Inhibin B and antiMüllerian hormone as surrogate markers of fertility in male and female Crohn's disease patients: a case-control study.

Background: Several studies suggest that women with Crohn disease (CD) have reduced fertility due to decreased ovarian reserve, among other causes. On the other hand, male CD patients could have difficulties conceiving. The present study aimed to test the effect of CD on both male and female fertility potential, Sertoli cell function and ovarian reserve, assessed by inhibin-B (IB) plus IB:FSH ratio (IFR) and antiMüllerian hormone (AMH), respectively. Sexual dysfunction (SD) was studied as secondary endpoint. Methods: We performed a cross-sectional, case-control study. Serum IB levels plus IFR were measured in 58 men with CD and compared to 25 age-matched healthy controls (HC). Serum AMH levels were measured in 50 women with CD and in 30 HC matched by age. SD was assessed by means of the International Index of Erectile Function (IIFE-15) in males and the Index of Female Sexual Function (IFSF) in women. Results: A total of 108 CD patients and 55 HC were included. IB serum levels were significantly lower in CD men than in HC (177 ± 58 vs. 234 ± 75 pg./mL, p = 0.001). IFR was also decreased in CD patients compared to HC (58.27 ± 59.5 vs. 91.35 ± 60.04, p = 0.014). Women with CD > 30 years had lower serum AMH levels compared to HC (1.15 ± 0.74 vs. 2.14 ± 1.68 ng/mL, p = 0.033). In addition, CD women >30 years presented a serum AMH < 2 ng/mL more frequently than HC (90% vs. 40%, p = 0.004). The prevalence of SD was significantly higher among both male and female CD patients compared to HC, without association to fertility potential. Age was the only predictor of low ovarian reserve. Conclusion: Testicular Sertoli cell function assessed through serum IB levels and IFR is decreased in CD male patients compared to HC, regardless of age. Age > 30 years is the single independent predictor of reduced ovarian reserve in women with CD. These results should be confirmed in further studies in order to properly counsel patients with CD and desire for offspring.

Mutational landscape of risk variants in comorbid depression and obesity: a next-generation sequencing approach.

Major depression (MD) and obesity are complex genetic disorders that are frequently comorbid. However, the study of both diseases concurrently remains poorly addressed and therefore the underlying genetic mechanisms involved in this comorbidity remain largely unknown. Here we examine the contribution of common and rare variants to this comorbidity through a next-generation sequencing (NGS) approach. Specific genomic regions of interest in MD and obesity were sequenced in a group of 654 individuals from the PISMA-ep epidemiological study. We obtained variants across the entire frequency spectrum and assessed their association with comorbid MD and obesity, both at variant and gene levels. We identified 55 independent common variants and a burden of rare variants in 4 genes (PARK2, FGF21, HIST1H3D and RSRC1) associated with the comorbid phenotype. Follow-up analyses revealed significantly enriched gene-sets associated with biological processes and pathways involved in metabolic dysregulation, hormone signaling and cell cycle regulation. Our results suggest that, while risk variants specific to the comorbid phenotype have been identified, the genes functionally impacted by the risk variants share cell biological processes and signaling pathways with MD and obesity phenotypes separately. To the best of our knowledge, this is the first study involving a targeted sequencing approach toward the study of the comorbid MD and obesity. The framework presented here allowed a deep characterization of the genetics of the co-occurring MD and obesity, revealing insights into the mutational and functional profile that underlies this comorbidity and contributing to a better understanding of the relationship between these two disabling disorders.

Salivary and serum haptoglobin, adenosine deaminase, and immunoglobulin G in growing pigs.

BACKGROUND: Identification of animals in need of medical treatment is important in porcine health management, where analytical samples applicable at farm level could be utilized. Several biomarkers are measurable in saliva, which is less stressful to collect than blood. Saliva sampling is easy to learn and repeatable, making it suitable for monitoring purposes. Previous research suggests that porcine health biomarkers are dependent on production stage and gender, and that combining biomarkers improves diagnostic sensitivity. However, proper monitoring of biomarkers during the complete production cycle has not been studied. We aimed to describe the dynamics of salivary and serum haptoglobin (Hp), adenosine deaminase (ADA), and immunoglobulin G (IgG) in four production stages (suckling, early growing, late growing, finishing), on commercial Finnish pig farms using a total of 117 piglets. The relationship between gender and biomarker dynamics was investigated, as well as the relationships between these biomarkers in saliva and serum. RESULTS: The highest salivary concentrations of Hp, ADA and IgG were measured in suckling piglets. The differences between production stages were generally larger in saliva than for the corresponding serum biomarkers. All correlation coefficients between salivary biomarkers were positive in each production stage and the strength of the correlation varied from 0.245 to 0.762. No similar trend was observed regarding correlation coefficients either between serum biomarkers or between salivary and serum biomarkers. Gender was associated with some biomarker concentrations. CONCLUSIONS: The biomarker dynamics supported previous findings that collection of analytical samples should be conducted in age-matched populations. Positive and even strong relationships between salivary biomarkers indicate the potential to use especially saliva for health monitoring. Our results also suggest the importance of considering gender effects when assessing some salivary or serum biomarkers.

Trends in Targeted Therapy Usage in Inflammatory Bowel Disease: TRENDY Study of ENEIDA.

Markers that allow for the selection of tailored treatments for individual patients with inflammatory bowel diseases (IBD) are yet to be identified. Our aim was to describe trends in real-life treatment usage. For this purpose, patients from the ENEIDA registry who received their first targeted IBD treatment (biologics or tofacitinib) between 2015 and 2021 were included. A subsequent analysis with Machine Learning models was performed. The study included 10,009 patients [71% with Crohn's disease (CD) and 29% with ulcerative colitis (UC)]. In CD, anti-TNF (predominantly adalimumab) were the main agents in the 1st line of treatment (LoT), although their use declined over time. In UC, anti-TNF (mainly infliximab) use was predominant in 1st LoT, remaining stable over time. Ustekinumab and vedolizumab were the most prescribed drugs in 2nd and 3rd LoT in CD and UC, respectively. Overall, the use of biosimilars increased over time. Machine Learning failed to identify a model capable of predicting treatment patterns. In conclusion, drug positioning is different in CD and UC. Anti-TNF were the most used drugs in IBD 1st LoT, being adalimumab predominant in CD and infliximab in UC. Ustekinumab and vedolizumab have gained importance in CD and UC, respectively. The approval of biosimilars had a significant impact on treatment.

The relationship between BDNF and physical activity on depression.

BACKGROUND/OBJECTIVE: Major depressive disorder (MDD) is one of the leading causes of disease burden and disability worldwide. Brain-derived neurotrophic factor (BDNF) seems to have an important role in the molecular mechanisms underlying MDD aetiology, given its implication in regulating neuronal plasticity. There is evidence that physical activity (PA) improves depressive symptoms, with a key role of BDNF in this effect. We aim to perform a systematic review examining the relationship between the BDNF Val66Met polymorphism and the BDNF protein, PA and MDD. METHODS: Both observational and experimental design original articles or systematic reviews were selected, according to the PRISMA statement. RESULTS: Six studies evaluated the Val66Met polymorphism, suggesting a greater impact of physical activity on depression depending on the Val66Met genotype. More discordant findings were observed among the 13 studies assessing BDNF levels with acute or chronic exercise interventions, mainly due to the high heterogeneity found among intervention designs, limited sample size, and potential bias. CONCLUSIONS: Overall, there is cumulative evidence supporting the potential role of BDNF in the interaction between PA and MDD. However, this review highlights the need for further research with more homogeneous and standardised criteria, and pinpoints important confounding factors that must be considered in future studies to provide robust conclusions.

Toward the elimination of hepatitis B: networking to promote the prevention of vertical transmission of hepatitis B virus through population-based interventions and multidisciplinary groups in Africa.

The WHO African Region had 81 million people with chronic hepatitis B in 2019, which remains a silent killer. Hepatitis B virus (HBV), hepatitis delta virus (HDV), and HIV can be transmitted from the mother to child. If the HBV infection is acquired at infancy, it may lead to chronic hepatitis B in 90% of the cases. WHO reports that 6.4 million children under 5 years live with chronic hepatitis B infection worldwide. The prevention of mother-to-child transmission (PMTCT) of HBV is therefore critical in the global elimination strategy of viral hepatitis as we take lessons from PMTCT of HIV programs in Africa. We sought to create a network of multidisciplinary professional and civil society volunteers with the vision to promote cost-effective, country-driven initiatives to prevent the MTCT of HBV in Africa. In 2018, the Mother-Infant Cohort Hepatitis B Network (MICHep B Network) with members from Cameroon, Zimbabwe, and the United Kingdom and later from Chad, Gabon, and Central African Republic was created. The long-term objectives of the network are to organize capacity-building and networking workshops, create awareness among pregnant women, their partners, and the community, promote the operational research on MTCT of HBV, and extend the network activities to other African countries. The Network organized in Cameroon, two "Knowledge, Attitude and Practice" (KAP) surveys, one in-depth interview of 45 health care workers which revealed a high acceptability of the hepatitis B vaccine by families, two in-person workshops in 2018 and 2019, and one virtual in 2021 with over 190 participants, as well as two workshops on grant writing, bioethics, and biostatistics of 30 postgraduate students. Two HBV seroprevalence studies in pregnant women were conducted in Cameroon and Zimbabwe, in which a prevalence of 5.8% and 2.7%, respectively, was reported. The results and recommendations from the MICHep B Network activities could be implemented in countries of the MICHep B Network and beyond, with the goal of providing free birth dose vaccine against hepatitis B in Africa.

Enfoques extras disciplinarios para aproximar la brecha teoría y práctica: Pierre Bourdieu y la interseccionalidad / Abordagens extra-disciplinares para colmatar o fosso entre a teoria e a prática: Pierre Bourdieu e a interseccionalidade / Extra-disciplinary approaches to bridging the theory-practice gap: Pierre Bourdieu and intersectionality

En esta editorial el autor reflexiona acerca de la dicotomía teoría/práctica y como la integración de teorías transdisciplinarias pueden contribuir a acercar posturas. Para ello comenta la teoría de la práctica desarrollada por Bourdieu y la interseccionalidad aportando un ejemplo de como su interconexión puede mejorar tanto la teoría como la práctica de la enfermería y por tanto contribuyendo a su vertebración y epistemología.(AU)

In this editorial the author reflects on the theory/practicedichotomy and how the integration of transdisciplinarytheories can help to bring positions closer together. To doso, he discusses the theory of practice developed by Bourdieuand intersectionality, providing an example of how theirinterconnection can improve both the theory and practice ofnursing and thus contribute to its structuring and epistemology.(AU)

Neste editorial o autor reflecte sobre a dicotomia teoria/práticae como a integração de teorias transdisciplinares pode ajudar aaproximar posições. Para isso, discute a teoria da prática desenvolvidapor Bourdieu e a interseccionalidade, exemplificando como a suainterligação pode melhorar a teoria e a prática da enfermageme, assim, contribuir para a sua estruturação e epistemologia.(AU)

Barbed versus conventional suture in elective posterior spine surgery.

PURPOSE: Barbed sutures are tissue control devices that can reduce operating room time and costs. We analyzed the utility of barbed sutures in posterior spinal surgery in order to prove non-inferiority to conventional methods for wound closure. METHODS: A cohort of patients undergoing elective posterior spinal surgery in which barbed (prospective) versus conventional sutures (retrospective) were used was analyzed. The primary endpoint was the occurrence of wound healing complications or the need for surgical revision. Secondary endpoints included postoperative stay, readmission rate, and duration and cost of wound closure. RESULT: A total of 483 patients participated in the study, 183 in the Barbed group and 300 in the Conventional group. Wound dehiscence or seroma occurred in 3.8% and 2.7% of the Barbed and Conventional groups, respectively (p = 0.6588). Both superficial (1.6% versus 4.0%, P = 0.2378) and deep infections (2.7% versus 4.7%, p = 0.4124) occurred similarly in both groups. Overall, the rate of re-intervention due to wound healing problems was also similar (4.9% versus 5.3%, p = 0.9906), as well as, total median hospital stay, postoperative stay and 30-day re-admission rates. The average duration of wound closure (1.66 versus 4.16 min per level operated, p < 0.0001) strongly favored the Barbed group. The mean cost of wound closure per patient was higher in the Barbed group (43.23 € versus 22.67 €, p < 0.0001). CONCLUSIONS: In elective posterior spinal procedures, the use of barbed sutures significantly reduced the duration of wound closure. The wound healing process was not hindered and the added cost related to the suture material was small.

Percutaneous Gastrostomies: Associated Complications in PUSH vs. PULL Techniques over 12 Years in a Referral Centre.

Objectives: To compare complications associated with percutaneous gastrostomies performed using PUSH and PULL techniques, whether endoscopic (PEG) or radiological (PRG), in a tertiary-level hospital. Methods: This was a prospective observational study. Adult patients who underwent percutaneous PULL or PUSH gastrostomy using PEG or PRG techniques at the Virgen del Rocio University Hospital and subsequently followed up in the Nutrition Unit between 2009-2020 were included. X2 tests or Fisher's test were used for the comparison of proportions when necessary. Univariate analysis was conducted to study risk factors for PRG-associated complications. Results: n = 423 (PULL = 181; PUSH = 242). The PULL technique was associated with a higher percentage of total complications (37.6% vs. 23.8%; p = 0.005), exudate (18.2% vs. 11.2%; p = 0.039), and irritation (3.3% vs. 0%; p = 0.006). In the total sample, there were 5 (1.1%) cases of peritonitis, 3 (0.7%) gastrocolic fistulas, and 1 (0.2%) death due to complications associated with gastrostomy. Gender, age, and different indications were not risk factors for a higher number of complications. The most common indications were neurological diseases (35.9%), head and neck cancer (29%), and amyotrophic lateral sclerosis (17.2%). Conclusions: The PULL technique was associated with more total complications than the PUSH technique, but both were shown to be safe techniques, as the majority of complications were minor.

Effectiveness and safety of azathioprine for inflammatory pouch disorders: results from the RESERVO study of GETECCU.

Background: The usefulness of thiopurines has been poorly explored in pouchitis and other pouch disorders. Objective: To evaluate the effectiveness and safety of azathioprine as maintenance therapy in inflammatory pouch disorders. Design: This was a retrospective and multicentre study. Methods: We included patients diagnosed with inflammatory pouch disorders treated with azathioprine in monotherapy. Effectiveness was evaluated at 1 year and in the long term based on normalization of stool frequency, absence of pain, faecal urgency or fistula discharge (clinical remission), or any improvement in these symptoms (clinical response). Endoscopic response was evaluated using the Pouchitis Disease Activity Index (PDAI). Results: In all, 63 patients were included [54% males; median age, 49 (28-77) years]. The therapy was used to treat pouchitis (n = 37) or Crohn's disease of the pouch (n = 26). The rate of clinical response, remission and non-response at 12 months were 52%, 30% and 18%, respectively. After a median follow-up of 23 months (interquartile range 11-55), 19 patients (30%) were in clinical remission, and 45 (66%) stopped therapy. Endoscopic changes were evaluated in 19 cases. PDAI score decreased from 3 (range 2-4) to 1 (range 0-3). In all, 21 patients (33%) presented adverse events and 16 (25%) needed to stop therapy. Conclusion: Azathioprine may be effective in the long term for the treatment of inflammatory pouch disorders and could be included as a therapeutic option.

Evaluation of genetic variants associated with the risk of thiopurine-related pancreatitis: a case control study from ENEIDA registry.

BACKGROUND: Risk factors for developing pancreatitis due to thiopurines in patients with inflammatory bowel disease (IBD) are not clearly identified. AIM: Our aim was to evaluate the predictive pharmacogenetic risk of pancreatitis in IBD patients treated with thiopurines. METHODS: We conducted an observational pharmacogenetic study of acute pancreatitis events in a cohort study of IBD patients treated with thiopurines from the prospectively maintained ENEIDA registry biobank of GETECCU. Samples were obtained and the CASR, CEL, CFTR, CDLN2, CTRC, SPINK1, CPA1, and PRSS1 genes, selected based on their known association with pancreatitis, were fully sequenced. RESULTS: Ninety-five cases and 105 controls were enrolled, 57% were women. Median age at pancreatitis diagnosis was 39 years. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes, nor a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes; one of them was in the CDLN gene in a single patient with pancreatitis, and 3 in the CPA1 gene in 5 controls. After the analysis of the variants detected, no significant differences were observed between cases and controls. CONCLUSION: In patients with IBD, genes known to cause pancreatitis seem not to be involved in thiopurine-related pancreatitis onset.

Equity, diversity, and inclusion in the Multinational Association for Supportive Care in Cancer: a global membership survey.

Equity, diversity, and inclusion (EDI) are essential for healthcare organizations since they allow for the development of programs and initiatives that bring together diverse perspectives and knowledge. Global multidisciplinary organizations, such as the Multinational Association for Supportive Care in Cancer (MASCC), need to understand the perspective of their members regarding EDI to identify opportunities to enhance diversity and inclusiveness and to better meet the needs of members from different backgrounds and resources. The MASCC Health Disparities Committee designed a survey to identify issues related to disparities faced by MASCC members when providing supportive care to patients with cancer and to examine the EDI landscape within the organization. Here, we report results related to EDI initiatives within the organization. Two-hundred and eighteen MASCC members responded to the survey (response rate 10.2%). The results indicated that respondents were generally satisfied with how MASCC manages leadership, membership, and organization-related EDI issues. Opportunities for improvement noted by respondents included developing strategies to foster a more diverse membership, improving communication regarding diversity in the organization, and increasing EDI content in educational sessions and publications. The results of this survey represent the first attempt at understanding how to improve EDI within MASCC and will be utilized to guide further initiatives and programs.

Characterization of Antibiotic-Resistance Antarctic Pseudomonas That Produce Bacteriocin-like Compounds.

In this study, bacterial isolates C1-4-7, D2-4-6, and M1-4-11 from Antarctic soil were phenotypically and genotypically characterized, and their antibacterial spectrum and that of cell-free culture supernatant were investigated. Finally, the effect of temperature and culture medium on the production of antimicrobial compounds was investigated. The three bacteria were identified as different strains of the genus Pseudomonas. The three bacteria were multi-drug resistant to antibiotics. They exhibited different patterns of growth inhibition of pathogenic bacteria. M1-4-11 was remarkable for inhibiting the entire set of pathogenic bacteria tested. All three bacteria demonstrated optimal production of antimicrobial compounds at 15 °C and 18 °C. Among the culture media studied, Nutrient broth would be the most suitable to promote the production of antimicrobial compounds. The thermostability exhibited by the antimicrobial molecules secreted, their size of less than 10 kDa, and their protein nature would indicate that these molecules are bacteriocin-like compounds.

Familial bilateral macronodular adrenal hyperplasia due to a novel ARMC 5 germline mutation: Clinical status and possible association with other neoplasms.

INTRODUCTION/OBJECTIVES: Mutations in the ARMC5 (armadillo repeat containing 5, OMIM 615549) gene, a putative tumor suppressor gene, have recently been identified as a common cause of sporadic and familial bilateral macronodular adrenal hyperplasia (BMAH). Familial BMAH is thought to be caused by two mutations, one germline and the other somatic, as suggested by the 2-hit theory. The objective is to describe a new mutation and develop its clinical characteristics and implications. METHODS, RESULTS AND CONCLUSIONS: We present an affected family with 11 members carrying a novel mutation of the ARMC5 gene (NM_001288767.1): c.2162T>C p. (Leu721Pro). Two of the carriers developed clinical Cushing's syndrome (CS), two mild autonomous cortisol secretion (MACS) and one presented with autonomous cortisol secretion (ACS). Four patients developed other tumors, three of whom died from this cause. It is not known whether these tumors could be related to the described mutation.

Difficulties of gender affirming treatment in trans women with BRCA1+ mutation: A case report.

Gender affirming treatment in transgender women is based on a combination of antiandrogens and estrogens, with the latter maintained over the long term. When prescribing these treatments, we must consider the possibility of developing estrogen-dependent breast cancer. In transgender women, a breast cancer incidence of 4.1 per 100,000 has been estimated, which would increase the risk by 46% in relation to cisgender men but decrease it by 70% in relation to cisgender women. It is known that certain gene mutations such as BRCA1 imply an increased risk of breast cancer, but at present the risk in transgender women with BRCA1 treated with estrogens is not well established. We present the case of a transgender woman with a family history of breast cancer and BRCA1 mutation and the therapeutic decisions made in a multidisciplinary team. Following this case, we review and discuss the published literature.

The horizontal ladder test (HLT) protocol: a novel, optimized, and reliable means of assessing motor coordination in Sus scrofa domesticus.

Pigs can be an important model for preclinical biological research, including neurological diseases such as Alcohol Use Disorder. Such research often involves longitudinal assessment of changes in motor coordination as the disease or disorder progresses. Current motor coordination tests in pigs are derived from behavioral assessments in rodents and lack critical aspects of face and construct validity. While such tests may permit for the comparison of experimental results to rodents, a lack of validation studies of such tests in the pig itself may preclude the drawing of meaningful conclusions. To address this knowledge gap, an apparatus modeled after a horizontally placed ladder and where the height of the rungs could be adjusted was developed. The protocol that was employed within the apparatus mimicked the walk and turn test of the human standardized field sobriety test. Here, five Sinclair miniature pigs were trained to cross the horizontally placed ladder, starting at a rung height of six inches and decreasing to three inches in one-inch increments. It was demonstrated that pigs can reliably learn to cross the ladder, with few errors, under baseline/unimpaired conditions. These animals were then involved in a voluntary consumption of ethanol study where animals were longitudinally evaluated for motor coordination changes at baseline, 2.5, 5, 7.5, and 10% ethanol concentrations subsequently to consuming ethanol. Consistent with our predictions, relative to baseline performance, motor incoordination increased as voluntary consumption of escalating concentrations of ethanol increased. Together these data highlight that the horizontal ladder test (HLT) test protocol is a novel, optimized and reliable test for evaluating motor coordination as well as changes in motor coordination in pigs.

Bridging the gap: Experimental evidence on information provision and health insurance choices.

Previous research has shown that individuals do not always make rational decisions when selecting their health insurance, for example, due to the existence of information frictions or mental gaps. We study the effect of specific types of information provision for decision support on health plan choices and test their potential to improve decision quality by implementing a randomized laboratory experiment. We provide personalized and generic aids, differentiate between numerical and visual decision support, and provide one or two optional formats of personalized information. We find that generic aids have no effect on health plan choices while personalized information leads to better choices as measured by several indicators of decision quality. The largest effects were observed for those who "opted in" to visualize personalized information, with immediate and lasting improvements in health insurance decisions. By reducing information frictions, our results suggest that accessible and easy-to-use tools can positively impact health insurance navigation, improve decision-making, and reduce switching costs.

A Qualitative Study Exploring Barriers to Colorectal Cancer Screening among Firefighters.

OBJECTIVE: Firefighters are at increased risk of colorectal cancer (CRC), yet rates of CRC screening are low among this occupational group. This study examines perceived risks, barriers, and facilitators to CRC screening. METHODS: Three semi-structured focus group discussions were conducted by investigators in Tucson, AZ. Thematic analysis was used to identify patterns and themes in the data. RESULTS: Three groups of firefighters (8 male (57%); 6 female (43%) mean age 50.4 (SD = 12.2) years) voluntarily participated in the CRC discussions. Four major themes were examined: (1) perceptions of risk for CRC, (2) barriers to cancer screening, (3) facilitators to getting cancer screening, and (4) misinformation about CRC and screening. CONCLUSIONS: Findings indicate unique perceptions, attitudes, and beliefs among firefighters. Results from this study will inform the adaptation of a tailored CRC screening intervention for firefighters.

General-purpose programmable photonic processor for advanced radiofrequency applications.

A general-purpose photonic processor can be built integrating a silicon photonic programmable core in a technology stack comprising an electronic monitoring and controlling layer and a software layer for resource control and programming. This processor can leverage the unique properties of photonics in terms of ultra-high bandwidth, high-speed operation, and low power consumption while operating in a complementary and synergistic way with electronic processors. These features are key in applications such as next-generation 5/6 G wireless systems where reconfigurable filtering, frequency conversion, arbitrary waveform generation, and beamforming are currently provided by microwave photonic subsystems that cannot be scaled down. Here we report the first general-purpose programmable processor with the remarkable capability to implement all the required basic functionalities of a microwave photonic system by suitable programming of its resources. The processor is fabricated in silicon photonics and incorporates the full photonic/electronic and software stack.