Gastric Cancer in the Era of Epigenetics.

Gastric cancer (GC) remains a significant contributor to cancer-related mortality. Novel high-throughput techniques have enlightened the epigenetic mechanisms governing gene-expression regulation. Epigenetic characteristics contribute to molecular taxonomy and give rise to cancer-specific epigenetic patterns. Helicobacter pylori (Hp) infection has an impact on aberrant DNA methylation either through its pathogenic CagA protein or by inducing chronic inflammation. The hypomethylation of specific repetitive elements generates an epigenetic field effect early in tumorigenesis. Epstein-Barr virus (EBV) infection triggers DNA methylation by dysregulating DNA methyltransferases (DNMT) enzyme activity, while persistent Hp-EBV co-infection leads to aggressive tumor behavior. Distinct histone modifications are also responsible for oncogene upregulation and tumor-suppressor gene silencing in gastric carcinomas. While histone methylation and acetylation processes have been extensively studied, other less prevalent alterations contribute to the development and migration of gastric cancer via a complex network of interactions. Enzymes, such as Nicotinamide N-methyltransferase (NNMT), which is involved in tumor's metabolic reprogramming, interact with methyltransferases and modify gene expression. Non-coding RNA molecules, including long non-coding RNAs, circular RNAs, and miRNAs serve as epigenetic regulators contributing to GC development, metastasis, poor outcomes and therapy resistance. Serum RNA molecules hold the potential to serve as non-invasive biomarkers for diagnostic, prognostic or therapeutic applications. Gastric fluids represent a valuable source to identify potential biomarkers with diagnostic use in terms of liquid biopsy. Ongoing clinical trials are currently evaluating the efficacy of next-generation epigenetic drugs, displaying promising outcomes. Various approaches including multiple miRNA inhibitors or targeted nanoparticles carrying epigenetic drugs are being designed to enhance existing treatment efficacy and overcome treatment resistance.

Sperm plasma membrane ion transporters and male fertility potential: A perspective under the prism of cryopreservation.

Intracellular calcium homeostasis plays a crucial role in spermatozoa by regulating physiological functions associated with sperm quality and male fertility potential. Intracellular calcium fine balance in the sperm cytoplasm is strictly dependent on sperm surface channels including the CatSper channel. CatSpers' role is to ensure the influx of extracellular calcium, while intracellular pH alkalinization serves as a stimulus for the activation of several channels, including CatSper. Overall, the generation of intracellular calcium spikes through CatSper is essential for fertilization-related processes, such as sperm hyperactivation, acrosome reaction, egg chemotaxis, and zona pellucida penetration. Multiple lines of evidence suggest that disruption in the close interaction among ions, pH, and CatSper could impair male fertility potential. In contemporary times, the growing reliance on Medically Assisted Reproduction procedures underscores the impact of cryopreservation on gametes. In fact, a large body of literature raises concerns about the cryo-damages provoked by the freeze-thawing processes, that can affect the plasma membrane integrity, thus the structure of pivotal ion channels, and the fine regulation of both intracellular calcium and pH. This review aims to provide an overview of the importance of the CatSper channel in sperm quality and further fertilization potential. Additionally, it addresses the emerging issue of cryopreservation's impact on the functionality of this sperm channel.

Construction and validation of the community health workers perception questionnaire on conditions amenable to physiotherapy in primary health care / Construção e validação do questionário de percepção dos Agentes Comunitários de Saúde sobre condições sensíveis à fisioterapia na Atenção Primária

Abstract Introduction Community health workers, like the physiotherapist, perform essential functions in primary health care, being an important element in the transformation of public policies. There are no reported studies investigating the knowledge of community health workers about health conditions amenable to physiotherapy intervention in primary health care. Objective To construct a questionnaire to investigate the perception of community health workers about health conditions that could be remedied by physiotherapy intervention in primary health care. Methods This was a methodological study in which it was initially an analysis matrix with the aim of encompassing the ideas contemplated in the questionnaire. To construct the instrument, a literature review was carried out, and health conditions treatable with physiotherapy in primary health care were chosen. To validate the content and appearance of the items, twelve physiotherapists specialized in primary health care judged the suitability of the items contained. The content validity index was used to determine the degree of agreement during the response analysis process. Subsequently, a semantic analysis was carried out through the understanding of the items by 15 community health workers. In the validation stage, two rounds of evaluation were carried out. Adjustments were made to 17 questions. Results The study investigated a questionnaire with 20 questions containing hypothetical situations of home visits, in which the resident's situation could or could not constitute a health risk amenable to physiotherapeutic intervention. Conclusion The community health workers perception instrument on health conditions amenable to physiotherapy intervention in primary health care proved to be valid for use in this context. The use of the instrument may contribute to the development of community health worker training programs, with the aim of facilitating team communication.

Resumo Introdução O Agente Comunitário de Saúde (ACS), assim como o fisioterapeuta, desencadeia funções fundamentais na Atenção Primária à Saúde (APS), sendo ele-mento importante na transformação de políticas públicas. Inexistem estudos que investiguem o conhecimento dos ACS sobre as condições de saúde sensíveis à inter-venção da fisioterapia na APS. Objetivo Construir um questionário de investigação da percepção dos ACS sobre as condições de saúde sensíveis à intervenção da fisioterapia na APS. Métodos Trata-se de um estudo metodológico no qual, inicialmente, construiu-se uma matriz de análise com o intuito de englobar as ideias contempladas no questionário. Para a construção do instrumento, realizou-se uma revisão da literatura, sendo eleitas condições de saúde sensíveis à intervenção da fisioterapia na APS. Para a validação de conteúdo e aparente dos itens, 12 fisioterapeutas especialistas em APS julgaram a adequação dos itens contidos. Utilizou-se o índice de validade de conteúdo para verificar o grau de concordância durante o processo de análise das respos-tas. Posteriormente, realizou-se análise semântica por meio da compreensão dos itens por 15 ACS. Na etapa de validação, foram realizadas duas rodadas de avaliação. Foram feitos ajustes em 17 questões. Resultados O estudo resultou em um questionário com 20 questões contendo situações hipotéticas de visitas domiciliares, cuja situação do morador poderia ou não configurar um risco à saúde sensível à intervenção fisioterapêutica. Conclusão O instrumento de percepção dos ACS sobre as condições de saúde sensíveis à intervenção da fisioterapia na APS mostrou-se válido para ser utilizado no contexto da APS. A utilização do instrumento poderá contribuir na elaboração de programas de capacitação dos ACS, com o intuito de facilitar a comunicação da equipe.

Characterization of a miRNA Signature with Enhanced Diagnostic and Prognostic Power for Patients with Bladder Carcinoma.

Bladder carcinoma is globally among the most prevalent cancers and is associated with a high mortality rate at advanced stages. Its detection relies on invasive diagnostic methods that are unpleasant for the patient. Non-invasive molecular biomarkers, such as miRNAs, could serve as alternatives for early detection and prognosis of this malignancy. We designed a computational approach that combines transcriptome profiling, survival analyses, and calculation of diagnostic power in order to isolate miRNA signatures with high diagnostic and prognostic utility. Our analysis of TCGA-BLCA data from 429 patients yielded one miRNA signature, consisting of five upregulated and three downregulated miRNAs with cumulative diagnostic power that outperforms current diagnostic methods. The same miRNAs have a strong prognostic significance since their expression is associated with the overall survival of bladder cancer patients. We evaluated the expression of this signature in 19 solid cancer types, supporting its unique diagnostic utility for bladder carcinoma. We provide computational evidence regarding the functional implications of this miRNA signature in cell cycle regulation, demonstrating its abundance in body fluids, including peripheral blood and urine. Our study characterized a novel miRNA signature with the potential to serve as a non-invasive method for bladder cancer diagnosis and prognosis.

The Genomic Signatures of Linitis Plastica Signal the Entrance into a New Era: Novel Approaches for Diagnosis and Treatment.

Linitis Plastica (LP) is a rare and aggressive tumor with a distinctive development pattern, leading to the infiltration of the gastric wall, the thickening of the gastric folds and a "leather bottle appearance". LP is an extremely heterogeneous tumor caused by mutations in oncogenic and tumor suppressive genes, as well as molecular pathways, along with mutations in stromal cells and proteins related to tight junctions. Elucidating the molecular background of tumorigenesis and clarifying the correlation between cancerous cells and stromal cells are crucial steps toward discovering novel diagnostic methods, biomarkers and therapeutic targets/agents. Surgery plays a pivotal role in LP management, serving both as a palliative and curative procedure. In this comprehensive review, we aim to present all recent data on the molecular background of LP and the novel approaches to its management.

The impact of cryopreservation on both sperm HPV-negative and positive subtypes.

It is well known that various human papillomavirus (HPV) genotypes are present in semen specimens. Also, it has been demonstrated that sperm parameters are negatively affected when HPV infection is present in the sperm sample. Besides all these, the effect of cryopreservation on HPV sensitivity and resistance is not known. The aim of the present study is to evaluate first the prevalence of HPV and secondly to elucidate whether cryopreservation of sperm HPV-positive samples has any effect on the viability of HPV. For this purpose, a cohort of 78 sperm specimens was used from a respective number of patients. After giving informed consent, semen analysis was performed. Each sperm sample was divided into four equal aliquots. The first one (fresh) was evaluated for the prevalence of HPV, while the other three aliquots were cryopreserved by adding an equal quantity of cryoprotectant and plunged into the LN. Each of the three aliquots was thawed 3, 6, and 12 months later, respectively, so as to evaluate whether there is a time-resistance period of HPV prevalence. HPV infection was found to be in eleven sperm samples, demonstrating a 14.1% (11/78) HPV prevalence. Among the HPV-positive samples, six of them were high-risk and the remaining were low-risk genotypes. Moreover, the high-risk fresh samples demonstrated higher motility values than the low-risk samples (60% ± 2.7 vs 45.6% ± 3.7, p < .05), while semen volume in the high-risk samples was significantly lower than the respective volume in the low-risk samples (2.26 ± 0.2ml vs 3.5 ± 0.6ml, p < .05). Interestingly, cryopreservation of the HPV-positive samples resulted in the sustainability and time-resistance of HPV in all high-risk HPV-positive samples, something that was not the case with the low-risk HPV-positive samples. Conclusively, sperm samples infected with high-risk HPV, demonstrate lower sperm parameters and time-resistance activity during cryopreservation.

Telerreabilitação na fisioterapia neurofuncional pediátrica durante a pandemia de COVID-19: percepção dos pais, desafios e contribuições / Telerehabilitation in pediatric neurofunctional physical therapy during the COVID-19 pandemics: parent's perception, challenges and contributions

INTRODUÇÃO: A telerreabilitação é uma modalidade de atendimento realizado à distância que foi considerada um recurso fundamental durante a pandemia da COVID-19. Entretanto, era uma modalidade ainda não vivenciada por muitos profissionais e familiares. OBJETIVO: Descrever a percepção dos pais ou responsáveis por crianças em tratamento fisioterapêutico, sobre os desafios e as contribuições da experiência com a telerreabilitação realizada em serviço ambulatorial durante a pandemia de COVID-19. MATERIAIS E MÉTODOS: Estudo observacional transversal exploratório, realizado com pais ou responsáveis por crianças, com idade entre 0 a 12 anos, com qualquer condição de saúde neurológica ou musculoesquelética em acompanhamento fisioterapêutico por telerreabilitação, no período de junho a agosto de 2021. Um questionário elaborado pelas autoras com perguntas sobre a percepção dos responsáveis, desafios e contribuições da telerreabilitação foi encaminhado para os responsáveis por meio de um link do Google Forms, via e-mail ou aplicativo de mensagem no celular, e foi auto aplicado. Realizaramse análises descritivas dos dados coletados por meio da frequência de respostas dos pais ou responsáveis nas questões específicas. As variáveis numéricas foram apresentadas como média ± desvio-padrão e as variáveis categóricas, como frequências absolutas e relativas. RESULTADOS: Dezoito responsáveis receberam e responderam o questionário completamente. A mãe foi a responsável mais citada, a maioria das crianças recebeu atendimento duas vezes na semana e o diagnóstico mais prevalente foi paralisia cerebral. Setenta e três por cento dos responsáveis avaliaram a telerreabilitação como acima do nível esperado e com contribuição além de suas expectativas. CONCLUSÃO: De acordo com a percepção dos pais, sobre os desafios e as contribuições da experiência com a telerreabilitação realizada em serviço ambulatorial, os benefícios parecem superar os desafios.

INTRODUCTION: Telerehabilitation is a modality of care provided remotely that was considered a fundamental resource during the COVID-19 pandemic. However, it was a modality not yet experienced by many professionals and family members. OBJECTIVE: To describe the perception of parents or guardians of children undergoing physical therapy, about the challenges and contributions of the experience with telerehabilitation performed in an outpatient service during the COVID-19 pandemics. MATERIAL AND METHODS: An exploratory crosssectional observational study carried out with parents or guardians of children, aged between 0 and 12 years old, with any neurological or musculoskeletal health condition in physiotherapeutic treatment by telerehabilitation, from June to August 2021. A questionnaire prepared by the authors with questions about the perception of those responsible, challenges and contributions of telerehabilitation was sent to those responsible through a Google Forms link, by email or mobile messaging app and was self-applied. Descriptive analysis of the data collected was carried out through the frequency of responses from parents or guardians on specific questions. Numerical variables were presented as mean ± standard deviation and categorical variables as absolute and relative frequencies. RESULTS: Eighteen guardians received and answered the questionnaire completely. The mother was the most cited guardian, most children received care twice a week and the most prevalent diagnosis was cerebral palsy. Seventythree percent of those responsible rated telerehabilitation as above the expected level and with a contribution beyond their expectations. According to them, the greatest contribution of telerehabilitation was the satisfactory motor development presented by the children during the period of social isolation. CONCLUSION: According to the parents' perception of the challenges and contributions of the experience with telerehabilitation performed in outpatient service, the benefits seem to outweigh the challenges.

Odontologia do Trabalho: o estado da arte, indicando trilhas para a promoção da saúde em contextos contemporâneos de labor - revisão de escopo / Occupational Dentistry: the state of the art, indicating paths for health promotion in contemporary work contexts - scoping review

Resumo O campo da Odontologia do Trabalho tem considerado lastro teórico-científico. Esta revisão de escopo objetiva desvelar o estado da arte acerca do tema em sete bases de pesquisas indexadas, considerando quase 100 anos de publicações (1921-2020). Das 337 produções inicialmente identificadas, realizou-se recorte para os últimos seis anos (2015-2021/janeiro), aplicando-se metodologia proposta pela extensão do Prisma para revisões de escopo (Prisma-ScR). Contudo, plataformas de revisões rápidas usadas para tomada de decisões em formulações de políticas públicas ou em aperfeiçoamentos de sistemas de saúde responderam por apenas 20 publicações, enquanto a amostra de 34 produções revelou peculiaridades: pesquisas privilegiam regimes de trabalho; associam o campo de estudo e prática ao modelo stricto sensu da saúde ocupacional; desconsideram concepções amplas e humanizantes do campo da Saúde do Trabalhador; tendem a priorizar a própria saúde ocupacional odontológica e parecem reduzir o conceito do acidente de trabalho a doenças. Tais questões precisam ser superadas se a perspectiva for manter-se em vanguarda, promovendo saúd e e segurança em contextos contemporâneos de trabalho, pois, embora seja evidente a transversalidade desse campo de saberes e práticas, é necessário mais, é preciso ousar para retirá-la da invisibilidade, seja em organizações privadas ou públicas de trabalho.

Abstract The field of Occupational Dentistry has considered theoretical-scientific ballast. This scoping review aims to reveal the state of the art on the subject in seven indexed research bases, considering almost 100 years of publications (1921-2020). Of the 337 productions initially identified, a cut was made for the last six years (2015-2021/January), applying the methodology proposed by the PRISMA extension for scope reviews (PRISMA-ScR). However, rapid review platforms used for decision making in formulating public policies or in improving health systems accounted for only 20 publications, whereas the sample of 34 productions revealed peculiarities: research favors work regimes; associates the field of study and practice with the stricto sensu model of occupational health; disregards broad and humanizing concepts in the field of Worker's Health; tends to prioritize its own occupational dental health, and seems to reduce the concept of work accidents to illnesses. Such issues need to be overcome if the perspective is to remain at the forefront, promoting health and safety in contemporary work contexts, since, although the transversality of this field of knowledge and practices is evident, more is needed, daring to remove it from invisibility whether in private or public work organizations is necessary.

Immune-based treatment re-challenge in renal cell carcinoma: A systematic review and meta-analysis.

Introduction: The use of immune checkpoint inhibitors (ICIs) as a front-line treatment for metastatic renal cell carcinoma (RCC) has significantly improved patient' outcome. However, little is known about the efficacy or lack thereof of immunotherapy after prior use of anti-PD1/PD-L1 or/and anti-CTLA monoclonal antibodies. Methods: Electronic databases, including PubMed, EMBASE, Medline, Web of Science, and Cochrane Library, were comprehensively searched from inception to July 2022. Objective response rates (ORR), progression-free survival (PFS), and ≥ grade 3 adverse events (AEs) were assessed in the meta-analysis, along with corresponding 95% confidence intervals (CIs) and publication bias. Results: Ten studies which contained a total of 500 patients were included. The pooled ORR was 19% (95% CI: 10, 31), and PFS was 5.6 months (95% CI: 4.1, 7.8). There were ≥ grade 3 AEs noted in 25% of patients (95% CI: 14, 37). Conclusion: This meta-analysis on different second-line ICI-containing therapies in ICI-pretreated mRCC patients supports a modest efficacy and tolerable toxicity.

Hypoxia-Inducible Factor-2-Altered Urothelial Carcinoma: Clinical and Genomic Features.

Background: Hypoxia is recognized as a key feature of cancer growth and is involved in various cellular processes, including proliferation, angiogenesis, and immune surveillance. Besides hypoxia-inducible factor 1-alpha (HIF-1α), which is the main mediator of hypoxia effects and can also be activated under normoxic conditions, little is known about its counterpart, HIF-2. This study focused on investigating the clinical and molecular landscape of HIF-2-altered urothelial carcinoma (UC). Methods: Publicly available next-generation sequencing (NGS) data from muscle-invasive UC cell lines and patient tumor samples from the MSK/TCGA 2020 cohort (n = 476) were interrogated for the level of expression (mRNA, protein) and presence of mutations, copy number variations, structural variants in the EPAS1 gene encoding HIF-2, and findings among various clinical (stage, grade, progression-free and overall survival) and molecular (tumor mutational burden, enriched gene expression) parameters were compared between altered and unaltered tumors. Results: 19% (7/37) of UC cell lines and 7% (27/380) of patients with muscle-invasive UC display high EPAS1 mRNA and protein expression or/and EPAS1 alterations. EPAS1-altered tumors are associated with higher stage, grade, and lymph node metastasis as well as with shorter PFS (14 vs. 51 months, q = 0.01) and OS (15 vs. 55 months, q = 0.01). EPAS1 mRNA expression is directly correlated with that of its target-genes, including VEGF, FLT1, KDR, DLL4, CDH5, ANGPT1 (q < 0.001). While there is a slightly higher tumor mutational burden in EPAS1-altered tumors (9.9 vs. 4.9 mut/Mb), they are enriched in and associated with genes promoting immune evasion, including ARID5B, SPINT1, AAK1, CLIC3, SORT1, SASH1, and FGFR3, respectively (q < 0.001). Conclusions: HIF-2-altered UC has an aggressive clinical and a distinct genomic and immunogenomic profile enriched in angiogenesis- and immune evasion-promoting genes.

Current Options for Second-Line Systemic Therapy in Metastatic Renal Cell Carcinoma.

Standard systemic therapy of advanced renal cell carcinoma (RCC) involves targeting angiogenesis, mainly through tyrosine kinase inhibitors (TKI) against the vascular endothelial growth factor receptor (VEGFR) pathway and targeting the immune checkpoints, namely, programmed death-1 (PD-1) or its ligand (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA4). With current strategies of combining these two approaches in the front-line setting, less is known about optimal selection of therapy upon development of resistance in the second and later lines of treatment for progressive disease. This review discusses currently available therapeutic options in patients who have progressive RCC after prior treatment with double immune check-point inhibitors (ICIs) or ICI-TKI combinations.

Genetic Analysis and Status of Brown Bear Sub-Populations in Three National Parks of Greece Functioning as Strongholds for the Species' Conservation.

In order to optimize the appropriate conservation actions for the brown bear (Ursus arctos L.) population in Greece, we estimated the census (Nc) and effective (Ne) population size as well as the genetic status of brown bear sub-populations in three National Parks (NP): Prespa (MBPNP), Pindos (PINDNP), and Rhodopi (RMNP). The Prespa and Pindos sub-populations are located in western Greece and the Rhodopi population is located in eastern Greece. We extracted DNA from 472 hair samples and amplified through PCR 10 microsatellite loci. In total, 257 of 472 samples (54.5%) were genotyped for 6-10 microsatellite loci. Genetic analysis revealed that the Ne was 35, 118, and 61 individuals in MBPNP, PINDNP, and RMNP, respectively, while high levels of inbreeding were found in Prespa and Rhodopi but not in Pindos. Moreover, analysis of genetic structure showed that the Pindos population is genetically distinct, whereas Prespa and Rhodopi show mutual overlaps. Finally, we found a notable gene flow from Prespa to Rhodopi (10.19%) and from Rhodopi to Prespa (14.96%). Therefore, targeted actions for the conservation of the bears that live in the abovementioned areas must be undertaken, in order to ensure the species' viability and to preserve the corridors that allow connectivity between the bear sub-populations in Greece.

Septotemporal variation in modulation of synaptic transmission, paired-pulse ratio and frequency facilitation/depression by adenosine and GABAB receptors in the rat hippocampus.

Short-term synaptic plasticity represents a fundamental mechanism in neural information processing and is regulated by neuromodulators. Here, using field recordings from the CA1 region of adult rat hippocampal slices, we show that excitatory synaptic transmission is suppressed by strong but not moderate activation of adenosine A1 receptors by 2-Chloro-N6-cyclopentyladenosine (CCPA) more in the dorsal than the ventral hippocampus; in contrast, both mild and strong activation of GABAB receptors by baclofen (1 µM, 10 µM) suppress synaptic transmission more in the ventral than the dorsal hippocampus. Using a 10-pulse stimulation train of variable frequency, we found that CCPA modulates short-term synaptic plasticity independently of the suppression of synaptic transmission in both segments of the hippocampus and at stimulation frequencies greater than 10 Hz. However, specifically regarding the paired-pulse ratio (PPR) and frequency facilitation/depression (FF/D) we found significant drug action before but not after adjusting conditioning responses to control levels. Activation of GABABRs by baclofen suppressed synaptic transmission more in the ventral than the dorsal hippocampus. Furthermore, relatively high (10 µM) but not low (1 µM) baclofen concentration enhanced both PPR and FF in both hippocampal segments at stimulation frequencies greater than 1 Hz, independently of the suppression of synaptic transmission by baclofen. These results show that A1Rs and GABABRs control synaptic transmission more effectively in the dorsal and the ventral hippocampus, respectively, and suggest that these receptors modulate PPR and FF/D at different frequency bands of afferent input, in both segments of the hippocampus.

Negative neuromuscular and functional repercussion of forced swimming after axonotmesis.

Peripheral nerve injuries are cause of sensory disturbances and in functional abilities, and are associated personal and social costs. Strategies that maximize nerve regeneration and functional recovery are necessary, the exercise is an option. This study evaluated the effects of forced swimming exercise on neuromuscular histomorphometry and on functional recovery in a median nerve crush model. Sixteen Wistar rats underwent median nerve crush and were divided into control group (CG) and swimming group (SG). The forced swimming protocol started one week after the injury and was performed for 1 hr a day, 5 days per week, for 2 weeks. The rats swam with an overload of 5% and 10% of body weight in the first and second week, respectively. The functional recovery was assessed in three moments using the grasping test. On day 21, fragments of the median nerve and of the forearm flexors muscles were removed for histomorphometric analysis. The SG had functional recovery impaired (P<0.001) and presented lower myelinated fibers number, fiber and axon minimal diameter, myelin thickness and g-ratio in the proximal e distal segments of the median nerve (P<0.005) and area muscle fiber (P<0.005) than CG. Also, the SG presented a number of capillaries in the proximal segments of the median nerve greater than CG (P<0.005). The exercise protocol used in this study impaired the regeneration of the median nerve and negatively influenced the functional recovery.

Renin-Angiotensin System Single Nucleotide Polymorphisms Are Associated with Bladder Cancer Risk.

The renin-angiotensin system (RAS), besides being a major regulator of blood pressure, is also involved in tumor angiogenesis. Emerging evidence suggests a correlation between the use of pharmacologic RAS inhibitors and a delay in urothelial bladder cancer (BC) progression. However, it is unknown whether RAS gene variants may predispose to the development of BC. This study examined the association of RAS single nucleotide polymorphisms (SNPs) including AT1R rs5186, AT2R rs11091046, REN rs12750834, ANG rs4762, and ANG rs699 with the risk of developing non-invasive BC. Peripheral blood samples from 73 patients with T1 urothelial BC (66 men, seven women) and an equal number of healthy subjects (control group) were collected. The TT genotype of the REN rs12750834 SNP (OR: 2.8 [1.3-6.05], p = 0.008) and to a lesser extent the presence of the T allele (OR: 2.3 [1.2-4.48], p = 0.01) conferred a higher risk of BC. The highest risk for BC within SNP carriers of the RAS system was associated with the presence of the CC genotype (OR: 17.6 [7.5-41.35], p < 0.001) and C allele (OR: 17.7 [8.8-35.9], p < 0.001) of the ANG rs699 SNP. The presence of the AT2R rs11091046 SNP, particularly the AA genotype, was associated with a protective effect against developing BC (OR: 0.268 [0.126-057], p < 0.001). In conclusion, these results support the clinical utility of RAS gene SNPs AT2R rs11091046, REN rs12750834, and ANG rs699 in the genetic cancer risk assessment of patients and families with BC.

Insights into the Role of Telomeres in Human Embryological Parameters. Opinions Regarding IVF.

Telomeres promote genome integrity by protecting chromosome ends from the activation of the DNA damage response and protecting chromosomes from the loss of coding sequences due to the end replication problem. Telomere length (TL) is progressively shortened as age progresses, thus resulting in cellular senescence. Therefore, TL is in strong adverse linear correlation with aging. Mounting evidence supports the notion that telomeres and male/female infertility are in a close relationship, posing the biology of telomeres as a hot topic in the era of human-assisted reproduction. Specifically, the length of sperm telomeres is gradually increasing as men get older, while the telomere length of the oocytes seems not to follow similar patterns with that of sperm. Nonetheless, the telomere length of the embryos during the cleavage stages seems to have a paternal origin, but the telomere length can be further extended by telomerase activity during the blastocyst stage. The latter has been proposed as a new molecular biomarker with strong predictive value regarding male infertility. As far as the role of telomeres in assisted reproduction, the data is limited but the length of telomeres in both gametes seems to be affected mainly by the cause of infertility rather than the assisted reproductive therapy (ART) procedure itself. The present review aims to shed more light into the role of telomeres in human embryological parameters, including gametes and embryos and also presents opinions regarding the association between telomeres and in vitro fertilization (IVF).

Validity of the modified sphygmomanometer test for the assessment of tip pinch strength in Parkinson's disease.

BACKGROUND: The tip pinch is one of the most delicate and precise movement of the hand, and it is used to manipulate small objects, commonly observed in the activities of daily living of any individuals. Individuals with Parkinson Disease (PD) with impaired manual dexterity, manipulative skills, and hand weakness have an important barrier for activities of daily life. However, the dynamometer usually used for measuring the tip pinch have a high cost, so, validate a sphygmomanometer can make this assessment more accessible. OBJECTIVE: To investigate the validity of the modified sphygmomanometer test in the evaluation of tip pinch strength when compared to the gold standard. METHODS: 50 individuals with idiopathic PD took part in the study. The muscle strength of tip pinch on the dominant and non-dominant side was measured by the modified sphygmomanometer test and the gold standard, the dynamometer. Concurrent validity was analyzed using Pearson's correlation coefficient. RESULTS: 50 individuals diagnosed with idiopathic PD, mean age of 67 ± 8.0 years, 68% male, mean time of diagnosis in months of 84 ± 66 and Hoehn and Yahr mean of 2.5 ± 0.6. There was a significant correlation of moderate magnitude between the modified sphygmomanometer test and the dynamometer in dominant side (r = 0.44; p < 0.01) and non-dominant side (r = 0.48; p < 0.01). CONCLUSION: The modified sphygmomanometer test showed adequate validity for assessing the muscle strength of the tip pinch in individuals with PD.

Sown Wildflowers Enhance Habitats of Pollinators and Beneficial Arthropods in a Tomato Field Margin.

We evaluated the capacity of selected plants, sown along a processing tomato field margin in central Greece and natural vegetation, to attract beneficial and Hymenoptera pollinating insects and questioned whether they can distract pollinators from crop flowers. Measurements of flower cover and attracted pollinators and beneficial arthropods were recorded from early-May to mid-July, during the cultivation period of the crop. Flower cover was higher in the sown mixtures compared to natural vegetation and was positively correlated with the number of attracted pollinators. The sown Glebionis coronaria, Coriandrum sativum, Anethum graveolens, and Fagopyrum esculentum attracted mainly wild bees, which were the most abundant pollinating insects. In the natural vegetation, Rapistrum rugosum attracted mainly honeybees, while Asteraceae, Convolvulaceae, and Apiaceae species attracted wild bees. Beneficial arthropod abundance and diversity were higher in the sown mixture. Tomato flowers were visited by a small number of wild bees. Their number was not affected by the distance from the field margin, indicating no distraction effect from the sown or natural vegetation flowering plants. Our results suggest that selected flowering plants can improve the field margin habitats for pollinating insects and beneficial arthropods, but more work is needed to elucidate the effect on crop pollination.

DNA Repair Gene Polymorphisms and Susceptibility to Urothelial Carcinoma in a Southeastern European Population.

Single nucleotide polymorphisms (SNPs) in DNA repair genes may predispose to urothelial carcinoma of the bladder (UCB). This study focused on three specific SNPs in a population with high exposure to environmental carcinogens including tobacco and alcohol. A case-control study design was used to assess for presence of XPC PAT +/-, XRCC3 Thr241Met, and ERCC2 Lys751Gln DNA repair gene SNPs in peripheral blood from patients with UCB and healthy individuals. One hundred patients and equal number of healthy subjects were enrolled. The XPC PAT +/+ genotype was associated with a 2-fold increased risk of UCB (OR = 2.16; 95%CI: 1.14-4; p = 0.01). The -/+ and +/+ XPC PAT genotypes were more frequently present in patients with multiple versus single tumors (p = 0.01). No association was detected between ERCC2 Lys751Gln genotypes/alleles, and risk for developing UCB. Presence of the XRCC3 TT genotype (OR = 0.14; 95%CI:0.07-0.25; p < 0.01) and of the T allele overall (OR = 0.26; 95%CI:0.16-0.41; p < 0.01) conferred a protective effect against developing UCB. The XPC PAT -/+ and XRCC3 Thr241Met SNPs are associated with predisposition to UCB. The XPC PAT -/+ SNP is also an indicator of bladder tumor multiplicity, which might require a more individualized surveillance and treatment.

Predictors of physical activity levels in individuals with Parkinson's disease: a cross-sectional study.

BACKGROUND: To investigate whether modifiable predictors (depressive symptoms, impairment in behavior and mood, balance impairments, and knee extensor muscle strength) are determinants of the physical activity level in Parkinson's disease. MATERIALS AND METHODS: A cross-sectional study with individuals diagnosed with idiopathic Parkinson's disease. Regression analysis of the data was used to investigate whether depressive symptoms, impairments in behavior and mood, balance impairments, or dominant knee extensor muscle strength are predictors of physical activity levels in Parkinson's disease. RESULTS: A total of 50 individuals with mild to moderate Parkinson's disease participated in this study, with a mean age of 67 ± 8 years and 68% male. Balance impairments explained 29% of the variation in the physical activity levels. The explained variance increased to 34% when depressive symptoms were included in the model. CONCLUSION: Among the predictor variables investigated in our study, only balance impairments and depressive symptoms explained the variance in physical activity levels in individuals with Parkinson's disease.