Electrical impedance characterization and modelling of Ti-Β implants.

Commercially pure titanium (c.p. Ti) and Ti6Al4V alloys are the most widely used metallic biomaterials in the biomedical sector. However, their high rigidity and the controversial toxicity of their alloying elements often compromise their clinical success. The use of porous ß-Titanium alloys is proposed as a solution to these issues. In this regard, it is necessary to implement economic, repetitive, and non-destructive measurement techniques that allow for the semi-quantitative evaluation of the chemical nature of the implant, its microstructural characteristics, and/or surface changes. This study proposes the use of simple measurement protocols based on electrical impedance measurements, correlating them with the porosity inherent to processing conditions (pressure and temperature), as well as the chemical composition of the implant. Results revealed a clear direct relationship between porosity and electrical impedance. The percentage and/or size of the porosity decrease with an increase in compaction pressure and temperature. Moreover, there is a notable influence of the frequency used in the measurements obtained. Additionally, the sensitivity of this measurement technique has enabled the evaluation of differences in chemical composition and the detection of intermetallics in the implants. For the first time in the literature, this research establishes relationships between stiffness and electrical impedance, using approximations and models for the observed trends. All the results obtained corroborate the appropriateness of the technique to achieve the real-time characterization of Titanium implants, in an efficient and non-invasive way.

Automated fiducial-based alignment of cryo-electron tomography tilt series in Dynamo.

With the advent of modern technologies for cryo-electron tomography (cryo-ET), high-quality tilt series are more rapidly acquired than processed and analyzed. Thus, a robust and fast-automated alignment for batch processing in cryo-ET is needed. While different software packages have made available several approaches for automated marker-based alignment of tilt series, manual user intervention remains necessary for many datasets, thus preventing high-throughput tomography. We have developed a MATLAB-based framework integrated into the Dynamo software package for automatic detection of fiducial markers that generates a robust alignment model with minimal input parameters. This approach allows high-throughput, unsupervised volume reconstruction. This new module extends Dynamo with a large repertory of tools for tomographic alignment and reconstruction, as well as specific visualization browsers to rapidly assess the biological relevance of the dataset. Our approach has been successfully tested on a broad range of datasets that include diverse biological samples and cryo-ET modalities.

Fertility Preservation and Ovarian Hyperstimulation Syndrome Management in Cancer Care: A Pathophysiological Perspective on Gonadotropin-Releasing Hormone Agonists and Antagonists.

This narrative review delves into the evolving landscape of fertility preservation techniques, with a particular focus on their use in patients undergoing oncology treatment that carries a risk of ovarian insufficiency. Advances in established methods such as cryopreservation of oocytes and embryos are highlighted, and the increasing use of gonadotropin-releasing hormone (GnRH) agonists is discussed. The review also addresses the complexities and controversies associated with these approaches, such as the 'flare-up' effect associated with GnRH agonists and the potential of GnRH antagonists to reduce the risk of ovarian hyperstimulation syndrome. Despite advances in fertility preservation, the report highlights the challenges we face, including the need for personalized treatment protocols and the management of associated risks. It calls for continued research and collaboration between healthcare professionals to refine these techniques and ultimately improve reproductive outcomes for patients facing the prospect of fertility-impairing treatment.

Prospective Randomized Controlled Clinical Trial of the Long-Term Effects of Omeprazole on Healthy Dogs.

The use of omeprazole as a preventive treatment for gastrointestinal ulcers in veterinary medicine has been questioned during previous years. The aim of the present study is to assess the long-term effect of omeprazole on cobalamin and serum gastrin levels in healthy dogs. Eighteen healthy dogs were included: 10 in the control group and 8 in the omeprazole group. Three samples were collected: before starting the treatment (T0), 30 days after the start of treatment (T1), and at 60 days (T2). The mean cobalamin value (ng/L) in the control group was 481.4 (±293.70) at T0, 481.4 (±170.21) at T1, and 513.2 (±174.50) at T2. In the omeprazole group, the values were 424.62 (±161.57) at T0, 454.5 (±160.96) at T1, and 414.87 (±127.90) at T2. No statistically significant changes were detected in cobalamin levels between the three-time period in both study groups. These results agree with previous findings in felines but contrast with human medicine studies. The median gastrin values (pg/mL) in the control group were 62.45 [30.17-218.75] at T0, 76.06 [30.67-199.87] at T1, and 63.02 [35.81-176.06] at T2. The median gastrin value in the omeprazole group was 67.59 [55.96-101.60] at T0, 191.77 [75.31-1901.77] at T1, and 128.16 [43.62-1066.46] at T2. Statistically significant differences were detected (p = 0.008), indicating an increase in gastrin levels after initiating treatment with omeprazole. In conclusion, the increased levels of gastrin observed in this population underscore the importance of conducting a comprehensive clinical assessment to identify potential gastrointestinal disorders, particularly in consideration of the usage of omeprazole as a preventive treatment.

Effectiveness and Safety of Non-Invasive Neuromodulation for Vision Restoration: A Systematic Review and Meta-Analysis.

We carried out a systematic review and meta-analysis to determine the effectiveness and safety of non-invasive electrical stimulation (NES) for vision restoration. We systematically searched for randomised controlled trials (RCTs) comparing NES with sham stimulation, for vision restoration between 2000 and 2022 in CENTRAL, MEDLINE, EMBASE, and LILACS. The main outcomes were as follows: visual acuity (VA); detection accuracy; foveal threshold; mean sensitivity as the parameter for the visual field; reading performance; contrast sensitivity (CS); electroencephalogram; quality of life (QoL), and safety. Two reviewers independently selected studies, extracted data, and evaluated the risk of bias using the Cochrane risk of bias 2.0 tool. The certainty in the evidence was determined using the GRADE framework. Protocol registration: CRD42022329342. Thirteen RCTs involving 441 patients with vision impairment indicate that NES may improve VA in the immediate post-intervention period (mean difference [MD] = -0.02 logMAR, 95% confidence intervals [CI] -0.08 to 0.04; low certainty), and probably increases QoL and detection accuracy (MD = 0.08, 95% CI -0.25 to 0.42 and standardised MD [SMD] = 0.09, 95% CI -0.58 to 0.77, respectively; both moderate certainty). NES likely results in little or no difference in mean sensitivity (SMD = -0.03, 95% CI -0.53 to 0.48). Compared with sham stimulation, NES increases the risk of minor adverse effects (risk ratio = 1.24, 95% CI 0.99 to 1.54; moderate certainty). The effect of NES on CS, reading performance, and electroencephalogram was uncertain. Our study suggests that although NES may slightly improve VA, detection accuracy, and QoL, the clinical relevance of these findings remains uncertain. Future research should focus on improving the available evidence's precision and consistency.

Intrauterine insemination: prognostic factors.

OBJECTIVE: To evaluate the impact of possible maternal and paternal prognostic factors and ovarian stimulation protocols on clinical pregnancy and live birth rates in intrauterine insemination (IUI) cycles. METHODS: Retrospective observational study of 341 IUI cycles performed from January 2016 to November 2020 at the Assisted Reproduction Service of the Clinics Hospital of the Ribeirão Preto Medical School, University of São Paulo. Clinical pregnancy and live birth rates and their potential prognostic factors were evaluated. Wilcoxon's non-parametric test was used to compare quantitative variables, and the chi-square test to compare qualitative variables, adopting a significance level of p<0.05. A logistic regression model was performed to verify which exploratory variables are predictive factors for pregnancy outcome. RESULTS: The ovulation induction protocol using gonadotropins plus letrozole (p=0.0097; OR 4.3286, CI 1.3040 - 14.3684) and post-capacitation progressive sperm ≥ 5million/mL (p=0.0253) showed a statistically significant correlation with the live birth rate. Female and male age, etiology of infertility, obesity, multifollicular growth, endometrial thickness ≥ 7 mm, and time between human chorionic gonadotropin administration and IUI performance were not associated with the primary outcomes. In the group of patients with ideal characteristics (women aged< 40 years, BMI < 30 kg/m2, antral follicle count ≥ 5, partner aged< 45 years, and post-capacitation semen with progressive spermatozoa ≥ 5 million/mL), the rate of clinical pregnancy was 14.8%, while that of live birth, 9.9%. CONCLUSIONS: In this study, the ovulation induction protocol with gonadotropins plus letrozole and post-capacitation progressive sperm ≥ 5 million/mL were the only variables that significantly correlated with intrauterine insemination success.

T-cell immune profile in blood of systemic mastocytosis: Association with disease features.

BACKGROUND: Systemic mastocytosis (SM) is a heterogeneous disease characterized by an expansion of KIT-mutated mast cells (MC). KIT-mutated MC display activated features and release MC mediators that might act on the tumour microenvironment and other immune cells. Here, we investigated the distribution of lymphocyte subsets in blood of patients with distinct subtypes of SM and determined its association with other disease features. METHODS: We studied the distribution of TCD4+ and TCD4- cytotoxic cells and their subsets, as well as total NK- and B cells, in blood of 115 SM patients-38 bone marrow mastocytosis (BMM), 67 indolent SM (ISM), 10 aggressive SM (ASM)- and 83 age-matched healthy donors (HD), using spectral flow cytometry and the EuroFlow Immunomonitoring panel, and correlated it with multilineage KITD816V, the alpha-tryptasemia genotype (HαT) and the clinical manifestations of the disease. RESULTS: SM patients showed decreased counts (vs. HD) of TCD4- cytotoxic cells, NK cells and several functional subsets of TCD4+ cells (total Th1, Th2-effector memory, Th22-terminal effector and Th1-like Tregs), together with increased T-follicular-helper and Th1/Th17-like Treg counts, associated with different immune profiles per diagnostic subtype of SM, in multilineal versus MC-restricted KITD816V and in cases with a HαT+ versus HαT- genotype. Unique immune profiles were found among BMM and ISM patients with MC-restricted KITD816V who displayed HαT, anaphylaxis, hymenoptera venom allergy, bone disease, pruritus, flushing and GI symptoms. CONCLUSION: Our results reveal altered T- and NK-cell immune profiles in blood of SM, which vary per disease subtype, the pattern of involvement of haematopoiesis by KITD816V, the HαT genotype and specific clinical manifestations of the disease.

In situ architecture of Opa1-dependent mitochondrial cristae remodeling.

Cristae membrane state plays a central role in regulating mitochondrial function and cellular metabolism. The protein Optic atrophy 1 (Opa1) is an important crista remodeler that exists as two forms in the mitochondrion, a membrane-anchored long form (l-Opa1) and a processed short form (s-Opa1). The mechanisms for how Opa1 influences cristae shape have remained unclear due to lack of native three-dimensional views of cristae. We perform in situ cryo-electron tomography of cryo-focused ion beam milled mouse embryonic fibroblasts with defined Opa1 states to understand how each form of Opa1 influences cristae architecture. In our tomograms, we observe a variety of cristae shapes with distinct trends dependent on s-Opa1:l-Opa1 balance. Increased l-Opa1 levels promote cristae stacking and elongated mitochondria, while increased s-Opa1 levels correlated with irregular cristae packing and round mitochondria shape. Functional assays indicate a role for l-Opa1 in wild-type apoptotic and calcium handling responses, and show a compromised respiratory function under Opa1 imbalance. In summary, we provide three-dimensional visualization of cristae architecture to reveal relationships between mitochondrial ultrastructure and cellular function dependent on Opa1-mediated membrane remodeling.

Clinical impact of the TPSAB1 genotype in mast cell diseases: A REMA study in a cohort of 959 individuals.

BACKGROUND: A close association between hereditary alpha-tryptasemia (HAT) and mast cell (MC) disorders has been previously reported. However, the relationship between HAT and the diagnostic subtypes and clinical features of MC disorders still remains to be established. OBJECTIVE: To determine the prevalence of HAT in healthy donors (HD) vs patients with different diagnostic subtypes of MC activation syndromes (MCAS) and mastocytosis, and its relationship with the clinical behavior of the disease. METHODS: A total of 959 subjects were studied including 346 healthy donors (HD), 464 mastocytosis, and 149 non-clonal MCAS patients. Molecular studies to assess the TPSAB1 genotype were performed, and data on serum baseline tryptase (sBT) and basal MC-mediator release episodes and triggers of anaphylaxis were collected. RESULTS: HAT was detected in 15/346 (4%) HD versus 43/149 (29%) non-clonal MCAS and 84/464 (18%) mastocytosis cases. Among mastocytosis, HAT was more frequently found in patients with MC-restricted KITD816V (21% vs. 10% among multilineage KITD816V patients; p = .008). Overall, median sBT was higher in cases presenting with HAT (28.9 vs. 24.5 ng/mL; p = .008), while no significant differences in sBT were observed among HAT+ mastocytosis patients depending on the presence of 1 vs. ≥2 extra copies of the α-tryptase gene (44.1 vs. 35.2 ng/mL, p > .05). In turn, anaphylaxis was more frequently observed in HAT+ versus HAT- mastocytosis patients (76% vs. 65%; p = .018), while HAT+ and HAT- patients who did not refer anaphylaxis as the presenting symptom (n = 308) showed a similar prevalence of subsequent anaphylaxis (35% vs. 36%, respectively). CONCLUSION: The frequency of HAT in MC disorders varies according to the diagnostic subtype of the disease. HAT does not imply a higher risk (and severity) of anaphylaxis in mastocytosis patients in whom anaphylaxis is not part of the presenting symptoms of the disease.

Risk of ovarian hyperstimulation syndrome in women with malignancies undergoing treatment with long-acting gonadotropin-releasing hormone agonist after controlled ovarian hyperstimulation for fertility preservation: a systematic review.

Background: Fertility preservation is an important quality of life issue for women of reproductive age undergoing gonadotoxic treatment. The possibility of administering an adjuvant long-acting gonadotropin-releasing hormone agonist (GnRHa) with the aim of reducing the number of follicles susceptible to the effects of chemotherapy and thus reducing the risk of ovarian damage is considered in some international society guidelines, particularly in certain cancers such as breast cancer. Nowadays, the administration of long-acting GnRHa after controlled ovarian hyperstimulation (COH) for fertility preservation by cryopreservation of oocytes or embryos is increasingly used. However, cases of ovarian hyperstimulation syndrome (OHSS) have been reported following the use of long-acting GnRHa after COH for fertility preservation, indicating that the potential adverse effects of this treatment need to be further investigated. Objectives: The aim of this systematic review was to comprehensively characterize patients who developed OHSS after treatment with long-acting GnRHa following COH for fertility preservation. Methods: A comprehensive search of major electronic databases through January 2023 was performed. Studies reporting the use of long-acting GnRHa after COH for fertility preservation and the development of OHSS were included. Risk of bias was assessed using a modified version of the Newcastle-Ottawa scale. Results were synthesized qualitatively. Results: Three studies with five patients met the eligibility criteria. The majority of patients were diagnosed with breast cancer and all patients underwent COH for oocyte cryopreservation. OHSS occurred in all patients after administration of long-acting GnRHa. The interval between ovulation induction and administration of long-acting GnRHa thereafter ranged from 3 to 5 days. All patients were treated conservatively and recovered without complications. Conclusion: Current evidence suggests that the use of long-acting GnRHa after COH for fertility preservation may be associated with OHSS. Healthcare providers should thoroughly discuss the benefits and risks of this intervention with their patients before making a decision. Further studies are needed to fully elucidate the causal relationship between long-acting GnRHa and OHSS in this population.

Omega-3 fatty acids and L-carnitine prevent meiotic oocyte damage induced by follicular fluid from infertile women with endometriosis: an experimental study.

OBJECTIVE: To assess whether follicular fluid (FF) from infertile women with endometriosis in advanced stages [moderate/severe (EIII/IV) without or with endometrioma (Endometrioma)] induce more oocyte damages than in early stages (minimal/mild: EI/II); and whether supplementation with L-carnitine (LC) and omega 3 (n3) can prevent these oocyte damages. METHODS: Experimental study using bovine oocytes (obtained of ovaries from slaughterhouse), and human FF (samples were obtained during oocyte recovery for ICSI). Bovine oocytes were submitted to in vitro maturation (IVM) divided into 9 groups: no FF(No-FF), with 1% FF from infertile women without endometriosis (FFC), with EI/II, EIII/IV and Endometrioma, and with (or not) LC+n3 addition. After IVM, oocytes were fluorescently labelled and visualized by confocal microscopy to analyze chromosomes and spindle. RESULTS: FF from endometriosis decreased rate of normal MII (spindle assembly and chromosome alignment) compared to No-FF (87.2%) and FFC (87.2%). FFEIII/IV (80.7%) and FFEndometrioma (69.3%) decreased total MII rate compared to No-FF (91.9%) and FFC (89.2%), and FFEndometrioma had lower total MII rate compared to other groups. LC+n3 increased MII rate in the FFEIII/IV (80.7% vs. 90.8%) and the Endometrioma (69.3% vs. 86.4%), and it prevented damages in spindle and chromosomes in MII oocytes in the FFEI/II group (62.2% vs. 84.5%) and the FFEIII/IV group (70.2% vs. 84.1%). CONCLUSIONS: FF of endometriosis damaged the meiotic spindle of bovine MII oocytes. EIII/IV led to impaired nuclear maturation; FF from women with endometrioma had further negative impact in oocyte maturation. LC+n3 completely prevented the effects of FF from women with endometriosis on oocyte.

Live birth after single euploid frozen embryo transfer in a 39-year-old woman with high-grade mosaic Turner syndrome.

OBJECTIVE: To describe the reproductive and obstetric outcomes of an intracytoplasmic sperm injection cycle with preimplantation genetic testing for aneuploidy in an advanced reproductive-age woman with high-grade mosaic Turner syndrome. METHODS: Case report of a 39-year-old woman diagnosed with mosaic Turner Syndrome 45,X[90]/46,XX[10] karyotype who underwent in vitro fertilization treatment with blastocyst trophectoderm biopsy for preimplantation genetic testing using next-generation sequencing. RESULT(S): Two of the four blastocysts biopsied were euploid. The patient achieved ongoing pregnancy after the first single euploid frozen embryo transfer, followed by the birth of a healthy child. CONCLUSION: Autologous intracytoplasmic sperm injection cycles can be considered in a select group of advanced reproductive-age women diagnosed with high-grade mosaic Turner syndrome.

Sex and age differences in mice models of effort-based decision-making and anergia in depression: the role of dopamine, and cerebral-dopamine-neurotrophic-factor.

Mesolimbic dopamine (DA) regulates vigor in motivated behavior. While previous results have mainly been performed in male rodents, the present studies compared CD1 male and female mice in effort-based decision-making tests of motivation. These tests offered choices between several reinforcers that require different levels of effort (progressive ratio/choice task and 3-choice-T-maze task). Sweet reinforcers were used in both tasks. In the operant tasks, females worked harder as the task required more effort to access a 10% sucrose solution. Although males and females did not differ in preference for 10% vs 3% solutions under free concurrent presentation, females consumed more of the 10% solution when tested alone. The operant task requires a long period of training and changes in the DA system due to age can be mediating long-term changes in effort. Thus, age and sex factors were evaluated in the T-maze task, which requires only a short training period. Both sexes and ages were equally active when habituated to the running wheel (RW), but females consumed more sweet pellets than males, especially at an older age. Both sexes had a strong preference for the RW compared to more sedentary reinforcers in the 3-choice-T-maze test, but older animals spent less time running and ate more than the young ones. The DA-depleting agent tetrabenazine reduced time running in older mice but not in adolescents. Cerebral-dopamine-neurotrophic-factor was reduced in older mice of both sexes compared to adolescent mice. These results emphasize the importance of taking into account differences in sex and age when evaluating willingness to exert effort for specific reinforcers.

Urinary Electrophoretograms Performed by Capillary Electrophoresis: Comparison between Dogs and Cats.

Electrophoresis of urine to evaluate different urinary proteins has been used in recent years in veterinary medicine, as it can be a useful laboratory tool in the early detection of kidney damage. However, urinary capillary electrophoresis (UCE) has not been reported in healthy cats. In healthy dogs, reference intervals have been established and can be compared with pathological samples as these provide an easily interpretable pattern. The electrophoretogram in this study is divided into five fractions (F1-F5) by serum (albumin; alpha1-globulin; alpha2-globulin; beta-globulin; and gamma-globulin). Urine samples from 14 healthy cats were obtained by eco-guided cystocentesis. UCE was run in all samples and compared to 123 dog electrophoretograms from a previously published study. Fraction 2 (alpha1-globulin) was statistically decreased in cats (G1) compared to dogs (G2). Fraction 4 (beta-globulin) was statistically augmented in cats compared to the canine population (G2). Fraction 5 (gamma-globulin) was statistically decreased in cats (G1) compared to dogs (G2). No statistical correlation was found between each cat's serum and urinary fractions. The results of the present study suggest that UCE patterns in cats are similar to the ones described in dogs. UCE can be a non-invasive new diagnostic tool in cats as pathological patterns can be compared to normal ones.

Vértigo posicional paroxístico benigno y enfermedad de Menière: análisis retrospectivo / Benign paroxysmal positional vertigo and Menière's disease: retrospective analysis

Introducción y objetivo: El Vértigo Posicional Paroxístico Benigno (VPPB) es más frecuente dentro del subgrupo de pacientes con Enfermedad de Menière (EM). El presente estudio tiene como objetivo describir las características clínicas tanto del VPPB como de la EM cuando se encuentran asociados. Método: Realizamos un análisis retrospectivo de 22 pacientes con EM diagnosticados de VPPB entre el 1999 y el 2021 en el Complejo Asistencial Universitario de Salamanca. Se recogieron variables clínicas, tanto de las características del VPPB como de la EM. Resultados: En nuestra base de datos, el 66,66 % de los 22 pacientes eran mujeres con una edad media de 59,33 años. El canal semicircular afecto con más frecuencia fue el posterior derecho. En cuanto al VPPB, un 19% se trata de VPPB multicanal, en casi la mitad (47,62%) se tuvieron que realizar más de tres maniobras para solucionarlo y tardó más de un mes en resolverse en más de la mitad (57,14%). Por otro lado, la EM era bilateral en el 19% de los pacientes, con un tiempo de evolución desde el diagnóstico de más de tres años en el 71,42%. Un tercio de los pacientes había presentado más de 10 crisis en los últimos seis meses, y fluctuación en la audición. En base a estos resultados, parece que los pacientes con EM avanzada tienen más probabilidades de presentar VPPB y con peor resultado en su tratamiento. Conclusión: La aparición conjunta del VPPB y la EM podría afectar al pronóstico de ambas patologías por separado. (AU)

Introuction and objective: Benign Paroxysmal Positional Vertigo (BPPV) is more frequent within the subgroup of patients with Menière's Disease (MD). The present study aims to describe the clinical characteristics of both BPPV and MD, when they are associated. Method: We carried out a retrospective analysis of 22 patients with MD diagnosed with BPPV between 1999 and 2021 at the University Assistance Complex of Salamanca. Clinical variables were collected, both from the characteristics of BPPV and MD. Results: In our database, 66.66% of the 22 patients were women with a mean age of 59.33 years. The most frequently affected semicircular canal was the posterior right. Regarding BPPV, 19% are multichannel BPPV, in almost half (47.62%) more than three maneuvers had to be performed to solve it and it took more than a month to resolve it in more than half (57.14%). On the other hand, MD was bilateral in 19% of patients, with a time since diagnosis of more than three years in 71.42%. A third of the patients had presented more than 10 crises in the last six months, and fluctuation in hearing. Based on these results, it appears that patients with advanced MD are more likely to have BPPV and have a worse treatment outcome. Conclusion: The joint appearance of BPPV and MD could affect the prognosis of both pathologies separately. (AU)

Transposon insertion profiling by sequencing (TIPseq) identifies novel LINE-1 insertions in human sperm.

PURPOSE: Long interspersed nuclear element-1 (LINE-1 or L1) comprises 17% of the human genome. Retrotransposons may perturb gene integrity or alter gene expression by altering regulatory regions in the genome. The germline employs a number of mechanisms, including cytosine methylation, to repress retrotransposon transcription throughout most of life. Demethylation during germ cell and early embryo development de-represses retrotransposons. Intriguingly, de novo genetic variation appearing in sperm has been implicated in a number of disorders in offspring, including autism spectrum disorder, schizophrenia, and bipolar disorder. We hypothesize that human sperm exhibit de novo retrotransposition and employ a new sequencing method, single cell transposon insertion profiling by sequencing (scTIPseq) to map them in small amounts of human sperm. METHODS: Cross-sectional case-control study of sperm samples (n=10 men; ages 32-55 years old) from consenting men undergoing IVF at NYU Langone Fertility Center. scTIPseq identified novel LINE-1 insertions in individual sperm and TIPseqHunter, a custom bioinformatics pipeline, compared the architecture of sperm LINE-1 to known LINE-1 insertions from the European database of Human specific LINE-1 (L1Hs) retrotransposon insertions (euL1db). RESULTS: scTIPseq identified 17 novel insertions in sperm. New insertions were mainly intergenic or intronic. Only one sample did not exhibit new insertions. The location or number of novel insertions did not differ by paternal age. CONCLUSION: This study for the first time reports novel LINE-1 insertions in human sperm, demonstrating the feasibility of scTIPseq, and identifies new contributors to genetic diversity in the human germ line.

A pilot study of LINE-1 copy number and telomere length with aging in human sperm.

PURPOSE: Unlike other cells in the body, in sperm, telomere length (TL) increases with age. TL can regulate nearby genes, and the subtelomeric region is rich in retrotransposons. We hypothesized that age-related telomere lengthening in sperm might suppress Long Interspersed Element 1 (LINE-1/L1), the only competent retrotransposon in humans. METHODS: We measured L1 copy number (L1-CN) and sperm telomere length (STL) from young and older men to evaluate the relationship between age, TL and L1-CN. We also evaluated L1-CN and TL in individual sperm to determine whether these variables influence sperm morphology. STL was assayed by Multiplex quantitative polymerase chain reaction method (mmqPCR) and L1-CN by Quantitative polymerase chain reaction (qPCR). RESULTS: We found that STL increased, and L1-CN decreased significantly with paternal age. STL in normal single sperm was significantly higher than in abnormal sperm. L1-CN did not differ between normal and abnormal sperm. Furthermore, morphologically normal sperm have longer telomeres than abnormal sperm. CONCLUSIONS: Elongation of telomeres in the male germline could repress retrotransposition, which tends to increase with cellular aging. More studies in larger cohorts across a wide age span are needed to confirm our conclusions and explore their biological and clinical significance.

Factors Impacting the Use or Rejection of Hearing Aids-A Systematic Review and Meta-Analysis.

PURPOSE: To examine the prevalence of adherence to hearing aids and determine their rejection causes. METHODS: This study was conducted according to the Preferred Reporting terms for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed an electronic search using PubMed, BVS, and Embase. RESULTS: 21 studies that met the inclusion criteria were selected. They analyzed a total of 12,696 individuals. We observed that the most common causes for positive adherence to hearing aid use included having a higher degree of hearing loss, patients being aware of their condition, and requiring the device in their daily life. The most common causes for rejection were the lack of perceived benefits or discomfort with the use of the device. The results from the meta-analysis show a prevalence of patients who used their hearing aid of 0.623 (95% CI 0.531, 0.714). Both groups are highly heterogeneous (I2 = 99.31% in each group, p < 0.05). CONCLUSIONS: A significant proportion of patients (38%) do not use their hearing aid devices. Homogeneous multicenter studies using the same methodology are needed to analyze the causes of rejection of hearing aids.

Climatério e lúpus eritematoso sistêmico / Climacteric and systemic lupus erythematosus

O lúpus eritematoso sistêmico é uma doença crônica, complexa e multifatorial que apresenta manifestações em vários órgãos. O seu acometimento ocorre 10 vezes mais no sexo feminino do que no masculino. É uma doença com uma clínica variada e com graus variados de gravidade, causando fadiga, manifestações cutâneas, como rash malar, fotossensibilidade, queda de cabelo e manifestações musculoesqueléticas, como artralgia, mialgia e atrite. Podem ocorrer flares (crises), que se caracterizam por aumento mensurável na atividade da doença. No climatério, no período da pré-menopausa, o lúpus eritematoso sistêmico ocorre com mais frequência, podendo ocorrer também na pós-menopausa. Algumas doenças são mais frequentes na fase do climatério, e a presença do lúpus pode influenciar na sua evolução, como a doença cardiovascular, osteoporose e tromboembolismo venoso. A terapia hormonal oral determina aumento do risco de tromboembolismo venoso no climatério, e na paciente com lúpus eritematoso sistêmico há aumento dos riscos de flares e de trombose. Em vista disso, a terapia hormonal é recomendada apenas para pacientes com lúpus eritematoso sistêmico estável ou inativo, sem história de síndrome antifosfolípides e com anticorpos antifosfolípides negativa, devendo-se dar preferência para a terapia estrogênica transdérmica, em menor dose e de uso contínuo. Na paciente com lúpus eritematoso sistêmico ativo ou com história de síndrome antifosfolípides ou com anticorpos antifosfolípides positiva, recomenda-se a terapia não hormonal, como os antidepressivos. (AU)

Systemic lupus erythematosus is a chronic, complex, multifactorial disease that manifests in several organs. Its involvement occurs 10 times more in females than in males. It is a disease with a varied clinic and varying degrees of severity, causing fatigue, skin manifestations such as malar rash, photosensitivity, hair loss and musculoskeletal manifestations such as arthralgia, myalgia and arthritis. Flare may occur, which are characterized by measurable increase in disease activity. In the climacteric, in the premenopausal period, systemic lupus erythematosus occurs more frequently, and may also occur in the postmenopausal period. Some diseases are more frequent in the Climacteric phase and the presence of lupus can influence its evolution, such as cardiovascular disease, osteoporosis and venous thromboembolism. Oral hormone therapy determines an increased risk of venous thromboembolism in the climacteric and in patients with systemic lupus erythematosus there is an increased risk of flares and thrombosis. In view of this, hormone therapy is only recommended for patients with stable or inactive systemic lupus erythematosus, without a history of antiphospholipid syndrome and with antiphospholipid antibodies, giving preference to transdermal estrogen therapy, at a lower dose and for continuous use. In patients with active systemic lupus erythematosus or with a history of antiphospholipid syndrome or positive antiphospholipid antibodies, non-hormonal therapy, such as antidepressants, is recommended. (AU)