Assessing the Role of Asthma on the Relationship between Neurodevelopmental Disabilities and Adverse Birth Outcomes.

BACKGROUND: Investigating asthma as an effect modifier between adverse birth outcomes and neurodevelopmental disabilities (NDDs) across different races is crucial for tailored interventions and understanding variable susceptibility among diverse populations. METHODS: Data were collected through the National Survey of Children's Health. This cross-sectional study included 131,774 children aged 0 to 17 years. Study exposures comprised adverse birth outcomes including preterm birth and low birth weight. Weighted prevalence estimates and odds ratios with 95% confidence intervals (CIs) among children with and without adverse birth outcomes were calculated for NDDs including attention-deficit/hyperactivity disorder, autism spectrum disorder, cerebral palsy, seizure, and several others including behavior problems. Adjusted odds ratios were stratified by asthma status and separate interactions were assessed for each outcome. RESULTS: Of 131,774 participants, 10,227 were born low birth weight (9.12%; 95% CI: 8.77% to 9.49%), 14,058 were born preterm (11.35%; 95% CI: 10.94% to 11.76%), and 16,166 participants had asthma (11.97%; 95% CI: 11.58% to 12.37%). There were 68,100 males (51.11%), 63,674 females (48.89%), 102,061 non-Hispanic Whites (NHW) (66.92%), 8,672 non-Hispanic Blacks (NHB) (13.97%), and 21,041 participants (19.11%) categorized as other. NHB children with adverse birth outcomes had higher prevalence of several NDDs compared to NHW children. CONCLUSIONS: Asthma was not shown to be an effect modifier of the association between adverse birth outcomes and NDDs. Nevertheless, these results suggest that NDDs are more prevalent within US children with adverse birth outcomes, with higher rates among NHB compared to NHW children. These findings support screening for NDDs in pediatric health care settings among patients with adverse birth outcomes, particularly among those from ethnic minority backgrounds.

Estimating the likelihood of epilepsy from clinically noncontributory electroencephalograms using computational analysis: A retrospective, multisite case-control study.

OBJECTIVE: This study was undertaken to validate a set of candidate biomarkers of seizure susceptibility in a retrospective, multisite case-control study, and to determine the robustness of these biomarkers derived from routinely collected electroencephalography (EEG) within a large cohort (both epilepsy and common alternative conditions such as nonepileptic attack disorder). METHODS: The database consisted of 814 EEG recordings from 648 subjects, collected from eight National Health Service sites across the UK. Clinically noncontributory EEG recordings were identified by an experienced clinical scientist (N = 281; 152 alternative conditions, 129 epilepsy). Eight computational markers (spectral [n = 2], network-based [n = 4], and model-based [n = 2]) were calculated within each recording. Ensemble-based classifiers were developed using a two-tier cross-validation approach. We used standard regression methods to assess whether potential confounding variables (e.g., age, gender, treatment status, comorbidity) impacted model performance. RESULTS: We found levels of balanced accuracy of 68% across the cohort with clinically noncontributory normal EEGs (sensitivity =61%, specificity =75%, positive predictive value =55%, negative predictive value =79%, diagnostic odds ratio =4.64, area under receiver operated characteristics curve =.72). Group level analysis found no evidence suggesting any of the potential confounding variables significantly impacted the overall performance. SIGNIFICANCE: These results provide evidence that the set of biomarkers could provide additional value to clinical decision-making, providing the foundation for a decision support tool that could reduce diagnostic delay and misdiagnosis rates. Future work should therefore assess the change in diagnostic yield and time to diagnosis when utilizing these biomarkers in carefully designed prospective studies.

Orthogonal-view microscope for the biomechanics investigations of aquatic organisms.

Microscopes are essential for the biomechanical and hydrodynamical investigation of small aquatic organisms. We report a prototype of a do-it-yourself microscope that enables the visualization of organisms from two orthogonal imaging planes - top and side views. Compared to conventional imaging systems, this approach provides a comprehensive visualization strategy of organisms, which could have complex shapes and morphologies. The microscope was constructed by combining custom 3D-printed parts and off-the-shelf components. The system is designed for modularity and reconfigurability. Open-source design files and build instructions are provided in this report. Additionally, proof-of-use experiments (particularly with Hydra) and other organisms that combine the imaging with an analysis pipeline were demonstrated to highlight the system's utility. Beyond the applications demonstrated, the system can be used or modified for various imaging applications.

Enriched mesoporous bioactive glass scaffolds as bone substitutes in critical diaphyseal bone defects in rabbits.

In the field of orthopedic surgery, there is an increasing need for the development of bone replacement materials for the treatment of bone defects. One of the main focuses of biomaterials engineering are advanced bioceramics like mesoporous bioactive glasses (MBG´s). The present study compared the new bone formation after 12 weeks of implantation of MBG scaffolds with composition 82,5SiO2-10CaO-5P2O5-x 2.5SrO alone (MBGA), enriched with osteostatin, an osteoinductive peptide, (MBGO) or enriched with bone marrow aspirate (MBGB) in a long bone critical defect in radius bone of adult New Zealand rabbits. New bone formation from the MBG scaffold groups was compared to the gold standard defect filled with iliac crest autograft and to the unfilled defect. Radiographic follow-up was performed at 2, 6, and 12 weeks, and microCT and histologic examination were performed at 12 weeks. X-Ray study showed the highest bone formation scores in the group with the defect filled with autograft, followed by the MBGB group, in addition, the microCT study showed that bone within defect scores (BV/TV) were higher in the MBGO group. This difference could be explained by the higher density of newly formed bone in the osteostatin enriched MBG scaffold group. Therefore, MBG scaffold alone and enriched with osteostatin or bone marrow aspirate increase bone formation compared to defect unfilled, being higher in the osteostatin group. The present results showed the potential to treat critical bone defects by combining MBGs with osteogenic peptides such as osteostatin, with good prospects for translation into clinical practice. STATEMENT OF SIGNIFICANCE: Treatment of bone defects without the capacity for self-repair is a global problem in the field of Orthopedic Surgery, as evidenced by the fact that in the U.S alone it affects approximately 100,000 patients per year. The gold standard of treatment in these cases is the autograft, but its use has limitations both in the amount of graft to be obtained and in the morbidity produced in the donor site. In the field of materials engineering, there is a growing interest in the development of a bone substitute equivalent. Mesoporous bioactive glass (MBG´s) scaffolds with three-dimensional architecture have shown great potential for use as a bone substitutes. The osteostatin-enriched Sr-MBG used in this long bone defect in rabbit radius bone in vivo study showed an increase in bone formation close to autograft, which makes us think that it may be an option to consider as bone substitute.

Near-infrared hyperspectral imaging and robust statistics for in vivo non-melanoma skin cancer and actinic keratosis characterisation.

One of the most common forms of cancer in fair skinned populations is Non-Melanoma Skin Cancer (NMSC), which primarily consists of Basal Cell Carcinoma (BCC), and cutaneous Squamous Cell Carcinoma (SCC). Detecting NMSC early can significantly improve treatment outcomes and reduce medical costs. Similarly, Actinic Keratosis (AK) is a common skin condition that, if left untreated, can develop into more serious conditions, such as SCC. Hyperspectral imagery is at the forefront of research to develop non-invasive techniques for the study and characterisation of skin lesions. This study aims to investigate the potential of near-infrared hyperspectral imagery in the study and identification of BCC, SCC and AK samples in comparison with healthy skin. Here we use a pushbroom hyperspectral camera with a spectral range of ≈ 900 to 1600 nm for the study of these lesions. For this purpose, an ad hoc platform was developed to facilitate image acquisition. This study employed robust statistical methods for the identification of an optimal spectral window where the different samples could be differentiated. To examine these datasets, we first tested for the homogeneity of sample distributions. Depending on these results, either traditional or robust descriptive metrics were used. This was then followed by tests concerning the homoscedasticity, and finally multivariate comparisons of sample variance. The analysis revealed that the spectral regions between 900.66-1085.38 nm, 1109.06-1208.53 nm, 1236.95-1322.21 nm, and 1383.79-1454.83 nm showed the highest differences in this regard, with <1% probability of these observations being a Type I statistical error. Our findings demonstrate that hyperspectral imagery in the near-infrared spectrum is a valuable tool for analyzing, diagnosing, and evaluating non-melanoma skin lesions, contributing significantly to skin cancer research.

Recent Findings on Therapeutic Cancer Vaccines: An Updated Review.

Cancer remains one of the global leading causes of death and various vaccines have been developed over the years against it, including cell-based, nucleic acid-based, and viral-based cancer vaccines. Although many vaccines have been effective in in vivo and clinical studies and some have been FDA-approved, there are major limitations to overcome: (1) developing one universal vaccine for a specific cancer is difficult, as tumors with different antigens are different for different individuals, (2) the tumor antigens may be similar to the body's own antigens, and (3) there is the possibility of cancer recurrence. Therefore, developing personalized cancer vaccines with the ability to distinguish between the tumor and the body's antigens is indispensable. This paper provides a comprehensive review of different types of cancer vaccines and highlights important factors necessary for developing efficient cancer vaccines. Moreover, the application of other technologies in cancer therapy is discussed. Finally, several insights and conclusions are presented, such as the possibility of using cold plasma and cancer stem cells in developing future cancer vaccines, to tackle the major limitations in the cancer vaccine developmental process.

Advances in the Production of Sustainable Bacterial Nanocellulose from Banana Leaves.

Interest in bacterial nanocellulose (BNC) has grown due to its purity, mechanical properties, and biological compatibility. To address the need for alternative carbon sources in the industrial production of BNC, this study focuses on banana leaves, discarded during harvesting, as a valuable source. Banana midrib juice, rich in nutrients and reducing sugars, is identified as a potential carbon source. An optimal culture medium was designed using a simplex-centroid mixing design and evaluated in a 10 L bioreactor. Techniques such as Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), and thermogravimetric analysis (TGA) were used to characterize the structural, thermal, and morphological properties of BNC. Banana midrib juice exhibited specific properties, such as pH (5.64), reducing sugars (15.97 g/L), Trolox (45.07 µM), °Brix (4.00), and antioxidant activity (71% DPPH). The model achieved a 99.97% R-adjusted yield of 6.82 g BNC/L. Physicochemical analyses revealed distinctive attributes associated with BNC. This approach optimizes BNC production and emphasizes the banana midrib as a circular solution for BNC production, promoting sustainability in banana farming and contributing to the sustainable development goals.

Force Production and Electromyographic Activity during Different Flywheel Deadlift Exercises.

This study aimed to characterize and compare force production and muscle activity during four flywheel deadlift exercises (bilateral [Bi] vs. unilateral [Uni]) with different loading conditions (vertical [Ver] vs. horizontal [Hor]). Twenty-three team-sport athletes underwent assessments for exercise kinetics (hand-grip force), along with surface electromyography (sEMG) of the proximal (BFProx) and medial biceps femoris (BFMed), semitendinosus (ST), and gluteus medius (GM). Mean and peak force were highest (p < 0.001) in Bi + Ver compared with Bi + Hor, Uni + Ver, and Uni + Hor. Although no significant differences were observed between Bi + Hor and Uni + Ver, both variants showed higher (p < 0.001) average force and peak eccentric force when compared with Uni + Hor. The presence of eccentric overload was only observed in the vertically loaded variants. Bi + Ver and Uni + Ver showed higher (p < 0.05) sEMG levels in BFProx and BFMed compared with the Uni + Hor variant. In addition, Uni + Ver registered the largest GM and ST sEMG values. In conclusion, the vertical variants of the flywheel deadlift exercise led to higher muscle force production and sEMG compared with their horizontal counterparts. Both Bi + Ver and Uni + Ver may be effective in promoting an increase in hamstring muscles activity and muscle force at long muscle length, while the Uni + Ver variant may be more effective in promoting GM and ST involvement.

Assessing Antigen-Specific T Cell Responses Through IFN-γ Enzyme-Linked Immune Absorbent Spot (ELISpot).

T cells are instrumental in protecting the host against invading pathogens and the development of cancer. To do so, they produce effector molecules such as granzymes, interleukins, interferons, and perforin. For the development and immunomonitoring of therapeutic applications such as cell-based therapies and vaccines, assessing T cell effector function is paramount. This can be achieved through various methods, such as 51Cr release assays, flow cytometry, and enzyme-linked immune absorbent spot (ELISpot) assays. For T cell ELISpots, plates are coated with antibodies directed against the effector molecule of interest (e.g., IFN-g). Subsequently, peripheral blood mononuclear cells (PBMCs) or isolated T cells are cultured on the plate together with stimuli of choice, and the production of effector molecules is visualized via labeled detection antibodies. For clinical studies, ELISpot is currently the gold standard to determine antigen-specific T cell frequencies. In contrast to 51Cr release assays, ELISpot allows for the exact enumeration of responding T cells, and compared to flow cytometry, ELISpot is more cost-effective and high throughput. Here, we optimize and describe, in a step-by-step fashion, how to perform a controlled IFN-γ ELISpot experiment to determine the frequency of responding or antigen-specific T cells in healthy human volunteers. Of note, this protocol can also be employed to assess the frequency of antigen-specific T cells induced in, e.g., vaccination studies or present in cellular products.

Practical RGB-to-XYZ Color Transformation Matrix Estimation under Different Lighting Conditions for Graffiti Documentation.

Color data are often required for cultural heritage documentation. These data are typically acquired via standard digital cameras since they facilitate a quick and cost-effective way to extract RGB values from photos. However, cameras' absolute sensor responses are device-dependent and thus not colorimetric. One way to still achieve relatively accurate color data is via camera characterization, a procedure which computes a bespoke RGB-to-XYZ matrix to transform camera-dependent RGB values into the device-independent CIE XYZ color space. This article applies and assesses camera characterization techniques in heritage documentation, particularly graffiti photographed in the academic project INDIGO. To this end, this paper presents COOLPI (COlor Operations Library for Processing Images), a novel Python-based toolbox for colorimetric and spectral work, including white-point-preserving camera characterization from photos captured under diverse, real-world lighting conditions. The results highlight the colorimetric accuracy achievable through COOLPI's color-processing pipelines, affirming their suitability for heritage documentation.

Weekly Programming of Hamstring-Related Training Contents in European Professional Soccer.

Hamstring injuries in soccer continue to be a challenge for professionals who work with soccer players daily. Although its origin is multifactorial, the proper management of neuromuscular fatigue during the training microcycle is a very important factor to consider. There are no clear guidelines regarding the weekly distribution of certain exercises that demand the hamstrings. The main objective of this study was to describe the usual training practices of professional European soccer teams. An international observational survey design was applied to some of the strength and conditioning coaches of professional soccer teams. The survey included different neuromuscular demanding exercises for the hamstrings. For each exercise, the strength and conditioning coaches had to respond in relation to their frequency of use and timepoint depending on the day of the weekly microcycle. Although there is no strong consensus in this regard, there does seem to be a trend when applying certain exercises, especially on the days matchday-4 and matchday-3.

Optical and Electrochemical Properties of a Nanostructured ZnO Thin Layer Deposited on a Nanoporous Alumina Structure via Atomic Layer Deposition.

This study explores the optical and electrochemical properties of a ZnO coating layer deposited on a nanoporous alumina structure (NPAS) for potential multifunctional applications. The NPAS, synthesized through an electrochemical anodization process, displays well-defined nanochannels with a high aspect ratio (~3000). The ZnO coating, achieved via atomic layer deposition, enables the tuning of the pore diameter and porosity of the NPAS, thereby influencing both the optical and electrochemical interfacial properties. A comprehensive characterization using photoluminescence, spectroscopy ellipsometry and impedance spectroscopy (with the sample in contact with NaCl solutions) provides insights into optical and electrochemical parameters, including the refractive index, absorption coefficient, and electrolyte-ZnO/NPAS interface processes. This research demonstrates potential for tailoring the optical and interfacial properties of nanoporous structures by selecting appropriate coating materials, thus opening avenues for their utilization in various technological applications.

Role of human Kallistatin in glucose and energy homeostasis in mice.

OBJECTIVE: Kallistatin (KST), also known as SERPIN A4, is a circulating, broadly acting human plasma protein with pleiotropic properties. Clinical studies in humans revealed reduced KST levels in obesity. The exact role of KST in glucose and energy homeostasis in the setting of insulin resistance and type 2 diabetes is currently unknown. METHODS: Kallistatin mRNA expression in human subcutaneous white adipose tissue (sWAT) of 47 people with overweight to obesity of the clinical trial "Comparison of Low Fat and Low Carbohydrate Diets With Respect to Weight Loss and Metabolic Effects (B-SMART)" was measured. Moreover, we studied transgenic mice systemically overexpressing human KST (hKST-TG) and wild type littermate control mice (WT) under normal chow (NCD) and high-fat diet (HFD) conditions. RESULTS: In sWAT of people with overweight to obesity, KST mRNA increased after diet-induced weight loss. On NCD, we did not observe differences between hKST-TG and WT mice. Under HFD conditions, body weight, body fat and liver fat content did not differ between genotypes. Yet, during intraperitoneal glucose tolerance tests (ipGTT) insulin excursions and HOMA-IR were lower in hKST-TG (4.42 ± 0.87 AU, WT vs. 2.20 ± 0.27 AU, hKST-TG, p < 0.05). Hyperinsulinemic euglycemic clamp studies with tracer-labeled glucose infusion confirmed improved insulin sensitivity by higher glucose infusion rates in hKST-TG mice (31.5 ± 1.78 mg/kg/min, hKST-TG vs. 18.1 ± 1.67 mg/kg/min, WT, p < 0.05). Improved insulin sensitivity was driven by reduced hepatic insulin resistance (clamp hepatic glucose output: 7.7 ± 1.9 mg/kg/min, hKST-TG vs 12.2 ± 0.8 mg/kg/min, WT, p < 0.05), providing evidence for direct insulin sensitizing effects of KST for the first time. Insulin sensitivity was differentially affected in skeletal muscle and adipose tissue. Mechanistically, we observed reduced Wnt signaling in the liver but not in skeletal muscle, which may explain the effect. CONCLUSIONS: KST expression increases after weight loss in sWAT from people with obesity. Furthermore, human KST ameliorates diet-induced hepatic insulin resistance in mice, while differentially affecting skeletal muscle and adipose tissue insulin sensitivity. Thus, KST may be an interesting, yet challenging, therapeutic target for patients with obesity and insulin resistance.

An adenosine derivative promotes mitochondrial supercomplexes reorganization and restoration of mitochondria structure and bioenergetics in a diethylnitrosamine-induced hepatocellular carcinoma model.

Hepatocellular carcinoma (HCC) progression is associated with dysfunctional mitochondria and bioenergetics impairment. However, no data about the relationship between mitochondrial supercomplexes (hmwSC) formation and ATP production rates in HCC are available. Our group has developed an adenosine derivative, IFC-305, which improves mitochondrial function, and it has been proposed as a therapeutic candidate for HCC. We aimed to determine the role of IFC-305 on both mitochondrial structure and bioenergetics in a sequential cirrhosis-HCC model in rats. Our results showed that IFC-305 administration decreased the number and size of liver tumors, reduced the expression of tumoral markers, and reestablished the typical architecture of the hepatic parenchyma. The livers of treated rats showed a reduction of mitochondria number, recovery of the mtDNA/nDNA ratio, and mitochondrial length. Also, IFC-305 increased cardiolipin and phosphatidylcholine levels and promoted hmwSC reorganization with changes in the expression levels of hmwSC assembly-related genes. IFC-305 in HCC modified the expression of several genes encoding elements of electron transport chain complexes and increased the ATP levels by recovering the complex I, III, and V activity. We propose that IFC-305 restores the mitochondrial bioenergetics in HCC by normalizing the quantity, morphology, and function of mitochondria, possibly as part of its hepatic restorative effect.

Whole-genome sequencing and comparative genomics reveal candidate genes associated with quality traits in Dioscorea alata.

BACKGROUND: Quality traits are essential determinants of consumer preferences. Dioscorea alata (Greater Yam), is a starchy tuber crop in tropical regions. However, a comprehensive understanding of the genetic basis underlying yam tuber quality remains elusive. To address this knowledge gap, we employed population genomics and candidate gene association approaches to unravel the genetic factors influencing the quality attributes of boiled yam. METHODS AND RESULTS: Comparative genomics analysis of 45 plant species revealed numerous novel genes absent in the existing D. alata gene annotation. This approach, adding 48% more genes, significantly enhanced the functional annotation of three crucial metabolic pathways associated with boiled yam quality traits: pentose and glucuronate interconversions, starch and sucrose metabolism, and flavonoid biosynthesis. In addition, the whole-genome sequencing of 127 genotypes identified 27 genes under selection and 22 genes linked to texture, starch content, and color through a candidate gene association analysis. Notably, five genes involved in starch content and cell wall composition, including 1,3-beta Glucan synthase, ß-amylase, and Pectin methyl esterase, were common to both approaches and their expression levels were assessed by transcriptomic data. CONCLUSIONS: The analysis of the whole-genome of 127 genotypes of D. alata and the study of three specific pathways allowed the identification of important genes for tuber quality. Our findings provide insights into the genetic basis of yam quality traits and will help the enhancement of yam tuber quality through breeding programs.

ASK1/ p38 axis inhibition blocks the release of mitochondrial "danger signals" from hepatocytes and suppresses progression to cirrhosis and liver cancer.

BACKGROUND AND AIMS: Apoptosis Signal-regulating Kinase 1 (ASK1) is activated by various pathological stimuli and induces cell apoptosis through downstream p38 activation. We studied the effect of pharmacological ASK1 inhibition on cirrhosis and its sequelae using comprehensive preclinical in vivo and in vitro systems. APPROACH AND RESULTS: Short-term (4-6 wk) and long-term (24-44 wk) ASK1 inhibition using small molecule GS-444217 was tested in thioacetamide-induced and BALB/c. Mdr2-/- murine models of cirrhosis and HCC, and in vitro using primary hepatocyte cell death assays. Short-term GS-444217 therapy in both models strongly reduced phosphorylated p38, hepatocyte death, and fibrosis by up to 50%. Profibrogenic release of mitochondrial DAMP mitochondrial deoxyribonucleic acid from dying hepatocytes was blocked by ASK1 or p38 inhibition. Long-term (24 wk) therapy in BALBc.Mdr2 - / - model resulted in a moderate 25% reduction in bridging fibrosis, but not in net collagen deposition. Despite this, the development of cirrhosis was effectively prevented, with strongly reduced p21 + hepatocyte staining (by 72%), serum ammonia levels (by 46%), and portal pressure (average 6.07 vs. 8.53 mm Hg in controls). Extended ASK1 inhibition for 44 wk in aged BALB/c. Mdr2-/- mice resulted in markedly reduced tumor number and size by ~50% compared to the control group. CONCLUSIONS: ASK1 inhibition suppresses the profibrogenic release of mitochondrial deoxyribonucleic acid from dying hepatocytes in a p38-dependent manner and protects from liver fibrosis. Long-term ASK1 targeting resulted in diminished net antifibrotic effect, but the progression to liver cirrhosis and cancer in BALBc/ Mdr2- / - mice was effectively inhibited. These data support the clinical evaluation of ASK1 inhibitors in fibrotic liver diseases.

Evaluating the impact of pre-diagnostic use of statins and testosterone replacement therapy on mortality outcomes in older men with hormone-related cancers: Surveillance, Epidemiology, and End Results-Medicare 2007-2015.

BACKGROUND: The link between the pre-diagnostic use of statins and testosterone replacement therapy and their impact on hormone-related cancers, prostate cancer, colorectal cancer, and male breast cancer survival remains a topic of controversy. Further, there is a knowledge gap concerning the joint effects of statins and testosterone replacement therapy on hormone-related cancer survival outcomes. OBJECTIVE: To examine the independent and joint effects of pre-diagnostic use of statins and testosterone replacement therapy on the risk of all-cause and cause-specific mortality among older men diagnosed with hormone-related cancers, including prostate cancer, colorectal cancer, and male breast cancer. METHODS: In 41,707 men (≥65 years) of Surveillance, Epidemiology, and End Results-Medicare 2007-2015, we identified 31,097 prostate cancer, 10,315 colorectal cancer, and 295 male breast cancer cases. Pre-diagnostic prescription of statins and testosterone replacement therapy was ascertained and categorized into four groups (Neither users, statins alone, testosterone replacement therapy alone, and Dual users). Multivariable-adjusted Cox proportional hazards and competing-risks (Fine-Gray subdistribution hazard) models were conducted. RESULTS: No significant associations were found in Cox-proportional hazard models for hormone-related cancers. However, in the Fine-Gray competing risk models among high-grade hormone-related cancers, statins alone had an 11% reduced risk of hormone-related cancer-specific death (hazard ratio: 0.89; 95% confidence interval: 0.81-0.99; p 0.0451). In the prostate cancer cohort with both statistical models, the use of testosterone replacement therapy alone had a 24% lower risk of all-cause death (hazard ratio: 0.76; 95% confidence interval: 0.59-0.97; p 0.0325) and a 57% lower risk of prostate cancer-specific death (hazard ratio: 0.43; 95% confidence interval: 0.24-0.75; p 0.0029). Similar inverse associations were found among aggressive prostate cancer cases with testosterone replacement therapy alone and statins alone. No significant associations were found in the colorectal cancer and male breast cancer sub-groups. CONCLUSION: Pre-diagnostic use of statins and testosterone replacement therapy showed a survival benefit with reduced mortality in high-grade hormone-related cancer patients (only statins) and aggressive prostate cancer patients in both statistical models. Findings of testosterone replacement therapy use in aggressive prostate cancer settings could facilitate clinical trials. Further studies with extended follow-up periods are needed to substantiate these findings.

In vivo behavior in rabbit radius bone defect of scaffolds based on nanocarbonate hydroxyapatite.

Bone defects treatment may require the use of biomaterials that behave as a support and promote bone regeneration. Limitations associated with the use of autografts and allografts make it necessary to design new synthetic bone substitutes. Some of the most promising biomaterials currently under investigation are based on nanocarbonate hydroxyapatite (nCHA). In this study, we studied the bone-inducing capacity of nCHA-based scaffolds alone (SAG) and enriched with osteostatin (SAGO) or with bone marrow aspirate(SAGB) after implantation for 12 weeks in a 15-mm long critical defect performed in the radius of New Zealand rabbits. Bone formation obtained was compared with a group with the unfilled defect (CE), as control group, and other with the defect filed with iliac crest autograft (GS), as gold standard. X-ray follow-up was performed at 2, 4, 6 and 12 weeks and µCT and histological studies at 12 weeks. The radiological results showed a greater increment in bone formation in the GS group (75%-100%), followed by the SAG and SAGB groups (50%-75%). µCT results showed an increase of bone volume/tissue volume values in GS group followed by SAG and SAGB groups (0.53, 0.40, and 0.31 respectively) compared with CE group (0.26). Histological results showed limited resorption of the nCHA scaffolds and partial osseointegration in the SAG and SAGB groups. However, in the SAGO group, the presence of connective tissue encapsulating the scaffold was detected. In SAG, SAGB, and increase of bone formation were observed compared with CE group, but less than the GS group. Thus, the investigated materials represent a significant advance in the design of synthetic materials for bone grafting, but further studies are needed to bring their in vivo behavior closer to autograft, the gold standard.

Sex differences in autism-like behavior and dopaminergic neurons in substantia nigra of juvenile mice prenatally exposed to valproate.

Autism spectrum disorder (ASD) is characterized by deficits in social interaction and communication and repetitive and restricted behaviors. Sex dimorphism in the brain, including midbrain dopaminergic circuits, can explain differences in social behavior impairment and stereotypic behaviors between male and female individuals with ASD. These abnormal patterns may be due to alterations in dopamine synthesis in the ventral tegmental area (VTA) and substantia nigra (SN). We used an autism-like mouse model by prenatal valproic acid (VPA) exposure. CD1 pregnant female mice were injected with 500 mg/kg VPA or 0.9% NaCl as a vehicle on gestational day 12.5. In the offspring, on postnatal day 31, we examined the social and repetitive behaviors and the number of tyrosine hydroxylase (TH)-positive cells in VTA and SN by sex. Male VPA mice showed impaired social behavior and increased repetitive behaviors when compared to male vehicles. In females, we did not find statistically significant differences in social or repetitive behaviors between the groups. Male VPA mice had fewer TH+ cells in the SN than control-vehicle mice. Interestingly, no cellular changes were observed between females. This study supports the notion that sex dimorphism of certain brain regions is involved in the etiopathogenesis and clinical presentation of ASD.