, quando comparado ao grupo controle (P<0,001). O grupo pST apresentou maior volume espermático (P<0,001), concentração espermática (P=0,047) e número de doses espermáticas por ejaculado (P=0,047). Durante o período de 72 horas de refrigeração, o grupo pST teve menor número de patologias espermáticas (P<0,001). Assim, conclui-se que a administração de pST aumenta a concentração sanguínea de testosterona, o tamanho testicular e a qualidade espermática de cachaços jovens.(AU)

AT THE PHYSICS-BIOLOGY INTERFACE: THE NEUTRON AFFAIR.

We present predictions of neutron relative biological effectiveness (RBE) for cell irradiations with neutron beams at PTB-Braunschweig. A neutron RBE model is adopted to evaluate initial DNA damage induction given the neutron-induced charged particle field. RBE values are predicted for cell exposures to quasi-monoenergetic beams (0.56 MeV, 1.2 MeV) and to a broad energy distribution neutron field with dose-averaged energy of 5.75 MeV. Results are compared to what obtained with our RBE predictions for neutrons at similar energies, when a 30-cm sphere is irradiated in an isotropic neutron field. RBE values for experimental conditions are higher for the lowest neutron energies, because, as expected, target geometry determines the weight of the low-effectiveness photon component of the neutron dose. These results highlight the importance of characterizing neutron fields in terms of physical interactions, to fully understand neutron-induced biological effects, contributing to risk estimation and to the improvement of radiation protection standards.