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Hepatitis E virus (HEV) is an important emerging pathogen producing significant morbidity in immunosuppressed patients. HEV has been detrimental to solid organ transplant (SOT) patients, cancer patients, and HIV-positive patients, where chronic HEV infections occur. Blood-borne transfusions and multiple cases of chronic HEV infection in transplant patients have been reported in the past few decades, necessitating research on HEV pathogenesis using immunosuppressed animal models. Numerous animal species with unique naturally occurring HEV strains have been found, several of which have the potential to spread to humans and to serve as pathogenesis models. Host immunosuppression leads to viral persistence and chronic HEV infection allows for genetic adaptation to the human host creating new strains with worse disease outcomes. Procedures necessary for SOT often entail blood transfusions placing immunosuppressive patients into a "high risk group" for HEV infection. This scenario requires an appropriate immunosuppressive animal model to understand disease patterns in these patients. Hence, this article reviews the recent advances in the immunosuppressed animal models for chronic HEV infection with emphasis on pathogenesis, immune correlates, and the liver pathology associated with the chronic HEV infections. [ABSTRACT FROM AUTHOR]

Alcohol misuse ranks among the leading causes of preventable death worldwide. Therefore, discovering measures that can predict hazardous drinking is critical. The delay discounting paradigm—which assesses relative preference for immediate rewards over larger, later rewards—has frequently been used as a proxy for impulsive choice, but it does not capture how long someone is willing to wait for delayed rewards when the arrival time is uncertain. In contrast, a newer willingness‐to‐wait task measures how long someone is willing to wait for a delayed reward of uncertain timing before giving up. We hypothesized that performance in this willingness‐to‐wait task would be associated with drinking severity and that this task may even outperform delay discounting as a predictor of drinking severity. We pooled data from multiple studies of mostly college‐aged adult participants. Drinking severity was assessed with the Alcohol Use Disorders Identification Test. Willingness to wait under temporal uncertainty, but not delay discounting, was associated with severity of alcohol problems among participants who drank (n = 212). Individuals engaging in hazardous drinking were less willing to wait for rewards when delays were unknown than were individuals with low‐risk drinking habits. Thus, willingness to wait under temporal uncertainty may be an important predictor of problematic drinking. [ABSTRACT FROM AUTHOR]

AbstractPurposeConclusionThe increasing amounts of ultraviolet-B (UV-B) light in our surroundings have sparked worries about the possible effects on humans and plants. The detrimental effects of heightened UV-B exposure on these two vital elements of terrestrial life are different due to their unique and concurrent nature. Understanding common vulnerabilities and distinctive adaptations of UV-B radiation by exploring the physiological and biochemical responses of plants and the effects on human health is of huge importance. The comparative effects of UV-B radiation on plants and animals, however, are poorly studied. This review sheds light on the sophisticated web of UV-B radiation effects by navigating the complex interaction between botanical and medical perspectives, drawing upon current findings.By providing a comprehensive understanding of the complex effects of heightened UV-B radiation on plants and humans, this study summarizes relevant adaptation strategies to the heightened UV-B radiation stress, which offer new approaches for improving human cellular resilience to environmental stressors. [ABSTRACT FROM AUTHOR]

Knowledge is needed regarding mechanisms acting between physical activity (PA) and chronic pain. We investigated whether cold pain tolerance mediates an effect of leisure-time physical activity on the risk of chronic pain 7 to 8 years later using consecutive surveys of the population-based Tromso Study. We included participants with information on baseline leisure-time PA (LTPA) and the level of cold pressor-assessed cold pain tolerance, who reported chronic pain status at follow-up as any of the following: chronic pain for ≥3 months, widespread chronic pain, moderate-to-severe chronic pain, or widespread moderate-to-severe chronic pain. We included 6834 participants (52% women; mean age, 55 years) in counterfactual mediation analyses. Prevalence decreased with severity, for example, 60% for chronic pain vs 5% for widespread moderate-to-severe chronic pain. People with one level higher LTPA rating (light to moderate or moderate to vigorous) at baseline had lower relative risk (RR) of 4 chronic pain states 7 to 8 years later. Total RR effect of a 1-level LTPA increase was 0.95 (0.91-1.00), that is, -5% decreased risk. Total effect RR for widespread chronic pain was 0.84 (0.73-0.97). Indirect effect for moderate-to-severe chronic pain was statistically significant at RR 0.993 (0.988-0.999); total effect RR was 0.91 (0.83-0.98). Statistically significantly mediated RR for widespread moderate-to-severe chronic pain was 0.988 (0.977-0.999); total effect RR was 0.77 (0.64-0.94). This shows small mediation of the effect of LTPA through pain tolerance on 2 moderate-to-severe chronic pain types. This suggests pain tolerance to be one possible mechanism through which PA modifies the risk of moderate-to-severe chronic pain types with and without widespread pain. [ABSTRACT FROM AUTHOR]

This study aimed to systematically review the effect of nitrate supplementation on blood oxygen saturation. We searched PubMed, Scopus, and Cochrane Library databases from their inception up to October 2022. Two reviewers independently conducted two stages of the screening process to include a randomized controlled trial with nitrate supplementation versus placebo intervention assessing oxygen saturation among lowlanders going to either real or simulated high altitude environments. We used the Cochrane Risk of Bias 2.0 tool to assess the risk of bias in the included studies. Fixed-effect model meta-analyses were conducted for laboratory-based studies. Random-effect meta-analyses were conducted for real-world studies. We found 7 trials that met the eligibility criteria. A meta-analysis of studies with some bias concerns showed an increase of 1.26 % in the SpO2 with 44 % I2 during submaximal exercise at simulated high altitudes (GRADE: low). On the contrary, a meta-analysis of studies without heterogeneity showed that nitrate supplementation aggravated oxygen saturation decline (−2.64 %, p = 0.03, GRADE: high) during rest in real high-altitude environments. A meta-analysis also showed that nitrate supplementation did not affect Acute Mountain Sickness (AMS) symptoms (GRADE: high). Our results suggest that nitrate supplementation did not provide benefits for AMS prevention during rest at high altitudes. The low-quality evidence showing small beneficial effects of nitrate supplementation during exercise calls for further studies. [ABSTRACT FROM AUTHOR]

Purpose: We hypothesised that during a rest-to-exercise transient in hypoxia (H), compared to normoxia (N), (i) the initial baroreflex sensitivity (BRS) decrease would be slower and (ii) the fast heart rate (HR) and cardiac output (CO) response would have smaller amplitude (A1) due to lower vagal activity in H than N. Methods: Ten participants performed three rest-to-50 W exercise transients on a cycle-ergometer in N (ambient air) and three in H (inspired fraction of O2 = 0.11). R-to-R interval (RRi, by electrocardiography) and blood pressure profile (by photo-plethysmography) were recorded non-invasively. Analysis of the latter provided mean arterial pressure (MAP) and stroke volume (SV). CO = HR·SV. BRS was calculated by modified sequence method. Results: Upon exercise onset in N, MAP fell to a minimum (MAPmin) then recovered. BRS decreased immediately from 14.7 ± 3.6 at rest to 7.0 ± 3.0 ms mmHg−1 at 50 W (p < 0.01). The first BRS sequence detected at 50 W was 8.9 ± 4.8 ms mmHg−1 (p < 0.05 vs. rest). In H, MAP showed several oscillations until reaching a new steady state. BRS decreased rapidly from 10.6 ± 2.8 at rest to 2.9 ± 1.5 ms mmHg−1 at 50 W (p < 0.01), as the first BRS sequence at 50 W was 5.8 ± 2.6 ms mmHg−1 (p < 0.01 vs. rest). CO-A1 was 2.96 ± 1.51 and 2.31 ± 0.94 l min−1 in N and H, respectively (p = 0.06). HR-A1 was 7.7 ± 4.6 and 7.1 ± 5.9 min−1 in N and H, respectively (p = 0.81). Conclusion: The immediate BRS decrease in H, coupled with similar rapid HR and CO responses, is compatible with a withdrawal of residual vagal activity in H associated with increased sympathetic drive. [ABSTRACT FROM AUTHOR]

Photon-counting detector CT (PCD-CT) is a new technology that has multiple diagnostic benefits including increased spatial resolution, iodine signal, and radiation dose efficiency, as well as multi-energy imaging capability, but which also has unique challenges in abdominal imaging. The purpose of this work is to summarize key features, technical parameters, and terms, which are common amongst current abdominopelvic PCD-CT systems and to propose standardized terminology (where none exists). In addition, user-selectable protocol parameters are highlighted to facilitate both scientific evaluation and early clinical adoption. Unique features of PCD-CT systems include photon-counting detectors themselves, energy thresholds and bins, and tube potential considerations for preserved spectral separation. Key parameters for describing different PCD-CT systems are reviewed and explained. While PCD-CT can generate multi-energy images like dual-energy CT, there are new types of images such as threshold images, energy bin images, and special spectral images. The standardized terms and concepts herein build upon prior interdisciplinary consensus and have been endorsed by the newly created Society of Abdominal Radiology Photon-counting CT Emerging Technology Commission. [ABSTRACT FROM AUTHOR]

Ultrasound is used for peripheral intravenous (PIV) cannulation in patients with difficult landmark-guided IV access in the Emergency Department. Distal-to-proximal application of an Esmarch bandage on the target limb has been suggested as a method for increasing vein size and ease of cannulation. This study was a single-blinded crossover randomized controlled trial comparing basilic vein size under ultrasound with use of an Esmarch bandage in addition to standard IV tourniquet ("tourniquet + Esmarch") compared to use of a standard IV tourniquet alone. Participant discomfort with the tourniquet + Esmarch was also compared to that with standard IV tourniquet alone. Twenty-two healthy volunteers were used to measure basilic vein size with and without the Esmarch bandage. There was no difference in basilic vein size between the two groups, with a mean diameter of 6.0 ± 1.5 mm in the tourniquet + Esmarch group and 6.0 ± 1.4 mm in the control group, p = 0.89. Discomfort score (from 0 to 10) was different between the groups, with a mean discomfort score of 2.1 in the tourniquet + Esmarch group and 1.1 in the standard IV tourniquet alone group (p < 0.001). This study showed that the use of an Esmarch bandage does not increase basilic vein size in healthy volunteers but is associated with a mild increase in discomfort. [ABSTRACT FROM AUTHOR]

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The benefit of the computer-aided design and manufacturing (CAD/CAM) technique for stand-alone genioplasty remains uncertain and was evaluated in this study. Patients who underwent a conventional genioplasty (n = 20) or genioplasty with the CAD/CAM technique (n = 20), and for whom cephalometry and photogrammetry were performed before and 6 months after surgery, were included. Deviations from predictions of the soft tissue pogonion (Pg′), lip inferior point to aesthetic line (Li–Esth), facial convexity angle (FCA), mentolabial angle (MLA), and ratios of soft to hard tissue movements were calculated. No significant deviation was observed for Pg′ in either the conventional group (3.85 ± 4.36 mm; 1.91 ± 1.11 mm) or CAD/CAM group (1.28 ± 1.16 mm; 2.81 ± 3.08 mm), for horizontal and vertical movements, respectively. However, for forward movement, deviation from the prediction of Pg´ in the CAD/CAM group was significantly lower than that in the conventional group (P = 0.015). Deviations of Li–Esth, MLA, and FCA did not differ significantly between the groups. No definite preference for the CAD/CAM technique could be established, because deviations from predictions were not significant in either of the technique groups and lay within the clinically acceptable range. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study was to examine the reliability and validity of a single lateral condyle-capsule distance (LCCD) measurement while saving on economic costs and clinical resources. Methods: A longitudinal test–retest design was used to assess the reliability and validity of single-examiner measures over 72 TMJ sonographic analyses. Intraclass correlation coefficients (ICC) and a Bland–Altman plot were used to study reliability and validity, comparing the first measurement of the LCCD to the mean of 3 measurements taken one week later by the same examiner. Results: ICC show intraobserver reliability of 0.981, 95% confidence intervals (CI) of 0.969 to 0.988. The mean difference between the ultrasound measurements is 0.019 mm (95% CI 0.0005–0.0383) with a standard deviation of 0.080 mm, demonstrating robust validity. The 95% Limits of Agreement (LoA) are − 0.138 for the lower limit and 0.177 for the upper. Mean relative error is 0.009 mm. Conclusion: Intraobserver reliability of a trained examiner is very high in the single measurement of the LCCD and validity is significant compared to more complex methods. The risk of bias is low since the mean of three LCCD measurements is calculated as opposed to recording only one single measurement. [ABSTRACT FROM AUTHOR]

Introduction: Primary hydatid cyst of the spinal cord is exceedingly rare. Diagnosis at the early stages is difficult as they may be asymptomatic or have mild vague pain. Patients typically present when there are features of cord/root compression. Magnetic resonance imaging (MRI) stands as the primary investigative modality, but even then, preoperative diagnosis might not always be possible as it may resemble other pathological conditions. Methods: This was a case report of a single case with evidence-based discussion. Informed consent was obtained. Case Report: We present a 62-year-old female patient with progressive paraparesis and numbness of bilateral lower limbs. MRI was suggestive of a tubercular pleurospinal lesion at the D9-D10 level. However, intraoperatively, it was identified to be a rare case of primary pleurospinal (thoracic) hydatid cyst. The patient was managed with complete surgical removal of all the cysts and antihelminthic drug therapy with no evidence of recurrence at the 2-year follow-up. Conclusion: Radiological diagnosis might not be accurate and hydatidosis must be kept in mind to avoid intraoperative confusion. Timely diagnosis, appropriate surgical planning, and comprehensive follow-up are crucial for achieving optimal outcomes. [ABSTRACT FROM AUTHOR]

Introduction High-grade serous ovarian cancer (HGSOC) is characterized by high mortality and prevalent recurrences. This study investigates the prognostic value of phosphoglycerate dehydrogenase (PHGDH) in HGSOC which has been linked to metabolic reprogramming and recurrences in other cancers. Methods Data from 306 patients with advanced-stage HGSOC treated between 2008 and 2015 were analyzed. PHGDH expression levels were determined using immunohistochemistry and categorized as "low" or "high." Results PHGDH-high was associated with higher FIGO stage and increased use of neoadjuvant chemotherapy. Patients with PHGDH-high tumors had significantly worse survival than PHDH-low, even after adjusting for confounding factors. [ABSTRACT FROM AUTHOR]

Lyme disease is a zoonotic infection due to Ixodes tick–transmitted Borrelia burgdorferi sensu lato spirochetes and the most common vector-borne disease in the Northern Hemisphere. Despite nearly 50 years of investigation, the pathogenesis of this infection and its 2 main adverse outcomes—postinfectious Lyme arthritis and posttreatment Lyme disease syndrome—are incompletely understood. Advancement in sequencing and mass spectrometry have led to the rapid expansion of high-throughput omics technologies, including transcriptomics, metabolomics, and proteomics, which are now being applied to human diseases. This review summarizes findings of omics studies conducted on blood and tissue samples of people with acute Lyme disease and its postinfectious outcomes. [ABSTRACT FROM AUTHOR]

Cellular senescence is a cell fate triggered in response to stress and is characterized by stable cell-cycle arrest and a hypersecretory state. It has diverse biological roles, ranging from tissue repair to chronic disease. The development of new tools to study senescence in vivo has paved the way for uncovering its physiological and pathological roles and testing senescent cells as a therapeutic target. However, the lack of specific and broadly applicable markers makes it difficult to identify and characterize senescent cells in tissues and living organisms. To address this, we provide practical guidelines called "minimum information for cellular senescence experimentation in vivo " (MICSE). It presents an overview of senescence markers in rodent tissues, transgenic models, non-mammalian systems, human tissues, and tumors and their use in the identification and specification of senescent cells. These guidelines provide a uniform, state-of-the-art, and accessible toolset to improve our understanding of cellular senescence in vivo. This primer introduces the "minimal information on cellular senescence experimentation in vivo " (MICSE) guidelines, which aim to address the challenges in identifying and characterizing senescent cells. It provides an overview of senescence markers in various systems and offers a practical toolset to enhance our understanding of cellular senescence in vivo. [ABSTRACT FROM AUTHOR]

Sex steroid hormones (SSH) are extremely versatile molecules with a myriad of physiological functions. Next to their well-known role in sexual development and reproduction, SSH play active roles in practically every tissue in the human body, including the oral cavity. It has long been demonstrated that periodontal tissues express SSH receptors and therefore are responsive to the presence of SSH. Interestingly, SSH not only interact with the periodontal tissues but also with other tissues in the oral cavity such as dental enamel, pulp, cementum, oral mucosa, and salivary glands. Questions concerning the possible physiological functions of these receptors and their role in maintenance of oral health, remain unanswered. The purpose of this scoping review was to gather and summarize all the available evidence on the role of SSH in physiological processes in the oral cavity in humans. Two comprehensive literature searches were performed. References were screened and selected based on title, abstract and full text according to our inclusion criteria. Both searches yielded 18,992 results of which 73 were included. Results were divided into four categories: (1) Periodontium; (2) Dental structure; (3) Mucosa; and (4) Salivary glands. The interaction of these tissues with progestagens, androgens and estrogens are summarized. Sex steroid hormones are an overlooked yet fundamental factor in oral homeostasis. They play important roles in the development and function of the periodontium, dental structure, mucosa and salivary glands. Dentists and healthcare providers should consider these hormonal factors when assessing and treating oral health conditions. [ABSTRACT FROM AUTHOR]

The ephemeral reward task involves providing subjects with a choice between two distinctive stimuli, A and B, each containing an identical reward. If A is chosen, the reward associated with A is obtained and the trial is over. If B is chosen, the reward associated with B is obtained but A remains, and the reward associated with A can be obtained as well. Thus, the reward-maximizing solution is to choose B first. Although cleaner fish (wrasse) and parrots easily acquire the optimal response by choosing B, paradoxically, several nonhuman primate species, as well as rats and pigeons, do not. It appears that some species do not associate their choice and reward with the second reward. Surprisingly, research in an operant context with pigeons and rats suggests that inserting a delay between the choice and reward facilitates optimal choice. It is suggested that impulsivity may be, in part, responsible for the difficulty of the task. In an attempt to better understand this task, we trained human subjects on an operant version of this task, with and without a brief delay between choice and reward and found that many subjects failed to learn to choose optimally, independent of the delay. Furthermore, performance on this task was not correlated with a task thought to measure impulsivity, the Balloon Analog Risk Task or with the Abbreviated Impulsivity Survey. We concluded that, for humans, the task is confusing because there is no incorrect response, only good and better, and better is not easily discriminated. [ABSTRACT FROM AUTHOR]

There is a growing number of studies investigating discriminatory fear conditioning and conditioned inhibition of fear to assess safety learning, in addition to extinction of cued fear. Despite all of these paradigms resulting in a reduction in fear expression, there are nuanced differences among them, which could be mediated through distinct behavioral and neural mechanisms. These differences could impact how we approach potential treatment options in clinical disorders with dysregulated fear responses. The objective of this review is to give an overview of the conditional discrimination and inhibition findings reported in both animal models and human neuropsychiatric disorders. Both behavioral and neural findings are reviewed among human and rodent studies that include conditional fear discrimination via conditional stimuli with and without reinforcement (CS+ vs. CS−, respectively) and/or conditional inhibition of fear through assessment of the fear response to a compound CS−/CS+ cue versus CS+. There are several parallels across species in behavioral fear expression as well as neural circuits promoting fear reduction in response to a CS− and/or CS−/CS+ compound cue. Continued and increased efforts to compare similar behavioral fear inhibition paradigms across species are needed to make breakthrough advances in our understanding and treatment approaches to individuals with fear disorders. [ABSTRACT FROM AUTHOR]

Background and Aim: Canine rabies is an endemic form of zoonosis and represents a major public health threat in Guinea, similar to other African countries. However, few investigations on the epidemiology of rabies in animals and humans have been conducted, and evidence-based data required to inform health policies remain inadequate. This study was conducted to update our knowledge of human dog-mediated rabies epidemiology and post-exposure prophylaxis (PEP) accessibilityrelated factors in Guinea. Materials and Methods: This retrospective study, conducted from January 2018 to December 2020, collected data on animal bite cases, veterinary observations, rabies diagnoses through fluorescent antibody test, and PEP delivery from three veterinary and medical entities. Statistical analysis utilized Chi-square test and Fisher's exact test to evaluate relationships between variables. Results: An average of 775 bites was recorded annually, and dogs were responsible for 98% of bites. However, only 64% of the biting dogs were under veterinary observation as required for integrated bite case management. Regarding the geographical distribution of bite cases, the entire country was affected, with the highest number of bites recorded in the prefectures of Nzérékoré and the special zone of Conakry. In addition, the laboratory diagnosis of brain samples from biting dogs indicated that 72% of the samples were rabies-positive. However, regarding prevention, only 58% of the bitten individuals received full PEP. Conclusion: Improving disease surveillance and PEP provision for dog-transmitted rabies is crucial to preventing human cases and deaths. Increasing community awareness is essential for enhancing dog vaccination and PEP utilization. A national action plan integrating stakeholders for controlling canine rabies should be developed for effective One Health collaboration. [ABSTRACT FROM AUTHOR]

The cerebellum, a major feature of the hindbrain, lies posterior to the pons and medulla and inferior to the posterior part of the cerebrum. It lies beneath the tentorium cerebelli in the posterior cranial fossa and consists of two lateral hemispheres connected by the vermis. The cerebellum is primarily supplied by three arteries originating from the vertebrobasilar system: the superior cerebellar artery (SCA), the anterior inferior cerebellar artery (AICA), and the posterior inferior cerebellar artery (PICA). However, variations of the cerebellar arteries may occur, such as duplication of the SCA, SCA creating a common trunk with the posterior cerebral artery, triplication of the AICA, and agenesis of PICA, amongst others. Knowledge of the arterial anatomy of the cerebellum is crucial, as inadequate blood supply to this region can result in diminished motor functioning, significantly impacting the quality of life for patients. The present study demonstrated the importance of adequate anatomical knowledge of the arteries supplying the cerebellum. The PubMed and Embase databases were searched to gather articles on the anatomical characteristics and variations of the arterial supply of the cerebellum. It is the most comprehensive and up-to-date review available in the literature. The possible variations of these vessels may be clinically silent or present with clinical symptoms such as neurovascular compression syndromes of the cranial nerves and aneurysms. With a comprehensive understanding of the cerebellar arterial system, physicians can enhance their diagnostic and treatment capabilities, ultimately leading to more effective management of cerebellar vascular-related issues and other neurological deficits. [ABSTRACT FROM AUTHOR]

Background: Ovarian granulosa cells (GCs) are essential for follicular development. Ovarian advanced glycation endproducts (AGEs) accumulation is related to GCs dysfunction. Alpha-lipoic acid (ALA) illustrates therapeutic capabilities for infertility-related disorders. Therefore, this study assessed the effects of ALA on AGEs-induced GCs hormonal dysfunction. Methods: The study was conducted from October 2021 to September 2022 at the Department of Medical Genetics, Shiraz University of Medical Sciences. Isolated GCs (n=50) were divided into control, human glycated albumin (HGA), HGA+ALA, and ALA treatments. Steroidogenic enzymes and AGE receptor (RAGE) genes were assessed by qRT-PCR. Steroid hormones and RAGE protein were evaluated using ELISA and Western blotting. Data were analyzed using GraphPad Prism software (ver. 9), and P<0.05 was considered significant. Results: Our findings showed that HGA treatment significantly (P=0.0001) increased RAGE (by 140.66%), STAR (by 117.65%), 3β-HSD (by 165.68%), and 17β-HSD (by 122.15%) expression, while it decreased CYP19A1 (by 68.37%) expression. RAGE protein level (by 267.10%) was also increased in HGA-treated GCs. A significant decrease in estradiol (by 59.66%) and a slight and sharp elevation in progesterone (by 30.40%) and total testosterone (by 158.24%) levels was also observed. ALA treatment ameliorated the HGA-induced changes in steroidogenic enzyme mRNA levels (P=0.001) and steroid hormone secretion (P=0.010). Conclusion: This work shows that ALA therapy likely corrects hormonal dysfunctions caused by AGEs in luteinized GCs. This effect is probably achieved by decreased RAGE expression. Clinical research is needed to understand how AGEs and ALA interact in the ovary, which might lead to a more targeted ovarian dysfunction therapy. [ABSTRACT FROM AUTHOR]

Background: Late-stage pressure sore (PS) patients are particularly susceptible to osteomyelitis (OM), as bony prominences commonly constitute the focal point of the ulcer. There are lack of data regarding the associated factors and the clinical relevance of this diagnosis in the context of PS treatment. Methods: This retrospective analysis investigated the clinical characteristics, blood markers indicative of infection in PS patients, and development of histologically evident OM. A total of 125 patient were included from 2014 to 2019. The patient records were especially scanned for histological diagnosis of OM. Results: OM was detected in 39% (37/96) of the samples taken during the index procedure. OM prevalence increased to 56% (43/77) at the second and 70% (41/59) at the third debridement. Therefore, the diagnosis of OM was acquired during treatment in 35 cases. Patients diagnosed with initial OM presented significantly higher blood markers, indicative of infection upon admission. Only patients with consistent OM (three positive biopsies) showed higher flap revision rates. Conclusion: This study found no compelling evidence linking OM to worse clinical outcomes in PS patients. In the absence of elevated inflammatory markers, reducing bone biopsy frequency and adopting a less aggressive bone debridement approach may help prevent OM in PS patients. [ABSTRACT FROM AUTHOR]

Despite significant advancements in ocular drug delivery, challenges persist in treating posterior segment diseases like macular edema (ME) and age-related macular degeneration (AMD). Suprachoroidal (SC) injections are a promising new method for targeted drug delivery to the posterior segment of the eye, providing direct access to the choroid and retina while minimizing systemic exposure and side effects. This review examines the anatomical and physiological foundations of the SC space; evaluates delivery devices such as microcatheters, hypodermic needles, and microneedles; and discusses pharmacokinetic principles. Additionally, advancements in gene delivery through SC injections are explored, emphasizing their potential to transform ocular disease management. This review also highlights clinical applications in treating macular edema, diabetic macular edema, age-related macular degeneration, choroidal melanoma, and glaucoma. Overall, SC injections are emerging as a promising novel route for administering ophthalmic treatments, with high bioavailability, reduced systemic exposure, and favorable safety profiles. Key therapeutic agents such as triamcinolone acetonide, dexamethasone, AAV-based gene therapy, and axitinib have shown promise. The field of suprachoroidal injection is progressing rapidly, and this review article, while attempting to encapsulate most of the published preclinical and clinical studies, mainly focuses on those that are published within 2023 and 2024. [ABSTRACT FROM AUTHOR]

Human African trypanosomiasis (HAT) in Nigeria is caused primarily by Trypanosoma brucei gambiense (gHAT), which has historically been a major human and animal health problem. This study aims to examine the status of gHAT in Nigeria over the past 60 years. The World Health Organization (WHO) set two targets to eliminate HAT as a public health concern by 2020 and terminate its global transmission by 2030. The former target has been achieved, but accurate monitoring and surveillance are important for maintaining this success and delivering the second target. Although recent cases in Nigeria are rare, accurately estimating the national seroprevalence and actual prevalence of gHATs remains challenging. To address this, a meta-analysis reviewed studies on gHATs in Nigeria from databases such as Embase, Global Health, Ovid Medline, Web of Science, and Google Scholar. Ten studies were included, ranging between 1962 and 2016, covering 52 clusters and 5,671,877 individuals, even though databases were scrutinized up to 2022. The seroprevalence ranged from 1.75 to 17.07%, with an overall estimate of 5.01% (95% CI 1.72–9.93). The actual gHAT prevalence detected by parasitological or PCR methods was 0.001 (95% CI 0.000–0.002), indicating a prevalence of 0.1%. Notably, the seroprevalence was greater in southern Nigeria than in northern Nigeria. These findings suggest that the disease might be spreading unnoticed due to the increased movement of people from endemic areas. This study highlights the paucity of studies in Nigeria over the last 60 years and emphasizes the need for further research, systematic surveillance, and proper reporting methods throughout the country. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Has there been variation in semen quality among men applying to be sperm donors (i.e. donor candidates) in Denmark in recent years (2017–2022)? SUMMARY ANSWER The motile sperm concentration and total motile sperm count (TMSC) in ejaculates—both measures of sperm quality—declined by as much as 22% from 2019 to 2022. WHAT IS KNOWN ALREADY Questions remain about whether human semen quality has declined in recent years. Whilst some studies provide evidence for a decline in human semen quality, these findings have been disputed owing to potential biases in the populations studied or in the methods used to measure semen quality. Resolution of this issue has important implications for human fertility, as well as for those involved in the recruitment of sperm donors for use in medically assisted reproduction. STUDY DESIGN, SIZE, DURATION We obtained data on the semen quality of ejaculates previously collected from 2017 to 2022 at sperm bank locations in four cities in Denmark: Aarhus, Aalborg, Copenhagen, and Odense. Our study focuses on the single semen samples provided by 6758 donor candidates aged between 18 and 45 years old to determine whether their sperm quality met a minimum criterion for them to be accepted as sperm donors. PARTICIPANTS/MATERIALS, SETTING, METHODS All ejaculates were analyzed within 1 hour of production. Semen volume (ml) was estimated by weight and both the concentration (106/ml) of sperm as well as the concentration of motile sperm (World Health Organization grades a and b) were measured using the same protocols and computer-assisted semen analysis system across all years at each site. Statistical analyses of the semen variables were controlled for age and donation site, as well as the average monthly high temperature when the ejaculate was produced. MAIN RESULTS AND THE ROLE OF CHANCE From 2017 to 2019, semen volume, sperm concentration, and total sperm count in the ejaculates of donor candidates increased by 2–12%. Then, from 2019 to 2022, sperm concentration and total sperm count changed by 0.1–5% from year to year, but none of those changes were statistically significant. In contrast, both motile sperm concentration and TMSC declined significantly, by 16% and 22%, respectively, between 2019 and 2022. Thus, the concentration of motile sperm in donor candidates declined from 18.4 [95% CL: 17.0, 20.0] million/ml in 2019 to 15.5 [14.4, 16.7] million/ml in 2022, and TMSC declined from 61.4 [55.8, 67.5] million per ejaculate in 2019 to 48.1 [44.1, 52.4] million in 2022. LIMITATIONS, REASONS FOR CAUTION We cannot determine from the available data the causes of the decline in semen quality of donor candidates from 2019 to 2022. However, as this period coincides with lockdowns and changes in work patterns during the coronavirus disease 2019 pandemic, it is possible that changes in motile sperm concentration and TMSC were the result of changes in the lifestyles of the men whose semen was analyzed. WIDER IMPLICATIONS OF THE FINDINGS Men providing initial semen samples at sperm banks, when applying to be sperm donors, are a useful population in which to monitor changes in human semen quality over time. Our results have implications for human fertility and the recruitment of sperm donors for medically assisted reproduction, where motile sperm concentration is an essential selection criterion because it influences fertility. We suggest that gathering health and lifestyle data on donor candidates at sperm banks might help to identify causal factors for the decline of sperm quality that could be addressed and intervention, if desired, could be personalized for each accepted donor. STUDY FUNDING/COMPETING INTEREST(S) No external funding was obtained for this study. E.L. and A.-B.S. are employees of Cryos International. AP reports paid consultancy for Cryos International, Cytoswim Ltd, Exceed Health, and Merck Serono in the last 2 years of this study, but all monies were paid to the University of Sheffield (former employer). AP is also an unpaid trustee of the Progress Educational Trust (Charity Number 1139856). RM declares support from Cryos International to present results of this research at ESHRE 2023. None of the authors were directly involved in the collection or physical analysis of semen samples. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

The emergence of conflicting reports on the natural occurrence of Alzheimer's disease (AD) in non-human primates has prompted research on the comparison of the role of diet-associated changes in gene expression between humans and non-human primates. This article analyzes the effects of different human and chimpanzee diets and their link with apolipoproteins, lipid, and iron (Fe) metabolism, starting from available data, to find out any gap in the existing knowledge. By using a system biology approach, we have re-analyzed the liver and brain RNA seq data of mice fed with either human or chimpanzee diet for 2 weeks to look for genetic differences that may explain the differences in AD occurrence between those two classes. In liver samples of mice fed with the chimpanzee diet in comparison to the human diet, apolipoprotein A-1, ceruloplasmin, and 10 other genes were upregulated while 21 genes were downregulated. However, brain apolipoprotein E4 gene expression was not changed upon diet. Genetic, structural, and functional differences in apolipoprotein E protein, along with differences in Fe metabolisms and a longer lifespan of humans during evolution may account for the observed disparity. [ABSTRACT FROM AUTHOR]

Staphylococcus spp. poses a significant threat to human and animal health due to their capacity to cause a wide range of infections in both. In this study, resistance genes conferring antibiotic resistance in Staphylococcus spp. and Mammaliicoccus sciuri isolates from humans and poultry in Edo state, Nigeria, were investigated. In April 2017, 61 Staphylococcus spp. isolates were obtained from urine, wounds, nasal and chicken fecal samples. Species identification was carried out by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Antimicrobial susceptibility testing was performed using the Kirby-Bauer method for 16 antibiotics. Whole-genome sequencing was used for characterization of the isolates. The 61 investigated isolates included Staphylococcus aureus, S. arlettae, M. sciuri, S. haemolyticus, and S. epidermidis. A total of 47 isolates (77%) belonged to human samples and 14 (23%) isolates were collected from poultry samples. All were phenotypically resistant to at least three antimicrobial(s). Multiple resistance determinants were detected in the human and poultry isolates analyzed. Phylogenetic analysis revealed close relatedness among the isolates within each species for S. arlettae, M. sciuri, and S. haemolyticus, respectively. This study delivered comprehensive genomic insights into antibiotic-resistant Staphylococcus species and M. sciuri isolates from human and poultry sources in Edo state, Nigeria, from a One Health perspective. [ABSTRACT FROM AUTHOR]

Objective: Our study examined the impact of sex, ADHD subtype, and comorbid illnesses (depression/anxiety) on the timing of diagnosis and treatment for ADHD. Method: To analyze ADHD patients, four health databases were used to assess subtype, comorbid mood, and antidepressant or anxiolytic drug exposure. Analyses were stratified by sex and age. Standardized mean differences measured intergroup differences. Results: Females with ADHD were identified at older ages and had higher rates of depression and anxiety diagnoses and treatments before and after their initial ADHD diagnosis. Predominantly inattentive ADHD patients were diagnosed later and more likely to receive mood disorder diagnosis and treatment than hyperactive impulsive ADHD patients. Conclusions: Results suggest a more complex ADHD presentation in females, potentially causing late diagnosis and delayed treatment. [ABSTRACT FROM AUTHOR]

The population from 25 villages in two municipalities on Rujan Mt. in southeastern Serbia (130 informants) was surveyed about human and ethnoveterinary medicine by completing a questionnaire containing general information about respondents and specific issues related to their applications. There were 2254 reports on the use of plants in human ethnopharmacology and 793 for ethnoveterinary medicine. The Informant Consensus Factor and comparison of ethnicity and gender for the most frequently reported plant taxa in human and ethnoveterinary medicine were calculated. Multivariate correspondence analysis was performed. A total of 101 medicinal plant taxa used in human ethnopharmacology and belonging to 42 families were recorded during the ethnobotanical research, of which 29 taxa are included in European Pharmacopoeia 10.2. The most frequently mentioned families were Asteraceae (502 reports) and Lamiaceae (404 reports). Hypericum perforatum L. (197 reports) and Matricaria chamomilla L. (164 reports) were the most used plant taxa. Among 17 categories, digestive (513 URs) and skin (331 URs) diseases were the most frequently reported. The research recorded 43 plant species used in ethnoveterinary medicine from 25 families. The most frequently mentioned families were Lamiaceae (6 reports) and Rosaceae (6 reports). The most used plant taxa were Fraxinus ornus L. (108 reports) and Helleborus odorus Waldst. & Kit. (80 reports). Among the six categories, the most reported diseases were digestive (267 reports), infectious (240 reports), and skin (159 reports). The present study contributes significantly to diversifying strategies in traditional human and ethnoveterinary medicine. [ABSTRACT FROM AUTHOR]

Many wildlife species vary habitat selection across space, time, and behavior to maximize rewards and minimize risk. Multi‐scale research approaches that identify variation in wildlife habitat selection can highlight not only habitat preferences and risk tolerance but also movement strategies that afford coexistence or cause conflict with humans. Here, we examined how anthropogenic and natural features influenced coyote (Canis latrans) habitat selection in a mixed‐use, agricultural landscape in Mendocino County, California, USA. We used resource selection functions and hidden Markov models to test whether coyote selection for anthropogenic and natural features varied by time of day or by behavioral state (resting, foraging, and traveling). We found that coyotes avoided development, but, contrary to our expectations, coyotes selected for roads, agriculture, and areas with risk of human encounter and rifle use regardless of diel period or behavioral state. While traveling, coyotes increased selection for roads and avoided ruggedness, indicating that unpaved roads may enhance connectivity for coyotes in mixed‐use landscapes. Finally, we found that coyotes selected for mountain lion habitat when resting and at night, signifying that risk from natural predators was not a factor in habitat selection at coarse scales. Coyote habitat selection for places and times associated with human activity, without variation across scales, signals a potential for conflict if coyotes are perceived by people as a nuisance. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusion Clinical Significance To evaluate the color‐match with extracted natural teeth of three single‐shade universal composites, a group‐shade universal composite, and a highly translucent‐shade conventional composite.Twenty extracted human teeth were divided into light‐ and dark‐shade groups (n = 10, LSG and DSG). A preparation was restored with the 3 single‐shade universal composites, OMNICHROMA (OMC), Admira Fusion x‐tra U (AFU), and Essentia U (ESU); a highly translucent‐shade conventional composite, Tetric EvoCeram T (TEC‐T); and two shades of a group‐shade universal composite—Filtek Universal Restorative (FUR A1 and A4). Composites were photopolymerized, polished, and stored in water for 24 h. The ΔE00 value between the unprepared and restored surfaces was obtained using a spectrophotometer. Composite placement and measurements were repeated three times per tooth. Color differences were statistically analyzed with the within‐between‐subjects t‐test and repeated‐measures analysis of variance (ANOVA), followed by post hoc pairwise comparisons with a Bonferroni adjustment (α = 0.05).There were no statistically significant differences between OMC and FUR (A1 and A4). AFU and ESU showed significantly higher ΔE00 values than OMC and TEC‐T (p < 0.05). Single‐shade composites exhibited significantly higher ΔE00 values in the DSG than in the LSG except ESU (p < 0.05). None of the composites satisfied the criteria for an acceptable match (ΔE00 >1.8).OMC showed the same color matching ability as a group‐shade universal composite. A highly translucent‐shade conventional composite and OMC exhibited better color matching ability than other single‐shade composites. Overall, single‐shade universal composites performed better in lighter‐shaded teeth.Single‐shade universal composites have the potential to reduce chair time by eliminating shade selection in cavities with lighter‐shade teeth. Highly translucent incisal conventional composites also may be used if the appropriate shade of composite is not available. [ABSTRACT FROM AUTHOR]

Background: In literature, the levels of miRNA-146a and miRNA-155 are increased in periodontitis. Limited data are available regarding the expression of miRNA-146a and miR-NA-155 in diseased human peri-implant tissue. Therefore, the objective of this study was to explore the expression of miRNA-146a and miRNA-155 in human gingival peri-implant tissue affected by peri-implantitis. Methods: After recording the clinical parameters, human peri-implant pocket tissues were harvested from sites diagnosed with peri-implantitis (n = 15 cases) in addition to healthy peri-implant sulcus tissues (n = 15 controls). The levels of miRNA-146a and miRNA-155 were assessed using real-time qPCR. Results: Cases exhibited a significantly higher mean expression of miRNA-155 (5.2-fold increase) and miRNA-146a (2.8-fold increase) than controls. MiRNA-155 and miRNA-146a demonstrated an appropriate sensitivity (87.5% and 87.5%, respectively) and specificity (73.3% and 66.7%, respectively) in discriminating cases from controls. A moderate correlation (r = 0.544, p = 0.029) was found between miRNA-155 and miRNA-146a levels in the case group. Conclusions: The expressions of miRNA-146a and miR-NA-155 are different between healthy and peri-implantitis affected tissues. Both miRNAs might potentially able to discriminate healthy from peri-implantitis affected tissues. [ABSTRACT FROM AUTHOR]

Colorectal cancer ranks second in cancer-related deaths throughout the world. At the time of diagnosis, at least 20% of the patients with CRC had already developed metastases. Treating and effectively managing metastatic colorectal cancer remains an unsolved task for the health sector. Research and clinical trials have been done to find the best possible solution for patients diagnosed with metastatic colorectal cancer. The approval of the combination therapy of trifluridine and tipiracil with bevacizumab for previously treated metastatic colorectal cancer (CRC) by the Food and Drug Administration (FDA) is a remarkable breakthrough in CRC treatment. Our goal through this article is to give detailed knowledge about the pathogenesis of CRC, its prevalence, and its clinical features. Here, we have also discussed the past medical treatments that have been used for treating mCRC, including the anti-EGFR therapy, aflibercept, ramucirumab, and regorafenib. However, the focus of this document is to assess the combination of LONSURF (trifluridine/tipiracil) and bevacizumab by reviewing the clinical trials and relevant research. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) affects many body functions and activities, including work capacity and ability to work. An evaluation of work-related parameters is important to understand the barriers to maintaining the job. The aim of this study was to evaluate if a Comprehensive International Classification of Functioning, Disability and Health (ICF) core set for MS can be used to predict work capacity and employment status. Methods: The cohort included 151 participants with MS (99 female/52 male, mean age 49 years) referred for a work capacity evaluation. Results: 71 (47.0%) were employed and a major part (131, 86.7%) had a work capacity between 20 and 40% with no difference between those who were employed and those who were unemployed. The analysis revealed that age and the following categories explained 68.8% of the work capacity: b770 Gait pattern functions; b730 Muscle power functions; b134 Sleep functions; d845 Acquiring, keeping and terminating a job; and b620 Urination functions. The following categories in 79.5% predicted ability to work: b164 Higher-level cognitive functions; d510 Washing oneself; d630; Preparing meals; and d870 Economic self-sufficiency. Conclusions: Here, we show that different functions/activities predicted work capacity in comparison with employment status in MS. Therefore, ICF should be implemented when assessing work ability. [ABSTRACT FROM AUTHOR]

Cannabinoid CB2 receptor agonists are in development as therapeutic agents, including for immune modulation and pain relief. Despite promising results in rodent preclinical studies, efficacy in human clinical trials has been marginal to date. Fundamental differences in ligand engagement and signalling responses between the human CB2 receptor and preclinical model species orthologues may contribute to mismatches in functional outcomes. This is a tangible possibility for the CB2 receptor in that there is a relatively large degree of primary amino acid sequence divergence between human and rodent. Here, we summarise CB2 receptor gene and protein structure, assess comparative molecular pharmacology between CB2 receptor orthologues, and review the current status of preclinical to clinical translation for drugs targeted at the CB2 receptor, focusing on comparisons between human, mouse and rat receptors. We hope that raising wider awareness of, and proposing strategies to address, this additional challenge in drug development will assist in ongoing efforts toward successful therapeutic translation of drugs targeted at the CB2 receptor. LINKED ARTICLES: This article is part of a themed issue Therapeutic Targeting of G Protein‐Coupled Receptors: hot topics from the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists 2021 Virtual Annual Scientific Meeting. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.14/issuetoc [ABSTRACT FROM AUTHOR]

Background: Exposure to poly- and perfluoroalkyl substances (PFAS) may affect infant and childhood health through immunosuppression. However, the findings of epidemiological literature examining relationships between prenatal/childhood PFAS exposure and vaccine response and infection in humans are still inconclusive. The aim of this review was to examine the effects of PFAS exposure on vaccine antibody response and infection in humans. Methods: The MEDLINE/Pubmed database was searched for publications until 1 February 2023 to identify human studies on PFAS exposure and human health. Eligible for inclusion studies had to have an epidemiological study design and must have performed logistic regression analyses of gestational or childhood exposure to PFAS against either antibody levels for pediatric vaccines or the occurrence of children's infectious diseases. Information on baseline exposure to PFAS (in ng/mL), the age of PFAS exposure (gestational or in years), and the outcome was measured, potentially leading to multiple exposure-outcome comparisons within each study was collected. Percentage change and standard errors of antibody titers and occurrence of infectious diseases per doubling of PFAS exposure were calculated, and a quality assessment of each study was performed. Results: Seventeen articles were identified matching the inclusion criteria and were included in the meta-analysis. In general, a small decrease in antibody response and some associations between PFAS exposure and childhood infections were observed. Conclusions: This meta-analysis summarizes the findings of PFAS effects on infant and childhood immune health. The immunosuppression findings for infections yielded suggestive evidence related to PFAS exposure, particularly PFOS, PFOA, PFHxS, and PFNA but moderate to no evidence regarding antibody titer reduction. Systematic review registration: The research protocol of this systematic review is registered and accessible at the Open Science Framework (https://doi.org/10.17605/OSF.IO/5M2VU). [ABSTRACT FROM AUTHOR]

Objective: Rare coexistence of disease or pathology Background: Leishmaniasis is a zoonosis with worldwide prevalence that causes dermal lesions and can be serious in humans. This report presents a case of cutaneous leishmaniasis (CL) that was apparently associated with a zoonotic transmission in a peri-urban area of the city of Portoviejo, Ecuador, close to mountainous and forested sites. Case Report: For 37 years, we have studied transmission of leishmaniasis in Ecuador, and have seen a wide variety of clinical presentations of the disease caused by different strains of the parasite Leishmania in patients, including pregnant women, without marked difference among them. CL without complications causes painless lesions of different clinical aspect. The present study reports a case of a 25-year-old woman presenting with severely inflamed, disseminated, and painful lesions of CL. The patient was not given antimonial treatment; however, local cryotherapy was given, together with topical anti-inflammatory and antibiotic ointment. All the lesions were observed to heal, and no amastigotes were found in smear stains after clinical healing. Since there was no reactivation after 1.5 years of follow-up, conventional antileishmanial treatment with meglumine antimoniate was not given to the patient. Conclusions: This report shows the importance of a properly done epidemiological and clinical presumtive diagnosis, followed by parasitological confirmation, and the benefit of using an alternative treatment for vulnerable patients, such as this pregnant woman, for whom the therapy with pentavalent antimonials is not indicated. All observed lesions healed and no amastigotes were found in the smears after clinical healing. [ABSTRACT FROM AUTHOR]

Sleep and brain/cognitive/neural reserve significantly impact well-being and cognition throughout life. This review aims to explore the intricate relationship between such factors, with reference to their effects on human cognitive functions. The specific goal is to understand the bidirectional influence that sleep and reserve exert on each other. Up to 6 February 2024, a methodical search of the literature was conducted using the PubMed database with terms related to brain, cognitive or neural reserve, and healthy or disturbed sleep. Based on the inclusion criteria, 11 articles were selected and analyzed for this review. The articles focus almost exclusively on cognitive reserve, with no explicit connection between sleep and brain or neural reserve. The results evidence sleep's role as a builder of cognitive reserve and cognitive reserve's role as a moderator in the effects of physiological and pathological sleep on cognitive functions. In conclusion, the findings of the present review support the notion that both sleep and cognitive reserve are critical factors in cognitive functioning. Deepening comprehension of the interactions between them is essential for devising strategies to enhance brain health and resilience against age- and pathology-related conditions. [ABSTRACT FROM AUTHOR]

Simple Summary: Animals and plants present asymmetric structures in nature. The most relevant motor behavioural manifestation of lateralisation is handedness, which is defined as the consistent use of one effector rather than the other in performing certain tasks. In animals, including human beings, handedness is associated with the presence of a nervous system. Researchers have recently challenged this idea by reporting that even organisms without a nervous system, such as plants, exhibit similarities with animals in terms of directional movement patterns (i.e., right-handed prevalence), opening up the possibility of a comparative study of handedness across taxa. Here, we advance a comparative approach to the study of handedness in plants by adopting the experimental paradigms already used to research laterality in various animal species. Structural and functional asymmetries are traceable in every form of life, and some lateralities are homologous. Functionally speaking, the division of labour between the two halves of the brain is a basic characteristic of the nervous system that arose even before the appearance of vertebrates. The most well-known expression of this specialisation in humans is hand dominance, also known as handedness. Even if hand/limb/paw dominance is far more commonly associated with the presence of a nervous system, it is also observed in its own form in aneural organisms, such as plants. To date, little is known regarding the possible functional significance of this dominance in plants, and many questions remain open (among them, whether it reflects a generalised behavioural asymmetry). Here, we propose a comparative approach to the study of handedness, including plants, by taking advantage of the experimental models and paradigms already used to study laterality in humans and various animal species. By taking this approach, we aim to enrich our knowledge of the concept of handedness across natural kingdoms. [ABSTRACT FROM AUTHOR]

Beside the well‐documented involvement of secondary somatosensory area, the cortical network underlying late somatosensory evoked potentials (P60/N60 and P100/N100) is still unknown. Electroencephalogram and magnetoencephalogram source imaging were performed to further investigate the origin of the brain cortical areas involved in late somatosensory evoked potentials, using sensory inputs of different strengths and by testing the correlation between cortical sources. Simultaneous high‐density electroencephalograms and magnetoencephalograms were performed in 19 participants, and electrical stimulation was applied to the median nerve (wrist level) at intensity between 1.5 and 9 times the perceptual threshold. Source imaging was undertaken to map the stimulus‐induced brain cortical activity according to each individual brain magnetic resonance imaging, during three windows of analysis covering early and late somatosensory evoked potentials. Results for P60/N60 and P100/N100 were compared with those for P20/N20 (early response). According to literature, maximal activity during P20/N20 was found in central sulcus contralateral to stimulation site. During P60/N60 and P100/N100, activity was observed in contralateral primary sensorimotor area, secondary somatosensory area (on both hemispheres) and premotor and multisensory associative cortices. Late responses exhibited similar characteristics but different from P20/N20, and no significant correlation was found between early and late generated activities. Specific clusters of cortical activities were activated with specific input/output relationships underlying early and late somatosensory evoked potentials. Cortical networks, partly common to and distinct from early somatosensory responses, contribute to late responses, all participating in the complex somatosensory brain processing. [ABSTRACT FROM AUTHOR]

Resting state functional magnetic resonance imaging (R‐fMRI) offers insight into how synchrony within and between brain networks is altered in disease states. Individual and disease‐related variability in intrinsic connectivity networks may influence our interpretation of R‐fMRI data. We used a personalized approach designed to account for individual variation in the spatial location of correlation maxima to evaluate R‐fMRI differences between Parkinson's disease (PD) patients who showed cognitive decline, those who remained cognitively stable and cognitively stable controls. We compared fMRI data from these participant groups, studied at baseline and 18 months later, using both network‐based statistics (NBS) and calculations of mean inter‐ and intra‐network connectivity within pre‐defined functional networks. The NBS analysis showed that PD participants who remained cognitively stable showed exclusively (at baseline) or predominantly (at follow‐up) increased intra‐network connectivity, whereas decliners showed exclusively reduced intra‐network and inter‐ (ventral attention and default mode) connectivity, in comparison with the control group. Evaluation of mean connectivity between all regions of interest (ROIs) within a priori networks showed that decliners had consistently reduced inter‐network connectivity for ventral attention, somatomotor, visual and striatal networks and reduced intra‐network connectivity for ventral attention network to striatum and cerebellum. These findings suggest that specific functional connectivity covariance patterns differentiate PD cognitive subtypes and may predict cognitive decline. Further, increased intra and inter‐network synchrony may support cognitive function in the face of PD‐related network disruptions. [ABSTRACT FROM AUTHOR]

Anti‐aging research has made significant strides in identifying treatments capable of extending lifespan across a range of organisms, from simple invertebrates to mammals. This review showcases the current state of anti‐aging interventions, highlighting the lifespan extensions observed in animal models through various treatments and the challenges encountered in translating these findings to humans. Despite promising results in lower organisms, the translation of anti‐aging treatments to human applications presents a considerable challenge. This discrepancy can be attributed to the increasing complexity of biological systems, species‐specific metabolic and genetic differences, and the redundancy of metabolic pathways linked to longevity. Our review focuses on analyzing these challenges, offering insights into the efficacy of anti‐aging mechanisms across species and identifying key barriers to their translation into human treatments. By synthesizing current knowledge and identifying gaps in translatability, this review aims to underscore the importance of advancing these therapies for human benefit. Bridging this gap is essential to assess the potential of such treatments in extending the human healthspan. [ABSTRACT FROM AUTHOR]

Background/Aims: It is a common belief that constipated patients have hard feces that contributes to the difficulties defecating. To the best of our knowledge, no studies had been published on controlled evacuation of simulated feces with different consistencies. Methods: Twelve normal subjects were recruited for studies with the simulated feces device "Fecobionics" of different consistency (silicone shore 0A-40A corresponding to Bristol stool form scale types 2-4). The subjects filled out questionnaires and had the balloon expulsion test and anorectal manometry done for reference. The Fecobionics probes were inserted in rectum in random order with +20 minutes between insertions. The bag was filled to urge-to-defecate and evacuations took place in privacy. Non-parametric statistics with median and quartiles are provided. Results: One subject was excluded due to technical issues, and another had abnormal anorectal manometry-balloon expulsion test. The 4 females/6 males subjects were aged 23 (range 20-48) years. Most differences were observed between the 0A and 10A probe (duration, maximum bag pressure, duration x maximum bag pressure, and relaxation of the front pressure and the bend angle during evacuation), eg, the duration was 9 (8-12) seconds at 0A and 18 (12-21) seconds at 10A (P < 0.05), and maximum bag pressure was 107 (96-116) cmH2O at 0A and 140 (117-162) cmH2O at 10A (P < 0.05). The bend angle before evacuation differed between the probes whereas only the 10A differed from 40A during defecation. The 10A was harder to evacuate than the 0A probe. Except for the bend angles, no further significant change was observed from 10A to 40A. Conclusion: Fecal consistency affects defecatory parameters. [ABSTRACT FROM AUTHOR]