Global Practice Patterns in the Evaluation of Non-Obstructive Azoospermia: Results of a World-Wide Survey and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. MATERIALS AND METHODS: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations. RESULTS: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. CONCLUSIONS: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.

Global Practice Patterns and Variations in the Medical and Surgical Management of Non-Obstructive Azoospermia: Results of a World-Wide Survey, Guidelines and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA. MATERIALS AND METHODS: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process. RESULTS: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit. CONCLUSIONS: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines.

Multizonal observational study conducted by clinical practitioners on Repatha® use in patients with hyperlipidemia (ZERBINI): Colombian results / Estudio Observacional Multizonal realizado por Médicos Clínicos sobre el Uso de Repatha® en Pacientes con Hiperlipidemia (ZERBINI): resultados colombianos

Background Cardiovascular disease (CVD) represents the primary cause of death and disability globally, with elevated cholesterol as one of the leading risk factors for CVD. We describe the clinical characteristics, treatment patterns, and effectiveness of evolocumab in treating hyperlipidemia. Methods Observational study conducted through a chart review of patients with hyperlipidemia receiving evolocumab as part of clinical management in Colombia. Results This study included 115 patients treated with evolocumab. A total of 101 patients (87.8%) had a history of CVD, 13 (11.3%) familial hypercholesterolemia (FH), and 23 (20%) type 2 diabetes. Thirty-nine patients reported intolerance to any statin (33.9%). The median value of LDL-C before initiation of evolocumab was 147mg/dL (IQR: 122.5–183.7mg/dL). Within the first 3 months of treatment, LDL-C value dropped to a median value of 53mg/dL (IQR: 34.0–95.5mg/dL), showing a reduction of 63.9%. The median LDL-C values remained below 45mg/dL until the end of follow-up. Among the patients with available data, up to 61% achieved an LDL-C level below 55mg/dL at the 10–12-month follow-up. A total of 72% of patients were persistent with treatment. Safety results showed a low frequency of hospitalizations (≤2%) and treatment-emergent adverse drug reactions (5.2%). No serious adverse events were reported. Conclusions Evolocumab was associated with reductions in LDL-C levels, with a relative decrease of 63.9% within the first 3 months of treatment. Low rates of interruptions due to adverse events and adequate medication persistence was reported. (AU)

Antecedentes Las enfermedades cardiovasculares (ECV) representan la principal causa de muerte y discapacidad en todo el mundo, siendo el colesterol elevado uno de los principales factores de riesgo de ECV. El presente estudio describe las características clínicas, patrones de tratamiento y la efectividad de evolocumab en el tratamiento de la hiperlipidemia. Métodos Estudio observacional de revisión de historias clínicas de pacientes con hiperlipidemia que reciben evolocumab como parte del manejo clínico en Colombia. Resultados Se incluyeron 115 pacientes tratados con evolocumab. Un total de 101 pacientes (87,8%) presentaron antecedentes de ECV, 13 (11,3%) de hipercolesterolemia familiar y 23 (20%) de diabetes tipo 2. De los pacientes estudiados, 39% declararon intolerancia a alguna estatina (33,9%). La mediana de C-LDL antes del inicio de evolocumab fue de 147mg/dL (IQR: 122,5-183,7mg/dL). En los primeros tres meses de tratamiento, el valor de C-LDL descendió a 53mg/dL (IQR: 34,0-95,5mg/dL), siendo una reducción de 63,9%. La mediana de C-LDL se mantuvo por debajo de 45mg/dL hasta el final del seguimiento. Entre los pacientes con datos disponibles, hasta 61% alcanzó un nivel de LDL-C inferior a 55mg/dL en el seguimiento de 10-12 meses. De los pacientes analizados, 72% fue persistente al tratamiento. Los resultados de seguridad mostraron una baja frecuencia de hospitalizaciones (≤2%) y de reacciones adversas relacionadas al tratamiento (5,2%). No se notificaron acontecimientos adversos graves. Conclusiones Evolocumab se asoció con reducciones en los niveles de C-LDL, con una disminución relativa de 63,9% en los primeros tres meses de tratamiento. Se reportaron bajas tasas de interrupciones por eventos adversos y adecuada persistencia a la medicación. (AU)

Ulcerative colitis and pyoderma gangrenosum refractory to treatment successfully managed with pentoxifylline: a case report.

Introduction and importance: Pyoderma gangrenosum is an unusual inflammatory pathology, with neutrophilic dermatosis, of unknown etiology. It is associated with diseases such as bowel disease. Generally, it is treated with anti-inflammatory drugs, corticosteroids, immunosuppressants, and antibodies against tumor necrosis factor, but relapse and adverse effects are persistent. Pentoxifylline is a drug with immunoregulatory and anti-inflammatory properties. Case presentation: A 47-year-old male with a diagnosis of ulcerative colitis initially managed favorably for 7 years with mesalazine. At 3 years of treatment, he presented a sudden ulcer that affected skin and subcutaneous tissue (13×10 cm) in the lower right limb. During the last 2 years, he was treated with mesalazine and infliximab with partial results and permanent relapses. Therefore, pentoxifylline was added to his treatment. Clinical discussion: The justification for the addition of pentoxifylline is mainly its action as an inhibitor of Nuclear Factor-kappa Beta (NF-κB) transcription, which stimulates the expression of proinflammatory interleukin genes such as IL-1, IL-6, IL- 8, and TNF-α and showing immunoregulatory and antioxidant activities. Conclusion: With pentoxifylline, this lesion healed at 6 weeks without relapses after 2 years.

Does Varicocele Repair Improve Conventional Semen Parameters? A Meta-Analytic Study of Before-After Data.

PURPOSE: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles. MATERIALS AND METHODS: The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intra-person before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies). RESULTS: Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129-0.278; p<0.001; I²=83.62%, Egger's p=0.3329; sperm concentration: SMD 1.590, 95% CI: 1.474-1.706; p<0.001; I²=97.86%, Egger's p<0.0001; total sperm count: SMD 1.824, 95% CI: 1.526-2.121; p<0.001; I²=97.88%, Egger's p=0.0063; total motile sperm count: SMD 1.643, 95% CI: 1.318-1.968; p<0.001; I²=98.65%, Egger's p=0.0003; progressive sperm motility: SMD 1.845, 95% CI: 1.537%-2.153%; p<0.001; I²=98.97%, Egger's p<0.0001; total sperm motility: SMD 1.613, 95% CI 1.467%-1.759%; p<0.001; l2=97.98%, Egger's p<0.001; sperm morphology: SMD 1.066, 95% CI 0.992%-1.211%; p<0.001; I²=97.87%, Egger's p=0.1864. CONCLUSIONS: The current meta-analysis is the largest to date using paired analysis on varicocele patients. In the current meta-analysis, almost all conventional semen parameters improved significantly following varicocele repair in infertile patients with clinical varicocele.

Multizonal observational study conducted by clinical practitioners on Repatha® use in patients with hyperlipidemia (ZERBINI): Colombian results.

BACKGROUND: Cardiovascular disease (CVD) represents the primary cause of death and disability globally, with elevated cholesterol as one of the leading risk factors for CVD. We describe the clinical characteristics, treatment patterns, and effectiveness of evolocumab in treating hyperlipidemia. METHODS: Observational study conducted through a chart review of patients with hyperlipidemia receiving evolocumab as part of clinical management in Colombia. RESULTS: This study included 115 patients treated with evolocumab. A total of 101 patients (87.8%) had a history of CVD, 13 (11.3%) familial hypercholesterolemia (FH), and 23 (20%) type 2 diabetes. Thirty-nine patients reported intolerance to any statin (33.9%). The median value of LDL-C before initiation of evolocumab was 147mg/dL (IQR: 122.5-183.7mg/dL). Within the first 3 months of treatment, LDL-C value dropped to a median value of 53mg/dL (IQR: 34.0-95.5mg/dL), showing a reduction of 63.9%. The median LDL-C values remained below 45mg/dL until the end of follow-up. Among the patients with available data, up to 61% achieved an LDL-C level below 55mg/dL at the 10-12-month follow-up. A total of 72% of patients were persistent with treatment. Safety results showed a low frequency of hospitalizations (≤2%) and treatment-emergent adverse drug reactions (5.2%). No serious adverse events were reported. CONCLUSIONS: Evolocumab was associated with reductions in LDL-C levels, with a relative decrease of 63.9% within the first 3 months of treatment. Low rates of interruptions due to adverse events and adequate medication persistence was reported.

Análisis del programa de apoyo al paciente de evolocumab (Repatha®) para pacientes con enfermedades cardiovasculares en Colombia / Analysis of the evolocumab (Repatha®) patient support program for patients with cardiovascular disease in Colombia

Antecedentes: Las enfermedades cardiovasculares son la principal causa de muerte a nivel mundial. El objetivo es describir las características demográficas, los patrones de tratamiento, cumplimiento terapéutico y continuidad del tratamiento y explorar las variables relacionadas con la falta de adherencia de los pacientes inscritos en un programa de apoyo al paciente (PSP, por sus siglas en inglés) cardiovascular para al tratamiento con evolocumab en Colombia. Métodos: Estudio observacional-retrospectivo del registro de datos de los pacientes que ingresaron al programa PSP de evolocumab. Resultados: El análisis incluyó a 930 pacientes inscritos en el PSP (2017-2021). La edad media fue de 65,1 años (DE±1,1) y el 49,1% eran mujeres. La tasa media de cumplimiento del tratamiento con evolocumab fue del 70,5% (DE±21,8). Un total de 367 pacientes (40,5%) reportaron una tasa de cumplimiento superior al 80%. El análisis de continuidad incluyó a 739 pacientes (81,5%); el 87,8% de estos pacientes fueron considerados persistentes en el tratamiento. Un total de 871 pacientes (93,7%) reportaron al menos un evento adverso durante el período de seguimiento (en su mayoría no graves). Conclusión: Este es el primer estudio de la vida real sobre el tratamiento para la dislipidemia en un programa de apoyo a pacientes en Colombia. La adherencia encontrada fue superior al 70%, cifra similar a los hallazgos de otros estudios de vida real. Entre las causas del bajo cumplimiento se destacan las barreras administrativas y médicas para la suspensión o abandono del tratamiento con evolocumab. (AU)

Background: Cardiovascular diseases are considered the leading cause of death globally. This study describes the demographic characteristics, treatment patterns, self-reported compliance and persistence, and to explore variables related to non-adherence of patients enrolled in the cardiovascular patient support program (PSP) for evolocumab treatment in Colombia. Methods: This retrospective observational of the data registry of patients who entered the evolocumab PSP program. Results: The analysis included 930 patients enrolled in the PSP (2017-2021). Mean age was 65.1 (SD±13.1) and49.1% patients were female. The mean compliance rate to evolocumab treatment was 70.5% (SD±21.8). A total of 367 patients (40.5%) reported compliance higher than 80%. Persistence analysis included 739 patients (81.5%) where 87.8% of these patients were considered persistent to treatment. A total of 871 patients (93.7%) reported the occurrence of at least one adverse event during the follow-up period (mostly non-serious). Conclusion: This is the first real-life study describing patient characteristics, compliance and continuity of treatment for dyslipidemia in a patient support program in Colombia. The overall adherence found was higher than 70%; similar to findings reported in other real-life studies with iPCSK9. However, the reasons for low compliance were different, highlighting the high number of administrative and medical reasons for suspension or abandonment of treatment with evolocumab. (AU)

[Use of implants to treat male urinary incontinence]. / Einsatz von Implantaten zur Versorgung der männlichen Harninkontinenz.

Treatments for benign and malignant pathologies of the prostate can compromise urine control. Urinary incontinence (UI) affects the quality of life of patients and limits their ability to carry out usual activities. The degree of impact of UI is variable and the associated discomforts make patients seek treatment for it. At the center of the management of urinary incontinence in men are surgical interventions that seek to replace the affected sphincter function through implants. The artificial urinary sphincter since its development in the 1970s has been considered the standard of treatment for UI in men. More recently artificial sphincter and slings have been shown to be effective in a selected group of incontinent men. The goals of surgical treatment of incontinence include the preservation of bladder function, the ability to improve the strength of the urinary sphincter, and to reduce or eliminate urine leakage, and thereby improve the quality of life. The aim of the article is to present various implants for the correction of male urinary incontinence.

Intestinal Obstruction Secondary to Gallstone Ileus in a Patient with Cholangitis: Case Report

Gallstone ileus manifests as intestinal obstruction. It occurs due to the passage of a stone and its subsequent lodging in the lumen of the digestive tract. The diagnosis is confirmed by imaging; the gold standard is abdominal tomography. Management is based on the extraction of the intraluminal calculus in one or more surgical times, depending on the patient's condition. We present the case of a patient with multiple comorbidities who showed a picture of cholangitis complicated by gallstone ileus and successfully treated with enterolithotomy. Surgical management is controversial since the optimal approach for these patients has not been established.

El íleo biliar se manifiesta como una obstrucción intestinal, se presenta por el paso de un lito y su posterior alojamiento en el lumen del tubo digestivo. El diagnóstico se confirma mediante imagenología, el patrón de oro es la tomografía abdominal. El manejo se fundamenta en la extracción del cálculo intraluminal en uno o más tiempos quirúrgicos, según el estado del paciente. Se presenta el caso de un paciente con múltiples comorbilidades, que debuta con un cuadro de colangitis complicada por íleo biliar, tratado exitosamente con enterolitotomía. El manejo quirúrgico es controversial, ya que no se ha establecido el abordaje óptimo para estos pacientes.

[Psychosocial consequences of urinary incontinence - tabooed and undertreated: a systematic review]. / Psychosoziale Folgen der Harninkontinenz ­ tabuisiert und unterversorgt ­ eine systematische Übersichtsarbeit.

BACKGROUND: Urinary incontinence is a significant health problem that can affect both women and men of all ages. It is not a life-threatening condition, but symptoms can have a strong impact on the physical, psychological and social well-being of those affected. Existing literature mainly reports on incontinent patients over 65 years of age. Studies about stress and effects of incontinence in younger patients are limited. Incontinence is a social taboo subject, with few sufferers seeking professional help for reasons of shame. Some incontinent individuals seek support when symptoms worsen and further reduce their quality of life. This study aims to explain which psychosocial stresses and effects of urinary incontinence in adults are described in the literature and how those affected experience these. METHODS: A systematic literature search was performed for the years 2007 to 2022 in the databases CINAHL, Cochrane Database of Systematic Reviews via OvidSP, PsycINFO via OvidSP and PubMed. In addition to the research in the databases, a hand search was carried out on the internet and via the reference lists of the included and critically evaluated articles. RESULTS: Incontinence affects the entire life of those affected. Incontinent patients suffer from low self-esteem and shame. They reduce physical activities, have fewer social contacts and experience problems in working life. The condition often leads to impairments in partnership and sexuality. Younger patients have a higher level of suffering than older patients. SUMMARY: In order to contribute to removing the taboo on urinary incontinence, health professionals should be made aware of the living situation of incontinent patients. Patient education is given high priority and strategies need to be developed to help those affected to cope.

Analysis of the evolocumab (Repatha®) patient support program for patients with cardiovascular disease in Colombia. / Análisis del programa de apoyo al paciente de evolocumab (Repatha®) para pacientes con enfermedades cardiovasculares en Colombia.

BACKGROUND: Cardiovascular diseases are considered the leading cause of death globally. This study describes the demographic characteristics, treatment patterns, self-reported compliance and persistence, and to explore variables related to non-adherence of patients enrolled in the cardiovascular patient support program (PSP) for evolocumab treatment in Colombia. METHODS: This retrospective observational of the data registry of patients who entered the evolocumab PSP program. RESULTS: The analysis included 930 patients enrolled in the PSP (2017-2021). Mean age was 65.1 (SD±13.1) and49.1% patients were female. The mean compliance rate to evolocumab treatment was 70.5% (SD±21.8). A total of 367 patients (40.5%) reported compliance higher than 80%. Persistence analysis included 739 patients (81.5%) where 87.8% of these patients were considered persistent to treatment. A total of 871 patients (93.7%) reported the occurrence of at least one adverse event during the follow-up period (mostly non-serious). CONCLUSION: This is the first real-life study describing patient characteristics, compliance and continuity of treatment for dyslipidemia in a patient support program in Colombia. The overall adherence found was higher than 70%; similar to findings reported in other real-life studies with iPCSK9. However, the reasons for low compliance were different, highlighting the high number of administrative and medical reasons for suspension or abandonment of treatment with evolocumab.

N-BAR and F-BAR proteins-endophilin-A3 and PSTPIP1-control clathrin-independent endocytosis of L1CAM.

Recent advances in the field demonstrate the high diversity and complexity of endocytic pathways. In the current study, we focus on the endocytosis of L1CAM. This glycoprotein plays a major role in the development of the nervous system, and is involved in cancer development and is associated with metastases and poor prognosis. Two L1CAM isoforms are subject to endocytosis: isoform 1, described as a clathrin-mediated cargo; isoform 2, whose endocytosis has never been studied. Deciphering the molecular machinery of isoform 2 internalisation should contribute to a better understanding of its pathophysiological role. First, we demonstrated in our cellular context that both isoforms of L1CAM are mainly a clathrin-independent cargo, which was not expected for isoform 1. Second, the mechanism of L1CAM endocytosis is specifically mediated by the N-BAR domain protein endophilin-A3. Third, we discovered PSTPIP1, an F-BAR domain protein, as a novel actor in this endocytic process. Finally, we identified galectins as endocytic partners and negative regulators of L1CAM endocytosis. In summary, the interplay of the BAR proteins endophilin-A3 and PSTPIP1, and galectins fine tune the clathrin-independent endocytosis of L1CAM.

The role of miRNA in prostate cancer diagnosis, prognosis and treatment response: a narrative review.

To date, prostate cancer remains the most common tumor diagnosed in males and the second most common cause of cancer-related mortality. While current screening protocols can detect early disease, they lack enough sensitivity and specificity, leading to unnecessary biopsies and overtreatment. Furthermore, disease monitoring remains challenging, as current prognostic strategies rely on data obtained by invasive means such as biopsy, surgery and digital rectal examination. Additionally, there are no tools to predict tumor progression, risk reclassification and treatment response. As the need for accurate biomarkers continues, miRNAs are promising biomarkers for screening, surveillance, prognosis and treatment response in prostate cancer. In this review, the authors describe the current evidence regarding the accuracy and efficacy of these biomarkers for prostate cancer.

SPITFIR(e): a supermaneuverable algorithm for fast denoising and deconvolution of 3D fluorescence microscopy images and videos.

Modern fluorescent microscopy imaging is still limited by the optical aberrations and the photon budget available in the specimen. A direct consequence is the necessity to develop flexible and "off-road" algorithms in order to recover structural details and improve spatial resolution, which is critical when restraining the illumination to low levels in order to limit photo-damages. Here, we report SPITFIR(e) a flexible method designed to accurately and quickly restore 2D-3D fluorescence microscopy images and videos (4D images). We designed a generic sparse-promoting regularizer to subtract undesirable out-of-focus background and we developed a primal-dual algorithm for fast optimization. SPITFIR(e) is a "swiss-knife" method for practitioners as it adapts to any microscopy techniques, to various sources of signal degradation (noise, blur), to variable image contents, as well as to low signal-to-noise ratios. Our method outperforms existing state-of-the-art algorithms, and is more flexible than supervised deep-learning methods requiring ground truth datasets. The performance, the flexibility, and the ability to push the spatiotemporal resolution limit of sub-diffracted fluorescence microscopy techniques are demonstrated on experimental datasets acquired with various microscopy techniques from 3D spinning-disk confocal up to lattice light sheet microscopy.

Stale bread waste recycling as ingredient for fresh oven-baked white bread: effects on dough viscoelasticity, bread molecular organization, texture, and starch digestibility.

BACKGROUND: Wasted food produced for human consumption is estimated at 33% globally, and bread is the food product with the highest percentage. There is an ongoing drive to reincorporate food waste still useful and safe into the production chain of food for human consumption. This work aims to contribute to the study of the feasibility of recycling stale bread waste flour (BWF) into fresh oven-baked white bread, by replacing 0, 20, 40, 60, 80, and 100 g/100 g of the wheat flour with BWF. RESULTS: Storage and loss moduli increased as the BWF content increased. The baked loaf exhibited decreased lightness and yellowness but increased redness. Increasing BWF contents produced decreased loaf volume and hardness but increased moisture content. Fourier-transform infrared analysis showed that the BWF addition induced important changes in the water, protein, and starch molecular organization. Therefore, starch digestibility showed reductions in both rapidly and slowly digestible starch fractions. Principal component analysis revealed that replacements of up 20 g/100 g can produce white bread with textural, colour, and starch digestibility characteristics like that of the control bread. CONCLUSION: The fresh oven-baked white bread variation produced by replacing 20 g/100 g of the wheat flour with BWF exhibited comparable colour, volume, texture, and starch digestibility features as a control bread did made with 0 g/100 BWF. Higher replacement percentages of wheat flour by stale BWF produced unsuitable drawbacks in the white bread characteristics, but those might be deemed as convenient in other types of bakery products. © 2023 Society of Chemical Industry.

Tissue- and cell-specific whole-transcriptome meta-analysis from brain and retina reveals differential expression of dystrophin complexes and new dystrophin spliced isoforms.

The large DMD gene encodes a group of dystrophin proteins in brain and retina, produced from multiple promoters and alternative splicing events. Dystrophins are core components of different scaffolding complexes in distinct cell types. Their absence may thus alter several cellular pathways, which might explain the heterogeneous genotype-phenotype relationships underlying central comorbidities in Duchenne muscular dystrophy (DMD). However, the cell-specific expression of dystrophins and associated proteins (DAPs) is still largely unknown. The present study provides a first RNA-Seq-based reference showing tissue- and cell-specific differential expression of dystrophins, splice variants and DAPs in mouse brain and retina. We report that a cell type may express several dystrophin complexes, perhaps due to expression in separate cell subdomains and/or subpopulations, some of which with differential expression at different maturation stages. We also identified new splicing events in addition to the common exon-skipping events. These include a new exon within intron 51 (E51b) in frame with the flanking exons in retina, as well as inclusions of intronic sequences with stop codons leading to the presence of transcripts with elongated exons 40 and/or 41 (E40e, E41e) in both retina and brain. PCR validations revealed that the new exons may affect several dystrophins. Moreover, immunoblot experiments using a combination of specific antibodies and dystrophin-deficient mice unveiled that the transcripts with stop codons are translated into truncated proteins lacking their C-terminus, which we called N-Dp427 and N-Dp260. This study thus uncovers a range of new findings underlying the complex neurobiology of DMD.

Challenges of intracellular visualization using virtual and augmented reality.

Microscopy image observation is commonly performed on 2D screens, which limits human capacities to grasp volumetric, complex, and discrete biological dynamics. With the massive production of multidimensional images (3D + time, multi-channels) and derived images (e.g., restored images, segmentation maps, and object tracks), scientists need appropriate visualization and navigation methods to better apprehend the amount of information in their content. New modes of visualization have emerged, including virtual reality (VR)/augmented reality (AR) approaches which should allow more accurate analysis and exploration of large time series of volumetric images, such as those produced by the latest 3D + time fluorescence microscopy. They include integrated algorithms that allow researchers to interactively explore complex spatiotemporal objects at the scale of single cells or multicellular systems, almost in a real time manner. In practice, however, immersion of the user within 3D + time microscopy data represents both a paradigm shift in human-image interaction and an acculturation challenge, for the concerned community. To promote a broader adoption of these approaches by biologists, further dialogue is needed between the bioimaging community and the VR&AR developers.

Telemedicine for medical abortion service provision in Mexico: A safety, feasibility, and acceptability study.

OBJECTIVE: We aimed to obtain evidence about the safety, acceptability, and feasibility of a direct-to-patient telemedicine medical abortion service in Mexico's private health sector. STUDY DESIGN: A prospective observational one-group study to evaluate a telemedicine abortion service, referred to as TeleAborto, was conducted at three private clinics and one nonclinician community-based provider. Information about the study was provided by phone, websites, and social media. Abortion seekers were screened for eligibility and underwent any pre-abortion tests requested by the study site at services close to home. Eligible participants received packages with abortion medication, analgesics, and instructions and a remote follow-up contact was scheduled for 7 to 14 days later. Primary outcomes include abortion outcome, management of adverse events, acceptability, and feasibility measures such as package reception and follow-up contact, and challenges to get pre- and post-abortion tests. RESULTS: We conducted 581 screenings and sent 378 study packages, all successfully received, reaching abortion seekers in all 32 states. All participants took medications before 70 days gestational age as per study protocol. Abortion outcome was determined for 87% of participants (330/378); 93% (306/330) had a successful abortion without intervention and 18 with intervention; 6 individuals decided to continue the pregnancy. Participants reported high satisfaction with TeleAborto, citing convenience as their most valued aspect (85%; 264/311). CONCLUSIONS: This study showed that guided self-managed telemedicine abortion is safe, acceptable, and feasible in Mexico. The model has the potential to close the access gap for indigenous and rural populations, and those that rely on public sector services. IMPLICATIONS: The findings contribute evidence in support of telemedicine models for early medical abortion, demonstrating the feasibility of a self-management protocol implemented with supportive health care providers and the potential for a broad geographical reach in Mexico.