Genetic determinants of micronucleus formation in vivo.

Genomic instability arising from defective responses to DNA damage1 or mitotic chromosomal imbalances2 can lead to the sequestration of DNA in aberrant extranuclear structures called micronuclei (MN). Although MN are a hallmark of ageing and diseases associated with genomic instability, the catalogue of genetic players that regulate the generation of MN remains to be determined. Here we analyse 997 mouse mutant lines, revealing 145 genes whose loss significantly increases (n = 71) or decreases (n = 74) MN formation, including many genes whose orthologues are linked to human disease. We found that mice null for Dscc1, which showed the most significant increase in MN, also displayed a range of phenotypes characteristic of patients with cohesinopathy disorders. After validating the DSCC1-associated MN instability phenotype in human cells, we used genome-wide CRISPR-Cas9 screening to define synthetic lethal and synthetic rescue interactors. We found that the loss of SIRT1 can rescue phenotypes associated with DSCC1 loss in a manner paralleling restoration of protein acetylation of SMC3. Our study reveals factors involved in maintaining genomic stability and shows how this information can be used to identify mechanisms that are relevant to human disease biology1.

Obstructive Sleep Apnea: a risk for uncontrolled and more severe asthma in adults that we should keep an eye on.

Summary: Background. Asthma control can be influenced by several factors, including obstructive sleep apnea (OSA). The literature reports variable prevalence and magnitude of OSA impact on asthma outcomes. The aim of our study is to analyze the frequency of high-risk for OSA in asthma patients and its impact on disease severity and control. Methods. We conducted a cross-sectional study at an Allergy Department with adult asthma patients recruited while undergoing routine lung function tests. Data on sex, age, body mass index, allergen sensitization, smoking habits, risk of OSA (using the Berlin questionnaire), rhinitis control (through CARAT), asthma severity (based on GINA 2023), asthma control (using the ACT), adherence to asthma treatment (through Treatment Adherence Measure) and pulmonary function test results were collected. Results. We included 216 patients, predominantly women (70.4%), with a median (P25-P75) age of 29.0 (21.0-45.0) years, of whom 28.2% were on GINA treatment levels 4-5. In 75.5% of cases asthma was controlled. High-risk for OSA was identified in 21.8% of patients. Asthma patients with high-risk for OSA were more likely to have uncontrolled [(47.8%; n = 22) vs (15.8%; n = 26); p less than 0.001] and more severe disease [(44.7%; n = 21) vs (23.7%; n = 40), p = 0.006]. In multivariable analysis, high-risk for OSA (OR 2.81 [95%CI 1.1.28-6.17], p = 0.010), sex (women) (OR 5.21 [95% CI 1.70-15.96], p = 0.004), uncontrolled rhinitis (OR 3.65 [95%CI 1.38-9.64], p = 0.009) and GINA asthma treatment steps 4-5 (OR 2.46 [95%CI 1.15-5.26], p = 0.020) were associated with uncontrolled asthma. Conclusions. It is crucial to actively investigate OSA, especially in patients with uncontrolled and more severe forms of asthma.

Atypical histological presentation of bone regeneration after insertion of cryoprotected allogeneic bone graft.

BACKGROUND: To evaluate bone regenerative capacity of cryoprotected corticocancellous allogeneic bone graft performed in type II and III post-extraction sockets for ridge preservation after twelve weeks in-vivo. MATERIAL AND METHODS: Twenty-seven type II or III bony-walled extraction sockets (mandible and maxilla) were selected for this study. Following atraumatic tooth-extraction a cryoprotected corticocancellous allogeneic bone graft material and a resorbable porcine-derived collagen membrane were used for ridge preservation. During re-entry surgery at approximately 12 weeks, bone core biopsies were obtained using a 3.2 mm trephine drill and samples were histologically processed and subjected to qualitative and quantitative histomorphometric analysis. Quantitative data was analyzed using a general linear mixed model with results presented as mean values with the corresponding 95% confidence interval values. RESULTS: Healing without incident and ridge preservation allowed for the placement of dental implants after 12 weeks in 25 out of the 27 treated socket sites. Analyses yielded an average of ~21.0±7% of old/native bone, ~17±5.5% of newly regenerated bone (total of ~38±12.8% for all bone), 0.23±0.14% of new bone presenting with nucleating sites within the matrix, ~52±5.12% of soft tissue, and 3.6±2.09% of damaged bone. The average regenerated bone was statistically analogous to that of old/native bone (p=0.355). Furthermore, an atypical histological pattern of bone regeneration was observed, with newly formed bone exhibiting "infiltration-like" behavior and with new bone nucleating sites observed within the demineralized bone matrix. CONCLUSIONS: Cryoprotected corticocancellous allogeneic bone-graft demonstrated osteoconductive, osteoinductive, and osteogenic properties, yielding unique healing patterns which does warrant further investigation.

The impact of a drug allergy label in an internal medicine ward.

Summary: Background. Drug hypersensitivity reactions are presumably immune-mediated reactions that cause reproducible signs and/or symptoms. Overdiagnosis of drug allergy, frequently self-reported, is common and carries significant limitations. We intended to analyze the frequency and impact of drug allergy in hospitalized patients. Methods. A retrospective study was conducted in an Internal Medicine ward at a tertiary hospital in Portugal. All patients with a drug allergy report admitted within a 3-year period were included. Data were collected from their electronic medical records. Results. We found that 15.4% of patients had a report of drug allergy, with antibiotics being the most common (56.4%), followed by non-steroidal anti-inflammatory drugs (21.7%) and radiocontrast media (7.0%). The allergy report affected the clinical approach of 14.5% of patients by motivating the use of second-line agents, or the eviction of necessary procedures. The usage of alternative antibiotics entailed a cost increase of 2.4 times. There were 14.7% of patients to whom the suspected drug was administered: 87.0% tolerated and 13.0% developed a reaction. Only 1.9% were referred to our Allergy and Clinical Immunology department and proceeded in their allergy study. Conclusions. In this study, a considerable number of patients had a drug allergy label on their records. This label contributed to an increase in the cost of treatment, or the avoidance of necessary exams. However, disregarding an allergy record may lead to potentially life-threatening reactions that proper risk assessment could avoid. Further investigation should always be part of the follow-up routine of these patients, and better articulation between departments should be encouraged.

Impact of implant thread design on insertion torque and osseointegration: a preclinical model.

BACKGROUND: Successful osseointegration of endosteal dental implants has been attributed to implant design, including the macro-, micro- and nano- geometric properties. Based on current literature pertaining to implant design, the resultant cellular and bone healing response is unknown when the thread thickness of the implants is increased, resulting in an increased contact area in implants designed with healing chambers. The aim of this study was to evaluate the effect of two implant designs with different thread profiles on the osseointegration parameters and implant stability at 3- and 6-weeks in vivo using a well-established preclinical dog model. MATERIAL AND METHODS: A total of 48 type V Ti alloy implants were divided in two groups according to their thread design (D1= +0.1x/mm and D2= +0.15x/mm) and placed in an interpolated fashion into the radii of six beagles. Insertion torque was measured at time of placement, radii were extracted for histological processing following 3- and 6-week healing intervals. Histologic and histomorphometric analyses were performed in terms of bone to implant contact (%BIC) and bone area fraction occupancy within implant threads (%BAFO). Statistical analyses were performed through a linear mixed model with fixed factors of time and implant thread design. RESULTS: Surface roughness analysis demonstrated no significant differences in Sa and Sq between D1 and D2 implant designs, which confirmed that both implant designs were homogenous except for their respective thread profiles. For insertion torque, statistically significant lower values were recorded for D1 in comparison to D2 (59.6 ± 11.1 and 78.9 ± 10.1 N⋅cm, respectively). Furthermore, there were no significant differences with respect to histological analysis and histomorphometric parameters, between D1 and D2 at both time points. CONCLUSIONS: Both thread profiles presented equivalent potential to successfully osseointegrate in the osteotomies, with D2 yielding higher mechanical retention upon placement without detrimental bone resorption.

The effect of nano hydroxyapatite coating implant surfaces on gene expression and osseointegration.

BACKGROUND: Hierarchical micro-nano structured topography along with surface chemistry modifications of dental implants have been suggested to positively contribute to the osseointegration process. However, the effect of such surface modifications on the molecular response as well as bone formation rate and quality are still unclear, especially in the early healing period. This study aimed to evaluate the effect of coating a double acid etched (DAE) implant surface with nano-sized (20 nm) hydroxyapatite (Nano) with respect to gene expression, histologic parameters, and nanomechanical properties when compared to DAE control at 1 and 2 weeks after implant placement in a rodent femur model. MATERIAL AND METHODS: Expression of bone-related genes was determined by qRT-PCR (Col-I, Runx-2, Osx, Opn, Ocn, Alp). Histomorphometric evaluation of bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) within implant threads was performed using photomicrographs after histologic processing. Mechanical properties, reduced elastic modulus and hardness, were determined through nanoindentation. RESULTS: At 1 week, the Nano group demonstrated significantly higher expression of Col-I and Ocn compared to the DAE group, indicating upregulation of osteoprogenitor and osteoblast differentiation genes. At 2 weeks, Nano surface further exhibited enhanced gene expression of Col-I and Osx in comparison to the DAE surface, suggesting an increased mineralization of the newly formed bone. Nanoindentation analysis revealed that the Nano group presented no significant difference on the ranks of reduced elastic modulus and hardness compared to DAE for both timepoints. Histomorphometric analysis yielded no significant difference in the percentage of BIC and BAFO between the Nano and DAE surfaces at 1 and 2 weeks. However, Nano implants did present a higher mean value, ~50%, of BIC compared to DAE, ~30%, after 2 weeks in vivo. CONCLUSIONS: While no significant differences were observed in the amount and mechanical properties of newly formed bone, Nano surface positively and significantly increased the expression osteogenic genes compared to DAE surface at early healing periods.

Developing and validating high-value patient digital follow-up services: a pilot study in cardiac surgery.

BACKGROUND: The existing digital healthcare solutions demand a service development approach that assesses needs, experience, and outcomes, to develop high-value digital healthcare services. The objective of this study was to develop a digital transformation of the patients' follow-up service after cardiac surgery, based on a remote patient monitoring service that would respond to the real context challenges. METHODS: The study followed the Design Science Research methodology framework and incorporated concepts from the Lean startup method to start designing a minimal viable product (MVP) from the available resources. The service was implemented in a pilot study with 29 patients in 4 iterative develop-test-learn cycles, with the engagement of developers, researchers, clinical teams, and patients. RESULTS: Patients reported outcomes daily for 30 days after surgery through Internet-of-Things (IoT) devices and a mobile app. The service's evaluation considered experience, feasibility, and effectiveness. It generated high satisfaction and high adherence among users, fewer readmissions, with an average of 7 ± 4.5 clinical actions per patient, primarily due to abnormal systolic blood pressure or wound-related issues. CONCLUSIONS: We propose a 6-step methodology to design and validate a high-value digital health care service based on collaborative learning, real-time development, iterative testing, and value assessment.

Effects of a local single dose administration of growth hormone on the osseointegration of titanium implants.

BACKGROUND: The aim of the present study was to evaluate the effect of different concentrations of growth hormone (GH) on endosteal implant's surface at the early stages of osseointegration. MATERIAL AND METHODS: Sixty tapered acid-etched titanium implants were divided into four groups: i) Collagen, used as a control group; and three experimental groups, where after collagen coating, GH was administered directly to the surface in varying concentrations: ii) 0.265 mg, iii) 0.53 mg, and iv) 1 mg. Implants were placed in an interpolated fashion in the anterior flange of C3, C4 or C5 of 15 sheep with minimum distance of 6 mm between implants. After 3-, 6- and 12-weeks of healing samples were harvested, histologically processed, qualitatively and quantitatively assessed for bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO). RESULTS: Statistical analysis as a function of time in vivo and coating resulted in no significant differences for BIC and BAFO at any evaluation time point. Histological evaluation demonstrated similar osseointegration features for all groups with woven bone formation at 3 weeks and progressive replacement of woven for lamellar bone in close contact with the implant surface and within the implant's threads. CONCLUSIONS: A single local application of growth hormone to the surface of titanium implants did not yield improved implant osseointegration independent of healing time.

Bone regeneration at extraction sockets filled with leukocyte-platelet-rich fibrin: An experimental pre-clinical study.

BACKGROUND: We aimed to histomorphometrically evaluate the effects of Leucocyte-Platelet-Rich Fibrin (L-PRF), with and without the combination of a bone grafting material, for alveolar ridge preservation using an in vivo canine model. MATERIAL AND METHODS: Seven dogs (Female Beagles, ~18-month-old) were acquired for the study. L-PRF was prepared from each individual animal by drawing venous blood and spinning them through a centrifuge at 408 RCF-clot (IntrasSpin, Intra-Lock, Boca Raton, FL). L-PRF membranes were obtained from XPression fabrication kit (Biohorizons Implant Systems, Inc., AL, USA). A split mouth approach was adopted with the first molar mesial and distal socket defects treated in an interpolated fashion of the following study groups: 1) Empty socket (negative control); 2) OSS filled defect 3) L-PRF membrane; and 4) Mix of Bio-Oss® with L-PRF. After six weeks, samples were harvested, histologically processed, and evaluated for bone area fraction occupancy (BAFO), vertical/horizontal ridge dimensions (VRD and HRD, respectively), and area of coronal soft tissue infiltration. RESULTS: BAFO was statistically lower for the control group in comparison to all treatment groups. Defects treated with Bio-Oss® were not statistically different then defects treated solely with L-PRF. Collapsed across all groups, L-PRF exhibited higher degrees of BAFO than groups without L-PRF. Defects filled with Bio-Oss® and Bio-Oss® with L-PRF demonstrated greater maintenance of VRD relative to the control group. Collapsed across all groups, Bio-Oss® maintained the VRD and resulted in less area of coronal soft tissue infiltration compared to the empty defect. Soft tissue infiltration observed at the coronal area was not statistically different among defects filled with L-PRF, Bio-Oss®, and Bio-Oss® with L-PRF. CONCLUSIONS: Inclusion of L-PRF to particulate xenograft did not promote additional bone heading at 6 weeks in vivo. However, we noted that L-PRF alone promoted alveolar socket regeneration to levels comparable to particulate xenografts, suggesting its potential utilization for socket preservation.

Microtomographic reconstruction of mandibular defects treated with xenografts and collagen-based membranes: A pre-clinical minipig model.

BACKGROUND: The goal of this study was to evaluate hard tissue response following guided bone regeneration using commercially available bovine bone grafts and collagen membranes; bilayer collagen membrane and porcine pericardium-based membrane, by means of a non-destructive three-dimensional (3D) computerized volumetric analysis following microtomography reconstruction. MATERIAL AND METHODS: Bone regenerative properties of various bovine bone graft materials were evaluated in the Göttingen minipig model. Two standardized intraosseous defects (15mm x 8mm x 8mm) were created bilaterally of the mandible of eighteen animals (n=72 defects). Groups were nested within the same subject and randomly distributed among the sites: (i) negative control (no graft and membrane), (ii) bovine bone graft/bilayer collagen membrane (BOB) (iii) Bio-Oss® bone graft/porcine pericardium-based membrane (BOJ) and (iv) cerabone® bone graft/porcine pericardium-based membrane (CJ). Samples were harvested at 4, 8, and 12-week time points (n=6 animal/time point). Segments were scanned using computerized microtomography (µCT) and three dimensionally reconstructed utilizing volumetric reconstruction software. Statistical analyses were performed using IBM SPSS with a significance level of 5%. RESULTS: From a temporal perspective, tridimensional evaluation revealed gradual bone ingrowth with the presence of particulate bone grafts bridging the defect walls, and mandibular architecture preservation over time. Volumetric analysis demonstrated no significant difference between all groups at 4 weeks (p>0.127). At 8 and 12 weeks there was a higher percentage of new bone formation for control and CJ groups when compared to BOB and BOJ groups (p<0.039). The natural bovine bone graft group showed more potential for graft resorption over time relative to bovine bone graft, significantly different between 4 and 8 weeks (p<0.003). CONCLUSIONS: Volumetric analysis yielded a favorable mandible shape with respect to time through the beneficial balance between graft resorption/bone regenerative capacity for the natural bovine bone graft.

Assessing osseointegration of metallic implants with boronized surface treatment.

BACKGROUND: Modification of endosteal implants through surface treatments have been investigated to improve osseointegration. Boronization has demonstrated favorable mechanical properties, but limited studies have assessed translational, in vivo outcomes. This study investigated the effect of implant surface boronization on bone healing. MATERIAL AND METHODS: Two implant surface roughness profiles (acid etched, machined) in CP titanium (type II) alloy implants were boronized by solid-state diffusion until 10-15µm boron coating was achieved. The surface-treated implants were placed bilaterally into 5 adult sheep ilia for three and six weeks. Four implant groups were tested: boronized machined (BM), boronized acid-etched (BAA), control machined (CM), and control acid-etched (CAA). Osseointegration was quantified by calculating bone to implant contact (BIC) and bone area fraction occupancy (BAFO). RESULTS: Both implant types treated with boronization had BIC values not statistically different from machined control implants at t=3 weeks, and significantly less than acid-etched control (p<0.02). BAFO values were not statistically different for all 3-week groups except machined control (significantly less at p <0.02). BAFO had a significant downward trend from 3 to 6 weeks in both boronized implant types (p<0.03) while both control implant types had significant increases in BIC and BAFO from 3 to 6 weeks. CONCLUSIONS: Non-decalcified histology depicted intramembranous-like healing/remodeling in bone for controls, but an absence of this dynamic process in bone for boronized implants. These findings are inconsistent with in vitro work describing bone regenerative properties of elemental Boron and suggests that effects of boron on in vivo bone healing warrant further investigation.

Adipocyte proteome and secretome influence inflammatory and hormone pathways in glioma.

Gliomas represent the most common primary malignant brain tumors in adults, with an extremely poor prognosis. Among several risk factors, lifestyle was also recently identified as a major risk factor for the development of primary glioma. In the present study, we explore the relationship between obesity and glioma in a cellular model. Thus, we have study the influence of adipocytes secretome on glioma cell line GL261. Using the 3T3-L1 adipocyte cell line, and its conditioned medium (adipokines-enriched medium), we showed that adipocyte-released factors relate with glioma angiogenic, growth, hormones and metabolic behavior by MALDI-TOF-MS and proteomic array analysis. In a first view, STI1, hnRNPs and PGK1 are under expressed on CGl. Similarly, both carbonic anhydrase and aldose reductase are even suppressed in glioma cells that grown under adipokines-enriched environment. Contrariwise, RFC1, KIF5C, ANXA2, N-RAP and RACK1 are overexpressed in GL261 cell the in the presence of the adipokines-enriched medium. We further identified the factors that are released by adipocyte cells, and revealed that several pro-inflammatory and angiogenic factors, such as IL-6, IL-11, LIF, PAI-1, TNF-α, endocan, HGF, VEGF IGF-I, were secreted to the medium into a high extent, whereas TIMP-1 and SerpinE1 were under expressed on CGl. This study discloses an interesting in vitro model for the study of glioma biology under a "obesity" environment, that can be explored for the understanding of cancer cells biology, for the search of biomarkers, prognostic markers and therapeutic approaches.

Osteogenic parameters surrounding trabecular tantalum metal implants in osteotomies prepared via osseodensification drilling.

BACKGROUND: Surgical fixation of implants into bone for the correction of bone deformities or defects is a traditional approach for skeletal stabilization. Important measures of efficacy of implants include implant stability and osseointegration-the direct interaction between living bone and an implant. Osseointegration depends on successful implant placement and subsequent bone remodeling. This study utilized osseodensification drilling (OD) in a low bone density model using trabecular metal (TM) implants. MATERIAL AND METHODS: Three osteotomy sites, Regular, OD-CW (clockwise), and OD-CCW (counterclockwise), were prepared in each ilium of three female sheep. Drilling was performed at 1100rpm with saline irrigation. Trabecular metal (TM) (Zimmer, Parsippany, NJ, USA) implants measuring 3.7mm in diameter x 10mm length were placed into respective osteotomies. A three-week period post-surgery was given to allow for healing to take place after which all three sheep were euthanized and the ilia were collected. Samples were prepared, qualitatively and quantitatively analyzed using histology micrographs and image analysis software (ImageJ, NIH, Bethesda, MD). Bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) were quantified to evaluate the osseointegration parameters. RESULTS: All implants exhibit successful bone formation in the peri-implant environment as well as within the open spaces of the trabecular network. Osseointegration within the TM (quantified by %BIC) as a function of drilling technique was more pronounced in OD samples(p>0.05). The %BAFO however shows a significant difference (p=0.036) between the CCW and R samples. Greater bone volume and frequency of bone chips are observed in OD samples. CONCLUSION: The utilization of OD as a design for improved fixation of hardware was supported by increased levels of stability, both primary and secondary. Histological data with OD provided notably different results from those of the regular drilling method.

17α-Ethinylestradiol and 17ß-estradiol removal from a secondary urban wastewater using an RBC treatment system.

The presence of micropollutants that include endocrine-disrupting compounds (EDC) in aquatic environments is currently one of the most relevant aspects of water quality due to their adverse effects on aquatic organisms and human health. From the several categories of EDC, 17ß-estradiol (E2) is a natural hormone, which is prevalent in vertebrates, associated with the female reproductive system and maintenance of the sexual characters. 17α-Ethinylestradiol (EE2) is a synthetic hormone produced from the natural hormone E2 and is an essential component of oral contraceptives. These compounds are susceptible to bioconcentration and have high potential to bioaccumulation. Wastewater treatment plants are the main point source of E2 and EE2 into aquatic environments, but conventional wastewater treatment systems are not specifically designed for steroid removal. To overcome this problem, biological tertiary treatment may be a solution for the removal of emergent pollutants such as E2 and EE2. The main purpose of the present study is to provide a solution based on the optimization of a rotating biological contactor system to remove estrogens, specifically E2 and EE2, and to quantify their removal efficiency on different matrices, namely real wastewater and different synthetic wastewaters. All assays presented viable removal efficiencies for compound E2 with values always above 50%; real wastewater yielded the highest removal efficiencies. EE2 removal had better removal efficiencies with synthetic wastewater as feed solution, with removals above 15%, whereas the removal efficiency with real wastewater was inexistent.

Effect of implant placement depth on the peri-implant bone defect configurations in ligature-induced peri-implantitis: An experimental study in dogs.

BACKGROUND: The subcrestal placement of implant platform has been considered a key factor in the preservation of crestal bone, but the influence of implant placement depth on bone remodeling combined with peri-implantitis is not fully understood. The aim of this study was to assess the effect of the crestal or subcrestal placement of implants on peri-implant bone defects of ligature-induced peri-implantitis in dogs. MATERIAL AND METHODS: Eight weeks after tooth extraction in six beagle dogs, two different types of implants (A: OsseoSpeed(TM), Astra, Molndal, Sweden; B: Integra-CP(TM), Bicon, Boston, USA) were placed at either crestal or subcrestal (-1.5 mm) positions on one side of the mandible. Ligature-induced peri-implantitis was initiated four weeks after the installation of the healing abutment connections. After 12 weeks, tissue biopsies were processed for histological analyses. RESULTS: Supra-alveolar bone loss combined with a shallow infrabony defect was observed in crestal level implants while deep and wide infrabony defects were present in subcrestal level groups. Subcrestal groups showed significantly greater ridge loss, depths and widths of infrabony defects when compared to crestal groups (P <0.001). CONCLUSIONS: Within the limitations of the animal study, it can be stated that the implants at subcrestal position displayed greater infra-osseous defect than implants at crestal position under an experimental ligature-induced peri-implantitis.

Home sweet home: evidence for nest-fidelity in the rocky intertidal fish, the shanny Lipophrys pholis.

The ability to be faithful to a particular area or site was analysed in the shanny Lipophrys pholis. Using passive integrated transponders, adults from a population of L. pholis at Cabo Raso, Portugal, were followed over a period of 3 years. The findings showed that site fidelity is a consistent behaviour during the breeding season with specific breeding males being found only in particular sectors within the area, and in specific nests throughout the years. The fact that, in general, L. pholis individuals were absent from the study area during the non-breeding season and breeding males were recorded returning to the same nests and sectors for consecutive breeding seasons suggests that they have developed excellent homing abilities. Translocation data corroborate this idea showing that breeding males successfully returned to their nests after a displacement of >100 m. Altogether, these findings highlight the relevance of life-history traits (e.g. nesting) in the conditioning of site fidelity and homing for this species of rocky intertidal fish, and more importantly, provide evidence for the need of a well-developed navigational system.

The heritable path of human physical performance: from single polymorphisms to the "next generation".

Human physical performance is a complex multifactorial trait. Historically, environmental factors (e.g., diet, training) alone have been unable to explain the basis of all prominent phenotypes for physical performance. Therefore, there has been an interest in the study of the contribution of genetic factors to the development of these phenotypes. Support for a genetic component is found with studies that shown that monozygotic twins were more similar than were dizygotic twins for many physiological traits. The evolution of molecular techniques and the ability to scan the entire human genome enabled association of several genetic polymorphisms with performance. However, some biases related to the selection of cohorts and inadequate definition of the study variables have complicated the already difficult task of studying such a large and polymorphic genome, often resulting in inconsistent results about the influence of candidate genes. This review aims to provide a critical overview of heritable genetic aspects. Novel molecular technologies, such as next-generation sequencing, are discussed and how they can contribute to improving understanding of the molecular basis for athletic performance. It is important to ensure that the large amount of data that can be generated using these tools will be used effectively by ensuring well-designed studies.

A Critical Perspective on Mechanical Testing of Implants and Prostheses.

The degree of interplay among variables in dental implant treatment presents a challenge to randomized clinical trials attempting to answer questions in a timely, unbiased, and economically feasible fashion. Further adding complexity to the different scenarios is the varied implant designs and related bone response, area of implantation, implant bulk material, restoration, abutments and related screws, fixation mode (screwed, fixed, or a combination), and horizontal implant-abutment matching geometry. This article critically appraises the most common mechanical testing methods used to characterize the implant-prostheses complex. It attempts to provide insight into the process of construction of an informed database of clinically relevant questions regarding preclinical evaluation of implant biomechanics and failure mechanisms. The use of single load to failure, fatigue life, fatigue limit, and step-stress accelerated life testing is discussed with emphasis on their deliverables, weaknesses, and strengths. Fractographic analysis and challenges in the correlation between laboratory- and in-service-produced failures of dental ceramics, resin composites, and titanium are introduced. In addition, examples are presented of mechanical characterization studies used in our laboratory to assess some implant-supported rehabilitation variables.

Biomonitoring of several toxic metal(loid)s in different biological matrices from environmentally and occupationally exposed populations from Panasqueira mine area, Portugal.

In the Panasqueira mine area of central Portugal, some environmental media show higher metal(loid) concentrations when compared with the local geochemical background and the values proposed in the literature for these environmental media. In order to evaluate the effect of the external contamination on selected indexes of internal dose, As, Cd, Cu, Cr, Fe, Hg, Mg, Mn, Mo, Ni, Pb, S, Se, Si, and Zn were quantified by inductively coupled plasma mass spectrometry and inductively coupled plasma optical emission spectrometry in blood, urine, hair and nail samples from individuals environmentally (N = 41) and occupationally exposed (N = 41). A matched control group (N = 40) was also studied, and data from the three groups were compared. Results obtained agreed with those reported by environmental studies performed in this area, pointing to populations living nearby and working in the mine being exposed to metal(loid)s originated from mining activities. Arsenic was the element with the highest increase in exposed populations. The concentration of other elements such as Cr, Mg, Mn, Mo, Ni, Pb, S, Se, and Zn was also increased, although at a lesser extent, specifically in the individuals environmentally exposed and in females. These findings confirm the need for competent authorities to act as soon as possible in this area and implement strategies aimed to protect exposed populations and the entire ecosystem.

Preimplantation development of in vitro-produced bovine embryos treated with hydroxychloroquine.

Hydroxychloroquine (HCQ) is a safe antimalarial drug but its overdosage or inappropriate use, such as during the pandemic, may cause adverse effects once this drug is considered a potent inhibitor of autophagy. Information about HCQ's effects on the reproductive field, including gametes and initial embryos, is limited. In this study, we evaluated the effect of HCQ (1, 6, 12, and 24 µM) on pre-implantation embryo development, autophagy, and apoptosis of bovine embryos produced in vitro. A dose-response experiment showed a reduction (p < 0.05) in cleavage only at the highest concentration. Blastocyst rate was gradually reduced (p < 0.05) with the increase of HCQ dosage starting at 6 µM, with no embryo formation occurring at 24 µM. Further analysis showed that embryos treated with 12 µM of HCQ had a higher (p < 0.05) accumulation of acidic autophagic vesicles on Days 5 and 7 of development and a higher (p < 0.01) apoptotic index on Day 7. To our knowledge, this is the first study to evaluate the effects of HCQ on embryo pre-implantation development in mammals. The results contribute with more information related to the study of autophagy in embryology as well as add some discussion on HCQ toxicology and its effects on reproductive cells.