Specific Treatment Research Articles

Physical activity for muscle rehabilitation in sarcopenia

Background: sarcopenia is a progressive and generalized clinical condition associated with loss of mass, strength, and/or muscle function, impairing physical performance. The definition of sarco-penia is a dilemma, as several studies have been published in the last ten years by different socie-ties. One of the most used definitions is the Guideline created by the European Working Group on Sarcopenia in Older People (EWGSOP) and updated in 2019 (EWGSOP2) to facilitate the under-standing of sarcopenia and improve treatment proposals. This is the only definition supported by several international scientific societies for clinical practice and research in patients with sarcope-nia. Treatment can be divided into non-pharmacological and pharmacological. There are no spe-cific drugs approved for the treatment of sarcopenia. As for non-pharmacological interventions, physical exercise is the most effective intervention, especially resistance exercises. Nutritional in-tervention has a low level of evidence. Objectives: The objective of this article is to review data on the effect of physical exercise in the treatment of sarcopenia. Method: Reviews and systematic re-views were searched in different data sources, including PubMed, between the years 2010 and 2024, with the keywords (sarcopenia and non-pharmacological treatment; sarcopenia and exercise and sarcopenia). Conclusions: Physical exercise is the first-line treatment for sarcopenia. There is no drug released for the specific treatment of sarcopenia, and nutritional interventions have little clinical evidence in improving the quantitative and functional aspects of the muscular system in sarcopenic patients. Among the exercise modalities, resistive exercises alone showed the most sig-nificant benefit in the muscular rehabilitation of sarcopenic patients. Despite this, when evaluated with resistive exercise, aerobic and balance exercises brought additional benefits in some muscular functions. Nutritional intervention also appears to improve muscle strength when associated with resistive exercises. More studies are needed to elucidate the best physical activity program and whether other nutritional interventions could benefit the patient more.

Antiviral Drugs for Treatment of Human Monkeypox: A Systematic Review/Meta-analysis

Background. On 23 July 2022, the World Health Organization declared a Public Health Emergency of International Concern. Monkeypox is a zoonotic viral disease caused by the monkeypox virus that is transmitted from animals to humans or from human to human. To date, treatment for human monkeypox is mostly symptomatic, as there is no specific standard antiviral treatment. Persons with severe symptoms and signs, immunocompromised patients, children younger than 8 years, and pregnant individuals should be considered for specific antiviral treatment. Objective. This study aims to assess effectiveness of antiviral drugs in treatment of human monkeypox. Methodology. Published clinical trials and cohort studies on the role of antivirals in the management of human monkeypox that were identified through a comprehensive search of electronic databases up to April 1, 2023. The patients included were children and adults confirmed with monkeypox. The diagnosis was based on PCR or clinical symptoms. The intervention was antivirals administration in human monkeypox patients, versus supportive treatment/placebo. Outcome measured include the duration of monkeypox until recovery, need for hospitalization, and ICU admission. Results. We included four completed studies with 195 participants assessing the safety, pharmacokinetics, and efficacy of antiviral treatments for human monkeypox compared to placebo. Three studies investigated Tecovirimat (st-246), and one investigated Brincidofovir. Both drugs were safe, tolerable, and effective with no serious adverse effects. The other 5 studies were not completed and are ongoing. Conclusion. There are currently no approved antivirals for the treatment of monkeypox; some medications could be authorized for outbreak use and are now under investigation, such as Tecovirimat, Cidofovir, and Brincidofovir.

Females show worse functional outcome and quality of life compared to males 2 years after meniscus surgery:Data analysis from the German Arthroscopy Registry.

The purpose of this study was to investigate the impact of sex on knee function, activity and quality of life following meniscus surgery using data from the German Arthroscopy Registry. This is a retrospective cohort study with data collected between 2017 and 2022. Patient-reported outcome measures (PROMs), namely Knee Injury and Osteoarthritis Outcome Score (KOOS), EuroQol Visual Analogue Scale (EQ Scale), and Marx Activity Rating Scale (MARS), were collected preoperatively and at 6, 12and 24 months postoperatively. Data were analysed to examine differences between male and female patients regarding PROMs, pre-existing conditions, meniscus lesion typesand surgical treatments. A total of 1106 female (36.6%) and 1945 male patients (63.7%) were included. Males were significantly younger than females and had a higher body mass index. Overall, there were four times more medial meniscus lesions (MMLs) (77.5%) than lateral meniscus lesions (LMLs) (27.9%). Degenerative LMLs were more frequent in females, while traumatic LMLs were more common in males. Frequencies of traumatic and degenerative MMLs were similar among males and females. Males had higher absolute KOOS irrespective of treatment or meniscus lesion type. Meniscus repair resulted in similar improvements in ΔKOOS for both sexes, while meniscus resection exhibited higher absolute KOOS for males at each time point. Males generally had higher EQ Scale and MARS than females. Greater improvements in knee function, activity and quality of life were observed in males. While MMLs appear to be comparable among sexes, the nature of LML differed significantly. These results may help surgeons to refine patient selection for specific treatments to improve overall clinical outcomes. Level III.

Prosthetic Rehabilitation of Post Covid Mucormycosis of Maxilla with Definitive Obturator Prosthesis- A 24 Month Follow Up Case Report

The second wave of COVID-19 in April 2021 witnessed a new mutated variant of SARS-CoV2 known as B.1.617 resulting in Mucormycosis. Inhalation, ingestion, or contamination of ulcerated mucosa by fungal spores results in infection and cause Mucormycosis. Objective: To highlight how a complex case of oral mucormycosis can be misdiagnosed due to its similar clinical presentations with other periodontal diseases and benefits of prosthetic rehabilitation of surgical defects with definitive obturator which improves the quality of life by restoring oral function and aesthetics. Case report: A 35-year-old female reported with chief complaint of pain, pus and mobility in upper front teeth region of 2 months and swelling of mid-face. Darkening of skin, swelling with tenderness over bilateral malar- infraorbital regions with epiphora and blurred vision in right eye and discharge from right nostril. She had multiple abscess in attached gingiva in incisor and premolar region of maxilla having probing depths ≤ 4mm with mobility. Conclusion: A precise diagnosis is prerequisite to specific treatment of any disease. Treatment often requires an extensive surgical resection causing facial deformation, masticatory, swallowing and speech problems. It is important to rehabilitate these patients by correcting the defects with the help of obturators and improve their lifestyle.

Current therapeutic targets and promising strategies for triple-negative breast cancer

TNBC refers to breast cancer patients with negative estrogen receptor ER, PR and HER-2. It accounts for about 1520% of all breast cancer cases and has a higher rate of disease recurrence and a worse prognosis than other breast cancer subtypes. Chemotherapy is the most effective treatment now available for TNBC, but it has major adverse consequences on human health. Therefore, the development of new TNBC treatment strategies has become an urgent clinical need. This article first starts with the different subtypes of TNBC, analyzes and summarizes the pathogenesis of TNBC and recent research progress. Secondly, the potential targets of TNBC and the development of targeted treatments based on these targets are analyzed. Finally, it is concluded that it is easier to achieve curative effect by using appropriate specific treatments for different subtypes of TNBC. By summarizing existing treatment regimens and their applicable TNBC subtypes, this article aims to provide new insights for follow-up treatment.

Nipah Virus Disease: An Updated Review

The Nipah virus (NiV) is a member of the Paramyxoviridae family of zoonotic viruses that is extremely contagious and potentially fatal. The Nipah virus was first discovered in 1999 during an outbreak in Malaysia. Since then, it has periodically caused outbreaks throughout South and Southeast Asia, especially in Bangladesh and India, and it continues to be a serious public health concern. The virus is primarily transmitted to humans through direct contact with infected fruit bats, which serve as natural reservoir hosts for the Nipah virus. Human-to-human transmission can also happen when infected people's body fluids come into close contact with one another. The Nipah virus has a high death rate that varies depending on the outbreak and can cause a variety of clinical presentations, including encephalitis, severe respiratory illnesses, and asymptomatic infections. Fever, headache, dizziness, drowsiness, and confusion are common signs of Nipah virus infections, which may lead to the rapid onset of coma in the patient. The Nipah virus does not presently have a specific antiviral treatment; instead, infection control methods and supportive care are the foundation of management to stop the virus from spreading. Nipah virus outbreaks must be stopped with an approach that includes community involvement, public health education, and surveillance of both human and animal populations. Additionally, efforts are directed toward developing vaccines as a more potent form of prevention. The Nipah virus is a clear reminder of the continuous threat that newly emerging infectious diseases pose, as well as the necessity of having strong surveillance systems and quick response times in place to lessen the effects that these outbreaks have on public health.

The Use of Coagulation–Flocculation for Industrial Colored Wastewater Treatment—(I) The Application of Hybrid Materials

Polluting species released in industrial-colored effluents contaminate water, degrading its quality and persisting in the aquatic environment; therefore, it must be treated for safe discharge or onsite reuse/recycling to ensure a fresh water supply. This review has the principal goal of facilitating understanding of some important issues concerning wastewater (WW) treatment systems, mainly based on a coagulation–flocculation step, as follows: (i) the significance of and facilities offered by specialized treatment processes, including the coagulation–flocculation step as a single or associated step (i.e., coagulation–flocculation followed by sedimentation/filtration or air flotation); (ii) the characteristics of industrial-colored WW, especially WW from the textile industry, which can be reduced via the coagulation–flocculation step; (iii) primary and secondary groups of hybrid materials and their characteristics when used as coagulants–flocculants; (iv) the influence of different process operating variables and treatment regimens on the efficiency of the studied treatment step; and (v) the benefits of using hybrid materials in colored WW treatment processes and its future development perspectives. The consulted scientific reports underline the benefits of applying hybrid materials as coagulants–flocculants in colored textile WW treatment, mainly fresh, natural hybrid materials that can achieve high removal rates, e.g., dye and color removal of >80%, heavy metals, COD and BOD of >50%, or turbidity removal of >90%. All of the reported data underline the feasibility of using these materials for the removal of colored polluting species (especially dyes) from industrial effluents and the possibility of selecting the adequate one for a specific WW treatment system.

Elucidating the molecular mechanisms of sepsis: Identifying key aging-related biomarkers and potential therapeutic targets in the treatment of sepsis.

Sepsis remains a crucial global health issue characterized by high mortality rates and a lack of specific treatments. This study aimed to elucidate the molecular mechanisms underlying sepsis and to identify potential therapeutic targets and compounds. High-throughput sequencing data from the GEO database (GSE26440 as the training set and GSE13904 and GSE32707 as the validation sets), weighted gene co-expression network analysis (WGCNA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, alongside a combination of PPI and machine learning methods (LASSO and SVM) were utilized. WGCNA identified the black module as positively correlated, and the green module as negatively correlated with sepsis. Further intersections of these module genes with age-related genes yielded 57 sepsis-related genes. GO and KEGG pathway enrichment analysis, PPI, LASSO, and SVM selected six hub aging-related genes: BCL6, FOS, ETS1, ETS2, MAPK14, and MYC. A diagnostic model was constructed based on these six core genes, presenting commendable performance in both the training and validation sets. Notably, ETS1 demonstrated significant differential expression between mild and severe sepsis, indicating its potential as a biomarker of severity. Furthermore, immune infiltration analysis of these six core genes revealed their correlation with most immune cells and immune-related pathways. Additionally, compounds were identified in the traditional Chinese medicine Danshen, which upon further analysis, revealed 354 potential target proteins. GO and KEGG enrichment analysis of these targets indicated a primary enrichment in inflammation and immune-related pathways. A Venn diagram intersects these target proteins, and our aforementioned six core genes yielded three common genes, suggesting the potential efficacy of Danshen in sepsis treatment through these genes. This study highlights the pivotal roles of age-related genes in the molecular mechanisms of sepsis, offers potential biomarkers, and identifies promising therapeutic compounds, laying a robust foundation for future studies on the treatment of sepsis.

Strangers "par excellence". Arabs in the Neo-Assyrian Royal Inscriptions

The basic questions posed in the article were: what characteristics caused Arabs to be per­ceived by the elites of the Neo-Assyrian Empire as strangers, and whether such classification resulted in their treatment differently from other peoples? Neo-Assyrian royal inscriptions and correspondence with the court were analysed to answer these questions. On this basis, three features that together are unique only to Arabs were distinguished: nomadism, camel farming and the presence of queens. These traits are unique to Arabs, so they are strangers par excellence from Assyria’s perspective. Interestingly, these features generally do not result in exceptional treatment. Only in a situation of conflict and defeat of the Arabs can one perceive their specific treatment, marked by exceptional cruelty even for Assyrians. For example, mainly Arab rulers were chained along with wild animals to the gates of the Assyrian capital. Moreover, only Arab women were subjected to tearing unborn children out of their wombs. This shows that Arabs were treated as half-humans against whom the most heinous crimes could be committed because Assyrians were not bound by the standards applicable to other peoples.

(100) Cavernovenous Leakage: A New Surgical Treatment in 171 Consecutive Patients with Severe, Drug-Resistant Erectile Dysfunction

Abstract Introduction Cavernovenous leakage (CVL) is a frequent cause of erectile dysfunction (ED) in which blood entering corpora cavernosa escapes too early due to abnormal venous network, for erections to develop or maintain. When PDE5Is are ineffective to compensate for leakage, CVL is a devastating condition, affecting millions worldwide for whom no specific treatment is currently proposed. Objective Evaluate results of a new method of treatment combining open surgery and embolization simultaneously during the same procedure, in patients with CVL resistant to PDE5Is. Methods 171 consecutive patients with severe ED for more than six months, with CVL diagnosed by pharmacologically-challenge penile duplex sonography (PC-PDS) using intracavernous injection of Prostaglandin E1 and Papaverine, were operated-on. Leaks were imaged by caverno-computed tomography. Patient with other cause of ED were excluded, all had refused a penile implant, signed an informed consent, had a control PC-PDS three months after surgery, and were clinically evaluated during follow-up. A retrospective analysis was performed on prospectively collected data. Comparisons of variables before and after surgery used a paired t-test. Results Mean age was 43.8±13.6 years, range 18–76. ED had started at the beginning of sexual life (30) in 47.4%. Mean ED duration before surgery was 11.1±9.1 years (range 0.5–30). All patients had two clinical signs of organic ED: 1. no phase of erection improvement in the past six months, 2. erection alterations during masturbation (Erection Hardness Score (EHS)<3 and/or erection instability). Signs suggesting CVL were 1. variation of erection hardness according to position during masturbations or intercourses in 59.1%, 2. erections instability during masturbation or intercourse in all patients. At three-month evaluation, mean pharmacologic EHS had increased from 2.56±.66 before surgery, to 3.40±.56 (p<.0001). All CVL hemodynamic parameters at PC-PDS had decreased compared to pre-surgery: mean End Diastolic Velocity (from 16.6±9.5 to 9.3±7.7 cm/s, p<.0001), mean leakage speed on Deep Dorsal Vein (from 12.8±13.4 to .8±3.2 cm/s, p<.0001), mean speed on any superficial vein (from 11.2±10.1 to 3.9±6.3 cm/s, p<.0001). Patients unable to perform penetrations despite ICC injection of Prostaglandin E1 20 micg plus Papaverine 40 mg (EHS<3) decreased from 66.9 to 11.6% (p<.001). At the end of the 29.8±20.4-month follow-up, IIEF-5 score had increased from 9.7±5.1 to 15.5±6.0 (p<.0001), clinical EHS during sexual intercourse from 2.0±.7 to 3.3±.7 (p<.0001), penetration success rate from 22.3±31,7 to 70.1±37.2% (p<.0001), mean EHS during masturbation from 2.11±.67 to 3.04±.75 (p<.0001), EHS at morning erection from .95±1.24 to 2.1±1.37 (p<.0001), before and after surgery, respectively. 30.4% did not take any medication for erection. Success rate defined by post-operative EHS>3 and/or EHS increase >0.5 and erection stability was 80.7%. 78.9% recognized sexual support by a sexual medicine specialist is necessary for sexual recovery after surgery. Conclusions Simultaneous open surgery and embolization is a new procedure that offers unprecedented documented results in CVL resistant to PDE5Is. Clinical screening of CVL in ED patients is simple and should be evaluated in sexual medicine practice. Disclosure No.

The utility of exome sequencing in diagnosing pediatric neurodevelopmental disorders in a highly consanguineous population.

Exome sequencing (ES) has been utilized in diagnosing children with neurodevelopmental manifestations, this study aimed to investigate the utility of ES in children within a highly consanguineous population that presented with neurodevelopmental complaints. A retrospective chart review was performed for 405 children with neurodevelopmental complaints who have had ES and were evaluated in multiple centers in the United Arab Emirates over a four-year period. Within the cohort of 405 children, consanguinity was reported in 35% (144/405). The primary clinical presentations were developmental delay/cognitive impairment, distinctive facial features, hypotonia, seizures, and weakness. The diagnostic yield was 57% (231/405). Novel variants were identified in 54% (125/231) of positive cases. Within the positive cases, specific treatment was available in 6% (13/231) and copy number variants (CNV) were reported in 3% (8/231) of cases. In eight children, variants in genes that have not yet been linked to human disease that could potentially be the cause of the observed phenotype "candidate genes" were identified. ES was utilized effectively within this cohort with a high diagnostic yield and through the identification of novel gene variants, CNVs, candidate genes and secondary findings as well as the alteration of the treatment plan in cases where treatment was available.

(157) Primary Erectile Dysfunction Caused by Cavernovenous Leakage: Clinical Presentation and New Surgical Treatment in 81 Consecutive Patients with Severe Erectile Dysfunction

Abstract Introduction Introduction. Primary erectile dysfunction (PED) due to cavernovenous leakage (CVL), a disease in which blood entering corpora cavernosa escapes too early because of abnormal venous network, may affect as many as 1 to 2% of men under 30 with failure of erections to develop or maintain. When resistant to PDE5Is, it is a devastating condition leaving men with no possibility of sexual intercourse with penetration, and usually absence of diagnosis and specific treatment. Objective Evaluate symptoms and results of a new method of treatment combining open surgery and embolization simultaneously during the same procedure, in patients with PED and CVL resistant to PDE5Is. Methods 81 consecutive patients with severe PED with CVL diagnosed by pharmacologically-challenge penile duplex sonography (PC-PDS) were operated-on. Leaks were imaged by caverno-computed tomography. Patients with other cause of ED were excluded, all had refused a penile implant, signed an informed consent, had a control PC-PDS three months after surgery, and were clinically evaluated during follow-up. A retrospective analysis was performed on prospectively collected data. Comparisons of variables before and after surgery used a paired t-test. Results Mean age at PED onset reported by patients was 19.0±4.6 years, range 13–30. Mean age at surgery was 34.5±9.2 years, range 18–70. Mean ED duration before surgery was 15.4±10.1 years (range 1–40). All patients had clinical signs of organic ED (no phase of erection improvement in the past six months, erectile dysfunction during masturbation (Erection Hardness Score (EHS)<3 and/or erection instability). CVL could be suspected in all patients based on reported erection instability during masturbation, and in 86.4%, based on variation of EHS according to body position during masturbations. At three-month evaluation, mean pharmacologic EHS had increased from 2.59±.77 before surgery, to 3.45±.63 (p<.0001). The mean pharmacologic EHS increase was 0.83±.92. All CVL hemodynamic parameters at PC-PDS had decreased compared to pre-surgery: mean End Diastolic Velocity (from 9.9±9.22 to 6.77±7.34 cm/s, p<.023), mean leakage speed on Deep Dorsal Vein (from 10.87±12.48 to .69±2.77 cm/s, p<.0001), mean speed on any superficial vein (from 10.96±10.08 to 4.77±6.90 cm/s, p<.0001). Patients unable to perform penetrations despite intracavernous injection of Prostaglandin E1 20 micg plus Papaverine 40 mg (pharmacological EHS<3) decreased from 64.2 to 13.5% (Chi-square test: p<.001). At the end of the 26.0±21.9-month follow-up, IIEF-5 score had increased from 8.9±5.3 to 16.1±5.8 (p<.013), clinical EHS during sexual intercourse from 1.97±.67 to 3.31±.71 (p<.0001), penetration success rate from 18.3±28.2 to 64.2±40.1%, morning EHSfrom 1.11±1.40 to 2.12±1.49 (p<.0002), masturbation EHS from 2.14±.84 to 3.07±.77 (p<.002) before and after surgery, respectively. 38.3% did not take any medication for erection. Conclusions Simultaneous open surgery and embolization is a conservative treatment that should be discussed for patients with PED and CVL. PED can be suspected during consultation. Detection of CVL in all patients under 30 with ED should be evaluated in sexual medicine practice. Disclosure No.

Nocturia in Menopausal Women: The Link Between Two Common Problems of the Middle Age.

The aim of this review is to discuss the link between menopause and nocturia and to give an overview of the increasing prevalence, risk factors, causative factors, treatment needs and options for nocturia in peri-menopausal women. This opinion article is a narrative review based on the expertise and consensus of a variety of key opinion leaders, in combination with an extensive literature review.This literature search included a thorough analysis of potential publications on both the PubMed Database and the Web of Science and was conducted between November 2022 and December 2022. The following key words were used "nocturia" and "menopause" or "nocturnal frequency and menopause." Moreover, key words including "incidence," "prevalence," "insomnia," "estrogen therapy," "metabolic syndrome," and "hot flushes" were used in combination with the aforementioned key words. Last, the reference lists of articles obtained were screened for other relevant literature. The perimenopause can be a trigger for inducing nocturia. Typically, obesity, body mass index (BMI), and waist circumference are risk factors for developing peri-menopausal nocturia. Presumably the development of peri-menopausal nocturia is multifactorial, with interplay among bladder, sleep, and kidney problems due to estrogen depletion after the menopause. First, impaired stimulation of estrogen receptors in the urogenital region leads to vaginal atrophy and reduced bladder capacity. Moreover, menopause is associated with an increased incidence of overactive bladder syndrome. Second, estrogen deficiency can induce salt and water diuresis through blunted circadian rhythms for the secretion of antidiuretic hormone and the activation of the renin-angiotensin-aldosterone system. Additionally, an increased incidence of sleep disorders, including vasomotor symptoms and obstructive sleep apnea signs, is observed. Oral dryness and a consequent higher fluid intake are common peri-menopausal symptoms. Higher insulin resistance and a higher risk of cardiovascular diseases may provoke nocturia. Given the impact of nocturia on general health and quality of life, bothersome nocturia should be treated. Initially, behavioral therapy should be advised. If these modifications are inadequate, specific treatment should be proposed. Systemic hormone replacement is found to have a beneficial effect on nocturia, without influencing sodium and water clearance in patients with nocturnal polyuria. It is presumed that the improvement in nocturia from hormonal treatment is due to an improvement in sleep disorders.

(003) Taking a Step Back for a (Future) Step Forward: Latent Class Analyses of Vulvo-Vaginal Pain Symptoms

Abstract Introduction Persistent genital pain represents a significant health issue among females, with prevalence ranging from 18.5% for lower genital tract discomfort [2], 20% for chronic dyspareunia [3], and 8.3%-27.9% for vulvodynia [6, 7]. Latent class analyses (LCA) allow the identification of groups of individuals who share common symptom profiles and have been used to subgroup vulvodynia patients based on psychological distress and pain sensitivity [1], spontaneous vs provoked pain and pain comorbidities [8] and based only on comorbid pain conditions [5]. Nonetheless, to our knowledge no study has been conducted investigating clusters of symptom-types commonly reported for persistent genital pain. Objective Test for latent classes (clusters) of individuals based on symptom-types profiles among women with vulvar and/or vaginal pain. Methods Self-reports on sexual and genital health were collected from 2199 women through online questionnaires, as part of a larger study. Efforts were made to recruit a heterogenous sample, with an oversampling of females with genito-pelvic pain. Participants were asked about the presence of specific vulvo-vaginal symptoms. Specifically, eight types of vulvar pain (itching, burning, irritation, needles, cut, electric-shock, bladder weight and urinary urgency) and nine types of vaginal pain (dryness, itching, burning, pulsating, needles, cut, electric shocks, spontaneous spasms and spasms at penetration) were measured. LCA were conducted to identify clusters of individuals sharing similar symptom profiles. Analyses were first done including all women with genital pain, then separately for women experiencing only vaginal and only vulvar pain. Results Of the 2199 participants, 1116 (51%) reported experiencing some type of genital pain, with 52% experiencing vulvar and vaginal pain, 17% only vaginal pain and 31% only vulvar pain. Results from LCA analyses suggest that women experiencing vulvo-vaginal pain could best be grouped into 5 clusters, based on the presence of vulvar and vaginal symptoms (Figure 1). Women with only vaginal pain were grouped into 3 clusters based on vaginal symptoms (Figure 2) and women with only vulvar pain were grouped into 3 clusters based on vulvar symptoms (Figure 3). Across all sets of analyses, clusters were clearly differentiated by specific symptoms. Conclusions Although rates of genital pain are high among females, classification of genito-pelvic pain conditions have been, and still are, a matter of debate. While in the DSM-5 vaginismus and dyspareunia were combined into one diagnostic entity, many clinicians continue referring to them as two distinct conditions, creating incoherence in terminology. In addition, chronic vulvar pain (or Vulvodynia) remains often undiagnosed [7], with women waiting an average of a 6-years before receiving a diagnosis [4]. Our data, obtained from a large sample, allowed us to identify profiles based on an empirical/data driven strategy, and provides an innovative approach to defining genital pain conditions. These results offer a starting point to re-think and discuss how diagnoses currently used to categorize female vulvo-vaginal pain can be improved. Longitudinal studies should be conducted to test whether the current strategy of grouping women with vulvo-vaginal pain provides improved diagnoses, more accurate prognoses, or improves our ability to identify patients who will or will not respond to specific treatments. Disclosure No.

Room-temperature polymorphism of a benzene-1,4-dicarboxamide liquid crystal: Hydrogen-bonded polar columnar assembly

Polymorphism is a fascinating research subject as it enables diverse functionalities to be achieved from a single molecule. In this study, we present the synthesis and polymorphic behavior of a liquid crystalline (LC) benzene-1,4-dicarboxamide (BDA) derivative (1). Depending on specific thermal treatments, two distinct polymorphs can be obtained at room temperature. These include a metastable glassy columnar (Colgla) and thermodynamically stable monoclinic crystalline (Cry) phases. Through the electric analysis, the Colgla polymorph exhibits a significant piezoelectric response, while the Cry polymorph shows a negligible piezoelectric signal. Notably, the BDA molecule exhibits an 81-helix columnar assembly (Colhel) in the LC phase, comprising syn-conformers with non-zero dipole moments. According to density functional theory (DFT) calculations, the amide group is tilted by 25° with respect to the central benzene ring. The piezoelectric response of the Colhel is comparable to that of the Colgla polymorph. Therefore, it can be inferred that the polar character of the Colgla polymorph is transferred from the Colhel LC phase during the cooling process. Simulation and spectroscopic analyses further reveal that the axial polarizations of both the Colgla and Colhel are driven by the hydrogen-bonding interactions between adjacent amide units in head-to-tail. These findings shed light on the underlying mechanisms of the polymorphic behavior and piezoelectric properties exhibited by the BDA molecule.

Stuck Behind the Times: How Current Controversies Related to Domestic Violence Intervention Programs are Addressed in U.S. State-Specific Documents

ABSTRACT This research assesses the extent to which current treatment-related controversies are addressed in state documents related to Domestic Violence Intervention Programs (DVIP). Specifically, we consider state-specific guidance on conducting treatment with female-identifying perpetrators, perpetrators in LGBTQ+ relationships, perpetrators located within relationships with bi-directional violence and perpetrators with a trauma history. Relevant DVIP governing documents were obtained from all U.S. states, as available (n = 47, 94%). Documents were coded with good interrater reliability (IRR = 82.4%). Although most states have gender-neutral or gender-non-specified DVIP guidelines (n = 31, 66%), 16 states (24%) have documents that specify they can only be applied to male perpetrators. Only two states (4%) provide detailed guidance for work with LGBTQ+ perpetrators. Of note, 44% of states (n = 22) exclude addressing bidirectional violence within their programs, despite its prevalence among violent couples. Only one state currently advises its DVIPs to assess for bidirectional violence at intake. While a substantial minority of states (n = 20, 40%) advise DVIPs to assess for perpetrator trauma, only a few state documents specifically endorse a trauma-informed approach (n = 6, 12%) even fewer require DVIP facilitators to include trauma information in their curriculum (n = 2, 4%). Problematically, many states’ DVIP guidelines have not been updated recently, with only 17 states having guidelines updated in the last five years. State policies must address the needs, motivations, and experiences of all DVIP perpetrators by acknowledging violence-related dynamics, incorporating a strength-based perspective, providing trauma-informed care, and enacting gender and LGBTQ±specific treatment recommendations.

Thickness and design features of clinical cranial implants-what should automated methods strive to replicate?

New deep learning and statistical shape modelling approaches aim to automate the design process for patient-specific cranial implants, as highlighted by the MICCAI AutoImplant Challenges. To ensure applicability, it is important to determine if the training data used in developing these algorithms represent the geometry of implants designed for clinical use. Calavera Surgical Design provided a dataset of 206 post-craniectomy skull geometries and their clinically used implants. The MUG500+ dataset includes 29 post-craniectomy skull geometries and implants designed for automating design. For both implant and skull shapes, the inner and outer cortical surfaces were segmented, and the thickness between them was measured. For the implants, a 'rim' was defined that transitions from the repaired defect to the surrounding skull. For unilateral defect cases, skull implants were mirrored to the contra-lateral side and thickness differences were quantified. The average thickness of the clinically used implants was 6.0 ± 0.5mm, which approximates the thickness on the contra-lateral side of the skull (relative difference of -0.3 ± 1.4mm). The average thickness of the MUG500+ implants was 2.9 ± 1.0mm, significantly thinner than the intact skull thickness (relative difference of 2.9 ± 1.2mm). Rim transitions in the clinical implants (average width of 8.3 ± 3.4mm) were used to cap and create a smooth boundary with the skull. For implant modelers or manufacturers, this shape analysis quantified differences of cranial implants (thickness, rim width, surface area, and volume) to help guide future automated design algorithms. After skull completion, a thicker implant can be more versatile for cases involving muscle hollowing or thin skulls, and wider rims can smooth over the defect margins to provide more stability. For clinicians, the differing measurements and implant designs can help inform the options available for their patient specific treatment.

Sheep-associated malignant catarrhal fever in cattle: an update

Sheep-associated malignant catarrhal fever (SA-MCF) is a frequently fatal disease of many species including cattle, caused by ovine herpes virus-2. Sheep are the main reservoir host species and transmit the virus to other species, usually via aerosol. Clinical signs in affected animals can impact various body systems, and infection can be sub-clinical and become latent. No specific treatments exist, and empirical treatments are generally unrewarding. Occasionally some animals may survive, but there remains a chronic arteriopathy. Currently, the disease is controlled on farms is by reducing contact between susceptible hosts and sheep as much as possible, although a vaccine would be a useful protective strategy should one be developed.

Mitochondrial ferritin alleviates ferroptosis in a kainic acid-induced mouse epilepsy model by regulating iron homeostasis: Involvement of nuclear factor erythroid 2-related factor 2.

Epilepsy is a widespread and chronic disease of the central nervous system caused by a variety of factors. Mitochondrial ferritin (FtMt) refers to ferritin located within the mitochondria that may protect neurons against oxidative stress by binding excess free iron ions in the cytoplasm. However, the potential role of FtMt in epilepsy remains unclear. We aimed to investigate whether FtMt and its related mechanisms can regulate epilepsy by modulating ferroptosis. Three weeks after injection of adeno-associated virus (AAV) in the skull of adult male C57BL/6 mice, kainic acid (KA) was injected into the hippocampus to induce seizures. Primary hippocampal neurons were transfected with siRNA using a glutamate-mediated epilepsy model. After specific treatments, Western blot analysis, immunofluorescence, EEG recording, transmission electron microscopy, iron staining, silver staining, and Nissl staining were performed. At different time points after KA injection, the expression of FtMt protein in the hippocampus of mice showed varying degrees of increase. Knockdown of the FtMt gene by AAV resulted in an increase in intracellular free iron levels and a decrease in the function of iron transport-related proteins, promoting neuronal ferroptosis and exacerbating epileptic brain activity in the hippocampus of seizure mice. Additionally, increasing the expression level of FtMt protein was achieved by AAV-mediated upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) gene in the hippocampus of seizure mice. In epilepsy, Nrf2 modulates ferroptosis by involving the expression of FtMt and may be a potential therapeutic mechanism of neuronal injury after epilepsy. Targeting this relevant process for treatment may be a therapeutic strategy to prevent epilepsy.

Ultrasound findings and specific intrinsic blood volume expansion therapy for neonatal capillary leak syndrome: report from a multicenter prospective self-control study

ObjectiveCapillary leak syndrome (CLS) is characterized by severe systemic edema without specific treatment, resulting in a high mortality rate. This study investigated whether there is organ edema in neonatal CLS patients and specific treatment strategies to improve patient prognosis.MethodsThirty-seven newborns diagnosed with CLS were included in this study. (1) Routine point-of-care ultrasound (POCUS) was used to identify whether the patients had visceral edema or fluid collection. (2) All patients were treated with 3% NaCl intravenously, and the clinical manifestations, laboratory indices and outcomes were compared before and after treatment.Results(1) Diffuse severe edema was found in 92.0% of the patients. (2) The POCUS examination revealed that CLS patients exhibited significant visceral edema in addition to diffuse severe edema, which included pulmonary edema in 67.6%, cerebral edema in 37.8%, severe intestinal edema in 24.3%, severe myocardial edema in 8.1%, pericardial effusion in 5.4%, pleural effusion in 29.7% and peritoneal effusion in 18.9%. Two patients (5.45%) had only myocardial edema without other manifestations. (3) Before and after the intravenous injection of 3% NaCl, there were no significant differences in the serum sodium or potassium levels of CLS patients, while the hemoglobin and hematocrit levels were significantly lower after treatment (p < 0.01). Her plasma ALB concentration and arterial pressure returned to normal levels after the treatment was completed. (4) All the patients survived, and no side effects or complications were observed during or after treatment with 3% NaCl.Conclusions(1) In addition to diffuse severe edema, visceral edema and effusion are common and important clinical manifestations of neonatal CLS and need to be detected by routine POCUS. (2) The intravenous injection of 3% NaCl is a safe, effective and specific treatment strategy for neonatal CLS, with a survival rate of 100% and no adverse effects.