Photobiomodulation efficacy in age-related macular degeneration: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of vision loss. Photobiomodulation (PBM) offers a controversial approach for managing dry AMD, aiming to halt or reverse progression through mitochondrial activity modulation. However, the efficacy and clinical relevance of PBM as a potential approach for managing dry AMD remain debated. METHODS: We systematically searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) comparing PBM versus a sham in patients with dry AMD. We performed trial sequential analysis (TSA) and minimal clinically important difference (MCID) calculations to assess statistical and clinical significance applying a random-effects model with 95% confidence intervals (CI). RESULTS: We included three RCTs comprising 247 eyes. The pooled analysis showed that PBM significant improved BCVA (MD 1.76 letters; 95% CI: 0.04 to 3.48) and drusen volume (MD -0.12 mm³; 95% CI: -0.22 to -0.02) as compared with a sham control. However, the TSA indicated that the current sample sizes were insufficient for reliable conclusions. No significant differences were observed in GA area. The MCID analysis suggested that the statistically significant results did not translate into clinically significant benefits. In the quality assessment, all studies were deemed to have a high risk of bias. CONCLUSION: This meta-analysis points limitations in the current evidence base for PBM in dry AMD treatment, with issues around small sample sizes. Statistically significant improvements do not translate into clinical benefits. The research underscores need for larger RCTs to validate PBM's therapeutic potential for dry AMD.

Exosomas como tratamiento alternativo del síndrome genitourinario de la menopausia / Exosomes as an alternative treatment for genitourinary syndrome of menopause

Objetivo: Evaluar el efecto de los exosomas como tratamiento alternativo en la restauración del síndrome genitourinario de la menopausia en pacientes que acuden a una consulta ginecológica, en Valencia, Estado Carabobo, en el período junio - agosto de 2023. Métodos: Estudio prospectivo, descriptivo, exploratorio, incluyó tres casos de mujeres con diagnóstico de síndrome genitourinario de la menopausia. Se evaluó la respuesta en cuanto a los síntomas, examen clínico según el índice de salud vaginal, la satisfacción con el tratamiento y la tolerabilidad. Se aplicó el tratamiento con exosomas: 2 cc con técnica de punto a punto en todas las paredes vaginales y 1 cc en el vestíbulo, en 3 sesiones, con intervalo de 15 días. Resultados: La edad de las pacientes estuvo entre 53 y 56 años, con un promedio de tiempo de menopausia de 6,6 años. Previo al tratamiento, había un nivel alto de irritación vaginal (100 %), dolor en el introito (100 %), sequedad vaginal, dispareunia, hipersensibilidad y las no relaciones sexuales (66,67 %). Postratamiento predominó la ausencia de los síntomas: sequedad vaginal, dispareunia, hipersensibilidad y dolor en introito (100 %); irritación vaginal y no relaciones sexuales (66,67 %) (p = 0,0001). La mediana del índice de salud vaginal previa fue 13 (10 ­ 13) y posterior fue 18 (17 ­ 20) (p = 0,0476). La satisfacción y tolerabilidad fue de 66,67 %. Una paciente refirió dolor leve. Conclusión: La terapia con exosomas es eficaz para reducir los síntomas y signos del síndrome genitourinario de la menopausia, y bien tolerado(AU)

Objective: To evaluate the effect of exosomes as an alternative treatment in the restoration of genitourinary syndrome of menopause in patients attending a gynecological consultation in Valencia, Carabobo State, in the period June - August 2023. Methods: A prospective, descriptive, exploratory study included three cases of women diagnosed with genitourinary syndrome of menopause. Response was assessed in terms of symptoms, clinical examination according to vaginal health index, satisfaction with treatment and tolerability. Treatment with exosomes was applied: 2 cc with point-to-point technique on all vaginal walls and 1 cc in the vestibule, in 3 sessions, with an interval of 15 days. Results: The age of the patients was between 53 and 56 years, with a mean menopause time of 6.6 years. Prior to treatment, there was a high level of vaginal irritation (100%), pain in the introitus (100%), vaginal dryness, dyspareunia, hypersensitivity and non-sexual intercourse (66.67%). Post-treatment, the absence of symptoms predominated: vaginal dryness, dyspareunia, hypersensitivity and pain in the introitus (100%); vaginal irritation and no sexual intercourse (66.67%) (p = 0.0001). The median index of previous vaginal health was 13 (10 ­ 13) and subsequent was 18 (17 ­ 20) (p = 0.0476). Satisfaction and tolerability was 66.67%. One patient reported mild pain. Conclusion: Exosome therapy is effective in reducing the symptoms and signs of genitourinary syndrome of menopause, and well tolerated(AU)

Communicating the diagnosis of spinal muscular atrophy in endogamous vs. non-endogamous regions.

INTRODUCTION: The high prevalence of endogamy, or inbreeding, in northeastern Brazil, is due to historical and cultural factors, with large families living in cities far from the coast and subject to low socioeconomic and infrastructure levels. This breeding practice results in low genetic variability with an increased prevalence of rare autosomal recessive and neurodegenerative diseases, such as spinal muscular atrophy (SMA). OBJECTIVE: Understanding the impact of communicating the diagnosis of SMA on the mental health of patients and their families and the differences between the Northeast (endogamous region) and the other regions of Brazil (non-endogamous ones). METHODS: Cross-sectional study obtained through a structured questionnaire about the moment of receiving the SMA diagnosis, containing the Impact of Event Scale-Revised. RESULTS AND DISCUSSION: The sample consisted of 100 volunteers from all regions of Brazil, 47 patients diagnosed with SMA and 53 family members present at the time of the diagnosis. There was a predominance of females (83%) and homogeneity between the groups for the variables gender, age, color, education, religion, and SMA subtype (1, 2, 3, and 4). The Northeast region, representing 43% of the sample, despite being less economically favored, showed greater satisfaction with medical care and inclusion in health services, with less self-reported psychological trauma and fewer signs of post-traumatic stress disorder (PTSD) related to the moment of receiving the diagnosis. The non-endogamous regions, in turn, reported the presence of strong waves of emotion, sleep problems, feelings of irritability, anger, and the presence of bad thoughts related to this situation. CONCLUSION: The feeling of inclusion in health services and satisfaction with medical care in the endogamous region had a positive impact on the mental health of those involved, reducing psychological trauma and signs of PTSD arising from the communication of the SMA diagnosis.

Integrated Approaches and Practical Recommendations in Patient Care Identified with 5q Spinal Muscular Atrophy through Newborn Screening.

In recent years, significant progress has been made in 5q Spinal Muscular Atrophy therapeutics, emphasizing the importance of early diagnosis and intervention for better clinical outcomes. Characterized by spinal cord motor neuron degeneration, 5q-SMA leads to muscle weakness, swallowing difficulties, respiratory insufficiency, and skeletal deformities. Recognizing the pre-symptomatic phases supported by screening and confirmatory genetic tests is crucial for early diagnosis. This work addresses key considerations in implementing 5q-SMA screening within the Brazilian National Newborn Screening Program and explores Brazil's unique challenges and opportunities, including genetic tests, time-to-patient referral to specialized centers, program follow-up, and treatment algorithms. We aim to guide healthcare professionals and policymakers, facilitating global discussions, including Latin American countries, and knowledge-sharing on this critical subject to improve the care for newborns identified with 5q SMA.

Remobilization with whole-body vibration improves functionality, histomorphometric parameters, and AQP1 expression in the soleus muscle of Wistar rats.

Background: Whole-body vibration (WBV) is used to enhance physical performance in sports and rehabilitation. The present study analyzed the effects of remobilization with WBV on the soleus muscle of Wistar rats. Methods: Twenty-eight animals were separated into four experimental groups (n = 7): CON (control); IM (immobilized); FR (immobilization and free remobilization); and WBV (immobilization and remobilization with WBV). The immobilization of the pelvic limb was carried out according to the standard protocol using a plaster cast for 15 days. For remobilization with WBV, a Frequency of 60 Hz was applied for 10 min, five days a week, for two weeks. After the remobilization period, the animals were euthanized, and the right soleus muscle was dissected followed by processing for histomorphometric analysis and immunolocalization of Aquaporin 1 (AQP1). Results: We observed a reduced larger diameter in IM compared to CON, with restored values in WBV. For the estimation of connective tissue, a significant increase was observed in the immobilized groups, while a reduction was noted in the remobilized groups. AQP1 expression decreased significantly in IM and increased in WBV. Conclusion: Immobilization caused morphofunctional damage to the soleus muscle, and remobilization with WBV is efficient and offers advantages over free remobilization.

The effects of various therapies on vulvovaginal atrophy and quality of life in gynecological cancer patients: a systematic review.

PURPOSE: Tumors affecting the female genital tract and their treatments have the potential to induce adverse modifications in vaginal health and impact personal aspects of patient's lives. Vulvovaginal atrophy is one of the morphological changes observed in individuals with a history of gynecological cancer, influenced both by the biological environment of tumors and the main therapeutic modalities employed. Therefore, the purpose of this study was to identify approaches to treat vulvovaginal atrophy while assessing the impact on the emotional and sexual health of women diagnosed with gynecological cancers. METHODS: To achieve this goal, a systematic review was conducted following the methodological guidelines outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The databases used for literature research were PubMed and Web of Science. RESULTS: Initially, 886 articles were obtained. After eliminating duplicates and applying inclusion/exclusion criteria, seven articles were selected for analysis. The period of highest publication activity spanned from 2017 to 2020, with the majority conducted in Italy. Five treatment modalities were identified and categorized as vaginal suppository, oral medication, surgical procedure, CO2 laser therapy, and vaginal dilator. Twenty-four outcomes related to vaginal health and 30 outcomes related to overall, sexual, and emotional quality of life were analyzed. CONCLUSION: In general, all interventions demonstrated the ability to improve vaginal health or, at the very least, the sexual health of patients. Thus, despite limitations, all treatments have the potential to address vulvovaginal atrophy in patients with a history of gynecological cancer.

Myogenic microRNAs as Therapeutic Targets for Skeletal Muscle Mass Wasting in Breast Cancer Models.

Breast cancer is the type of cancer with the highest prevalence in women worldwide. Skeletal muscle atrophy is an important prognostic factor in women diagnosed with breast cancer. This atrophy stems from disrupted skeletal muscle homeostasis, triggered by diminished anabolic signalling and heightened inflammatory conditions, culminating in an upregulation of skeletal muscle proteolysis gene expression. The importance of delving into research on modulators of skeletal muscle atrophy, such as microRNAs (miRNAs), which play a crucial role in regulating cellular signalling pathways involved in skeletal muscle protein synthesis and degradation, has been recognised. This holds true for conditions of homeostasis as well as pathologies like cancer. However, the determination of specific miRNAs that modulate skeletal muscle atrophy in breast cancer conditions has not yet been explored. In this narrative review, we aim to identify miRNAs that could directly or indirectly influence skeletal muscle atrophy in breast cancer models to gain an updated perspective on potential therapeutic targets that could be modulated through resistance exercise training, aiming to mitigate the loss of skeletal muscle mass in breast cancer patients.

Ospemifene for Genitourinary Syndrome of Menopause: Patient Selection.

Vulvar vaginal atrophy is a common condition affecting postmenopausal women, significantly impacting their quality of life. Fortunately, various treatment options are available, ranging from hormonal to non-hormonal therapies. Ospemifene has emerged as a promising non-hormonal alternative for managing vulvar vaginal atrophy. Its targeted approach, unique mechanism of action, favorable safety profile particularly for breast tissue, and efficacy make it a valuable option for women seeking relief from symptoms such as vaginal pain, dryness and dyspareunia and cannot receive estrogen supplementations. This is particularly the case for breast cancer survivors or women with a significant family history of estrogen-dependent cancers. Hence, tailored treatment plans, considering individual preferences and health circumstances, are essential in optimizing outcomes and improving the overall well-being of affected individuals.

Cuidados respiratorios en pacientes con atrofia muscular espinal para evitar el fallo ventilatorio agudo y la traqueostomía: revisión literaria y recomendaciones consensuadas / Respiratory care in patients with spinal muscular atrophy to avoid acute ventilatory failure and tracheostomy: literature review and consensus recommendations

La atrofia muscular espinal (AME) 5q es una de las enfermedades neuromusculares de mayor incidencia en la infancia. Sin embargo, la prevalencia de AME tipo 1, su forma más severa de presentación, es menor debido a muertes prematuras evitables antes de los dos años por insuficiencia ventilatoria subtratada. La irrupción de nuevos tratamientos modificadores de la enfermedad pueden cambiar dramáticamente este pronóstico y es una oportunidad para actualizar el manejo respiratorio, a través de cuidados estandarizados básicos, preferentemente no invasivos, abordando la debilidad de los músculos respiratorios, la insuficiencia tusígena y ventilatoria, con un enfoque preventivo. La siguiente revisión literaria entrega estrategias para evitar la intubación y la traqueostomía usando soporte ventilatorio no invasivo (SVN), reclutamiento de volumen pulmonar (RVP) y facilitación de la tos. Se analizan en detalle los protocolos de extubación en niños con AME tipo 1.

Spinal muscular atrophy (SMA) 5q is one of the neuromuscular diseases with the highest incidence in childhood. Nevertheless, the prevalence of its most severe form SMA1 is lower due to premature preventable deaths before two years of age related to ventilatory insufficiency undertreated. The emergence of new disease-modifying treatments can dramatically change this prognosis and is an opportunity to update respiratory management, through basic standardized care, mostly non-invasive, addressing respiratory muscles pump weakness, cough and ventilatory insufficiency with a preventive approach. This literature review provides consensus recommendations for strategies to avoid intubation and tracheostomy using noninvasive ventilatory support (NVS), lung volume recruitment (LVR), and cough facilitation. Extubation protocols in children with SMA type 1 are analyzed in detail.

Leptin receptor reactivation restores brain function in early-life Lepr-deficient mice.

Obesity is a chronic disease caused by excessive fat accumulation that impacts the body and brain health. Insufficient leptin or leptin receptor (LepR) is involved in the disease pathogenesis. Leptin is involved with several neurological processes, and it has crucial developmental roles. We have previously demonstrated that leptin deficiency in early life leads to permanent developmental problems in young adult mice, including an imbalance in energy homeostasis, alterations in melanocortin and the reproductive system and a reduction in brain mass. Given that in humans, obesity has been associated with brain atrophy and cognitive impairment, it is important to determine the long-term consequences of early-life leptin deficiency on brain structure and memory function. Here, we demonstrate that leptin-deficient (LepOb) mice exhibit altered brain volume, decreased neurogenesis and memory impairment. Similar effects were observed in animals that do not express the LepR (LepRNull). Interestingly, restoring the expression of LepR in 10-week-old mice reverses brain atrophy, in addition to neurogenesis and memory impairments in older animals. Our findings indicate that leptin deficiency impairs brain development and memory, which are reversible by restoring leptin signalling in adulthood.

Predicting outcomes after kidney transplantation: Can Pareto's rules help us to do so?

Kidney transplantation is the best option for kidney replacement therapy, even considering that most of the times the grafts do not survive as long as their recipients. In the Khalil et al's experience, published in this issue of the Journal, they analyze their second kidney graft survival and describe those significant predictors of early loss. This editorial comments on the results and put in perspec tive that most of the times, long-term graft survival could be inadvertently jeopardized if the immunosuppressive therapy is reduced or withdrawn for any reason, and that it could happen frequently if the transplant physician intends to innovate with the clinical care without proper evidence-based data.

Macular atrophy and focal choroidal excavation in a patient with JAG1- related alagille syndrome.

INTRODUCTION: Alagille syndrome (AGS) is a genetic disease with multisystemic affection, including ocular manifestations. Recently, a high frequency of posterior segment findings, including macular changes, has been reported. This publication aims to report an unusual finding of macular atrophy and a focal choroidal excavation in a patient with JAG1 related AGS. METHODS: Case report. RESULTS: This publication describes an atypical presentation of focal choroidal excavation (FCE) and unilateral macular atrophy in a 7-year-old male with Alagille syndrome (AGS). Genetic analysis revealed a pathogenic variant in the JAG1 gene. Ophthalmological examination and imaging findings demonstrated characteristic ocular manifestations of AGS, including posterior embryotoxon, chorioretinal atrophy, and thinning of the choroid. CONCLUSION: The presence of FCE in AGS is uncommon, and the underlying mechanisms remain unclear. Further exploration of similar cases is necessary to better understand the evolution and visual prognosis in patients with AGS and FCE.

This case report highlights the presence of focal choroidal excavation and unilateral macular atrophy in a patient with Alagille syndrome. The genetic analysis identified a pathogenic variant in the JAG1 gene.

Serum myostatin as a candidate disease severity and progression biomarker of spinal muscular atrophy.

The identification of biomarkers for spinal muscular atrophy is crucial for predicting disease progression, severity, and response to new disease-modifying therapies. This study aimed to investigate the role of serum levels of myostatin and follistatin as biomarkers for spinal muscular atrophy, considering muscle atrophy secondary to denervation as the main clinical manifestation of the disease. The study evaluated the differential gene expression of myostatin and follistatin in a lesional model of gastrocnemius denervation in mice, as well as in a meta-analysis of three datasets in transgenic mice models of spinal muscular atrophy, and in two studies involving humans with spinal muscular atrophy. Subsequently, a case-control study involving 27 spinal muscular atrophy patients and 27 controls was conducted, followed by a 12-month cohort study with 25 spinal muscular atrophy cases. Serum levels of myostatin and follistatin were analysed using enzyme-linked immunosorbent assay at a single centre in southern Brazil. Skeletal muscle gene expression of myostatin decreased and of follistatin increased following lesional muscle denervation in mice, consistent with findings in the spinal muscular atrophy transgenic mice meta-analysis and in the iliopsoas muscle of five patients with spinal muscular atrophy type 1. Median serum myostatin levels were significantly lower in spinal muscular atrophy patients (98 pg/mL; 5-157) compared to controls (412 pg/mL; 299-730) (P < 0.001). Lower myostatin levels were associated with greater disease severity based on clinician-rated outcomes (Rho = 0.493-0.812; P < 0.05). After 12 months, there was a further reduction in myostatin levels among spinal muscular atrophy cases (P = 0.021). Follistatin levels did not differ between cases and controls, and no significant changes were observed over time. The follistatin:myostatin ratio was significantly increased in spinal muscular atrophy subjects and inversely correlated with motor severity. Serum myostatin levels show promise as a novel biomarker for evaluating the severity and progression of spinal muscular atrophy. The decrease in myostatin levels and the subsequent favourable environment for muscle growth may be attributed to denervation caused by motor neuron dysfunction.

Stroke related sarcopenia in individuals with different physical activity levels: A cross-sectional study.

BACKGROUND AND OBJECTIVE: Individuals after stroke are likely to deal with the possible development of sarcopenia and reduced physical activity levels. The purpose of this study was to compare sarcopenia of individuals with chronic stroke who were stratified according to their physical activity levels, and to evaluate the relationship between sarcopenia and physical activity levels. MATERIALS AND METHODS: This cross-sectional study was conducted with individuals after chronic stroke recruited from the general community. Individuals were submitted to sarcopenia screening (SARC-F questionnaire) and assessment of physical activity levels (Human Activity Profile questionnaire) to classify the individuals as impaired, moderately active, and active according to their Adjusted Activity Status (AAS). ANOVA was used to investigate the sarcopenia between groups and Pearson's coefficient to investigate the association among variables. RESULTS: Fifty-four individuals with a mean age of 56 ± 17.4 years were included. Twenty-one percent of the individuals were screened for sarcopenia. Inactive individuals had higher mean scores in the SARC-F (3.6 ± 2.1 points), whereas moderately active and active individuals presented lower mean scores in the same questionnaire, being 1.2 ± 1.1 points and 0.5 ± 0.7 points, respectively. A statistically significant inverse and high association was found between sarcopenia and physical activity levels (r = -0.716; p < 0.01). CONCLUSION: Sarcopenia was found to be higher in individuals after chronic stroke with lower physical activity levels considered inactive when compared to individuals with higher physical activity levels. Furthermore, there was an inverse relationship between sarcopenia and physical activity level in stroke survivors.

eTEP Rives-Stoppa impact on abdominal contour: a retrospective observational and clinical quality improvement study using Ellipse 9 tool.

BACKGROUND: The eTEP Rives-Stoppa (RS) procedure, increasingly used for ventral hernia repair, has raised concerns about postoperative upper abdominal bulging. This study aims to objectively evaluate changes in the abdominal contour after eTEP RS and explore potential causes using a novel analytical tool, the Ellipse 9. METHODS: Thirty patients undergoing eTEP RS without posterior rectus sheath closure were assessed before and 3 months after surgery using CT scan images. Key measurements analyzed included the distance between linea semilunaris (X2), eccentricity over the Cord (c/a Cord), superior eccentricity (c/a Sup), Y2, and the superior perimeter of the abdomen. The Ellipse 9 tool, which provides graphical images and numerical representations, was utilized alongside patient-reported outcomes to assess perceived abdominal changes. RESULTS: The study group exhibited a trend toward a flatter abdomen with reduced distance between linea semilunaris(X2). However, 17% of patients developed upper abdominal bulging (5). Significant differences in c/a Cord, c/a Sup, Y2, and the superior perimeter of the abdomen, confirmed with Bonferroni corrections, were noted between bulging (5 patients) and non-bulging groups (25 patients). There was a notable disparity between patient perceptions and objective outcomes. CONCLUSION: The eTEP RS procedure improved abdominal contour in most patients from a selected cohort. The Ellipse 9 tool was valuable for the objective analysis of these changes. The cause of bulging post-eTEP RS is probably multifactorial. Notably, there was often a discrepancy between patient perceptions of bulging and objective clinical findings.

Nuevos paradigmas en atrofia muscular espinal de presentación temprana: siempre es bueno recordar / New paradigms in early-onset spinal muscular atrophy: a reminder is always beneficial

La atrofia muscular espinal (AME) de presentación temprana representa la variante más severa, con una expectativa de vida generalmente no mayor a dos años sin soporte ventilatorio, debido a la insuficiencia respiratoria y la dificultad para toser. Tradicionalmente, el manejo respiratorio en muchos países ha incluido la traqueostomía para proporcionar asistencia ventilatoria invasiva de manera continua. No obstante, la introducción de medicamentos de precisión ha modificado la progresión natural de la enfermedad, evidenciando mejoras significativas en los hitos motores y beneficiando también la función respiratoria. A pesar de estas mejoras, en muchos casos sigue siendo necesaria la ventilación intermitente y/o continua, además de la facilitación de la tos. Estas necesidades pueden abordarse de forma no invasiva mediante el soporte ventilatorio no invasivo (SVN), la in-exsuflación mecánica (IEM) y el reclutamiento de volumen pulmonar (RVP), que son considerados pilares del tratamiento respiratorio en enfermedades neuromusculares. Estas estrategias promueven el desarrollo y mantenimiento de la función respiratoria, reduciendo el riesgo de exacerbaciones respiratorias que podrían llevar a intubaciones evitables. Comúnmente, los pacientes con AME experimentan intentos fallidos de extubación siguiendo protocolos tradicionales, siendo catalogados como no extubables y potenciales candidatos a traqueostomía. No obstante, existen protocolos de extubación específicos para AME que emplean SVN e IEM con un alto porcentaje de éxito, evitando traqueostomías innecesarias que pueden complicar la progresión de la enfermedad y afectar la calidad de vida. El enfoque respiratorio no invasivo es una opción de manejo segura tanto en el hospital como en el hogar, ofreciendo una mejor calidad de vida para los pacientes y sus familias.

Early-onset spinal muscular atrophy (SMA) is the most severe variant, with a life expectancy generally not exceeding two years without ventilatory support due to respiratory insufficiency and difficulty in coughing. Traditionally, respiratory management in many countries has included tracheostomy to provide continuous invasive ventilatory support. However, the introduction of precision medicine has altered the natural progression of the disease, showing significant improvements in motor milestones and also benefiting respiratory function. Despite these improvements, many cases still require intermittent and/or continuous ventilation, as well as cough facilitation. These needs can be addressed non-invasively through non-invasive ventilatory support (NIV), mechanical insufflation-exsufflation (MIE), and lung volume recruitment (LVR), which are considered the pillars of respiratory treatment in neuromuscular diseases. These strategies promote the development and maintenance of respiratory function, reducing the risk of respiratory exacerbations that could lead to avoidable intubations. Commonly, SMA patients experience failed extubation attempts following traditional protocols, being labeled as non-extubatable and potential candidates for tracheostomy. Nevertheless, there are specific extubation protocols for SMA that employ NIV and MIE with a high success rate, avoiding unnecessary tracheostomies that can complicate disease progression and impact quality of life. The non-invasive respiratory approach is a safe management option both in the hospital and at home, offering a better quality of life for patients and their families.

Visual Agnosia Mimicking Memory Impairment: A Case Report of Posterior Cortical Atrophy.

Vision specialists will benefit from increased awareness of posterior cortical atrophy (PCA) syndrome. Failure to adequately identify the chief complaint as a visual symptom may lead to incorrect diagnosis or diagnostic delay. A previously healthy, 59-year-old woman presented with a 5-year history of 'losing her stuff'. Upon psychiatric and neuro-ophthalmological evaluation, this symptom was better recognised as a feature of visual agnosia and simultanagnosia. She also presented with multiple previously unrecognised symptoms indicative of higher visual processing dysfunction, such as alexia without agraphia, ocular motor apraxia, optic ataxia, prosopagnosia, akinetopsia and topographagnosia, so further assessment to investigate for PCA was carried out. After a work-up including cognitive assessment, brain structural/functional imaging, and laboratory tests she was diagnosed with visual-variant Alzheimer's disease. Patients with PCA merit a detailed review of their symptoms, as well as the use of office tests such as cognitive evaluation tools, different types of perimetry, colour vision tests, and non-delayed psychiatric consultation for correct management and assessment. This report will emphasise five key aspects to be considered when evaluating patients with PCA.

Modeling Spinal Muscular Atrophy in Zebrafish: Current Advances and Future Perspectives.

Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease characterized by degeneration of lower motor neurons (LMNs), causing muscle weakness, atrophy, and paralysis. SMA is caused by mutations in the Survival Motor Neuron 1 (SMN1) gene and can be classified into four subgroups, depending on its severity. Even though the genetic component of SMA is well known, the precise mechanisms underlying its pathophysiology remain elusive. Thus far, there are three FDA-approved drugs for treating SMA. While these treatments have shown promising results, their costs are extremely high and unaffordable for most patients. Thus, more efforts are needed in order to identify novel therapeutic targets. In this context, zebrafish (Danio rerio) stands out as an ideal animal model for investigating neurodegenerative diseases like SMA. Its well-defined motor neuron circuits and straightforward neuromuscular structure offer distinct advantages. The zebrafish's suitability arises from its low-cost genetic manipulation and optical transparency exhibited during larval stages, which facilitates in vivo microscopy. This review explores advancements in SMA research over the past two decades, beginning with the creation of the first zebrafish model. Our review focuses on the findings using different SMA zebrafish models generated to date, including potential therapeutic targets such as U snRNPs, Etv5b, PLS3, CORO1C, Pgrn, Cpg15, Uba1, Necdin, and Pgk1, among others. Lastly, we conclude our review by emphasizing the future perspectives in the field, namely exploiting zebrafish capacity for high-throughput screening. Zebrafish, with its unique attributes, proves to be an ideal model for studying motor neuron diseases and unraveling the complexity of neuromuscular defects.

Development of a low-cost and accurate carrier screening method for spinal muscular atrophy in developing countries.

Heterozygous carriers of the survival of motor neuron 1 (SMN1) gene deletion in parents account for approximately 95% of neonatal spinal muscular atrophy cases. Given the severity of the disease, professional organizations have recommended periconceptional spinal muscular atrophy carrier screening to all couples, regardless of race or ethnicity. However, the prevalence of screening activities in mainland China remains suboptimal, mainly attributed to the limitations of the existing carrier screening methods. Herein, we aimed to develop a low-cost, accessible, and accurate carrier screening method based on duplex droplet digital PCR (ddPCR), to cover a wider population in developing countries, including China. The receiver operating characteristic curve was used to determine the cut-off value of SMN1 copy numbers. Performance validation was conducted for linearity, precision, and accuracy. In total, 482 cases were considered to validate the concordance between the developed ddPCR assay and multiplex ligation-dependent probe amplification. Linear correlations were excellent between the expected concentration of the reference gene and the observed values (R2 > 0.99). Both the intra- and inter-assay precision of our ddPCR assays were less than 6.0%. The multiplex ligation-dependent probe amplification and ddPCR results were consistent in 480 of the 482 cases (99.6%). Two cases with multiplex ligation-dependent probe amplification, suggestive of two copies of SMN1 exon 7, were classified into three copies by ddPCR analysis. The overall correct classification of the samples included in our ddPCR assay was 100%. This study demonstrates that an appropriate cut-off value is an important prerequisite for establishing a semi-quantitative method to determine the SMN1 copy numbers. Compared to conventional methods, our ddPCR assay is low-cost, highly accurate, and has full potential for application in population spinal muscular atrophy carriers screening.

Identification of metabolic pathways and key genes associated with atypical parkinsonism using a systems biology approach.

Atypical parkinsonism (AP) is a group of complex neurodegenerative disorders with marked clinical and pathophysiological heterogeneity. The use of systems biology tools may contribute to the characterization of hub-bottleneck genes, and the identification of its biological pathways to broaden the understanding of the bases of these disorders. A systematic search was performed on the DisGeNET database, which integrates data from expert curated repositories, GWAS catalogues, animal models and the scientific literature. The tools STRING 11.0 and Cytoscape 3.8.2 were used for analysis of protein-protein interaction (PPI) network. The PPI network topography analyses were performed using the CytoHubba 0.1 plugin for Cytoscape. The hub and bottleneck genes were inserted into 4 different sets on the InteractiveVenn. Additional functional enrichment analyses were performed to identify Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology for a described set of genes. The systematic search in the DisGeNET database identified 485 genes involved with Atypical Parkinsonism. Superimposing these genes, we detected a total of 31 hub-bottleneck genes. Moreover, our functional enrichment analyses demonstrated the involvement of these hub-bottleneck genes in 3 major KEGG pathways. We identified 31 highly interconnected hub-bottleneck genes through a systems biology approach, which may play a key role in the pathogenesis of atypical parkinsonism. The functional enrichment analyses showed that these genes are involved in several biological processes and pathways, such as the glial cell development, glial cell activation and cognition, pathways were related to Alzheimer disease and Parkinson disease. As a hypothesis, we highlight as possible key genes for AP the MAPT (microtubule associated protein tau), APOE (apolipoprotein E), SNCA (synuclein alpha) and APP (amyloid beta precursor protein) genes.