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The temporal pattern of action potentials can convey rich information in a variety of sensory systems. We describe a new non-invasive technique that enables precise, reliable generation of action potential patterns in tactile peripheral afferent neurons by brief taps on the skin. Using this technique, we demonstrate sophisticated coding of temporal information in the somatosensory system, that shows that perceived vibration frequency is not encoded in peripheral afferents as was expected by either their firing rate or the underlying periodicity of the stimulus. Instead, a burst gap or silent gap between trains of action potentials conveys frequency information. This opens the possibility of new encoding strategies that could be deployed to convey sensory information using mechanical or electrical stimulation in neural prostheses and brain-machine interfaces, and may extend to senses beyond artificial encoding of aspects of touch. We argue that a focus on appropriate use of effective temporal coding offers more prospects for rapid improvement in the function of these interfaces than attempts to scale-up existing devices.

Social touch is important for interpersonal interaction. Gentle touch and slow brushing are typically perceived as pleasant, the degree of pleasantness is linked to the activity of the C-tactile (CT) fibers, a class of unmyelinated nerves in the skin. The inability to experience pleasure in general is called anhedonia, a common phenomenon in the chronic pain condition fibromyalgia. Here, we studied the perception and cortical processing of gentle touch in a well-characterized cohort of fibromyalgia. Patients and controls participated in functional brain imaging while receiving tactile stimuli (brushing) on the forearm. They were asked to provide ratings of pleasantness of the tactile stimulus and ongoing pain. We found high distress, pain catastrophizing, and insomnia, and a low perceived state of health in fibromyalgia. Further, patients rated both slow (CT-optimal) and fast (CT-suboptimal) brushing as less pleasant than healthy participants. While there was no difference in brain activity during touch, patients showed deactivation in the right posterior insula (contralateral to the stimulated arm) during pleasantness rating and activation during pain rating. The opposite pattern was observed in healthy participants. Voxel-based morphometry analysis revealed reduced grey matter density in patients, in the bilateral hippocampus and anterior insula. Our results suggest anhedonia to gentle touch in fibromyalgia with intact early-stage sensory processing but dysfunctional evaluative processing. These findings contribute to our understanding of the mechanisms underlying anhedonia in fibromyalgia.

We recently showed that C low-threshold mechanoreceptors (CLTMRs) contribute to touch-evoked pain (allodynia) during experimental muscle pain. Conversely, in absence of ongoing pain, the activation of CLTMRs has been shown to correlate with a diffuse sensation of pleasant touch. In this study, we evaluated (1) the primary afferent fibre types contributing to positive (pleasant) and negative (unpleasant) affective touch and (2) the effects of tactile stimuli on tonic muscle pain by varying affective attributes and frequency parameters. Psychophysical observations were made in 10 healthy participants. Two types of test stimuli were applied: stroking stimulus using velvet or sandpaper at speeds of 0.1, 1.0 and 10.0 cm/s; focal vibrotactile stimulus at low (20 Hz) or high (200 Hz) frequency. These stimuli were applied in the normal condition (i.e. no experimental pain) and following the induction of muscle pain by infusing hypertonic saline (5%) into the tibialis anterior muscle. These observations were repeated following the conduction block of myelinated fibres by compression of sciatic nerve. In absence of muscle pain, all participants reliably linked velvet-stroking to pleasantness and sandpaper-stroking to unpleasantness (no pain). Likewise, low-frequency vibration was linked to pleasantness and high-frequency vibration to unpleasantness. During muscle pain, the application of previously pleasant stimuli resulted in overall pain relief, whereas the application of previously unpleasant stimuli resulted in overall pain intensification. These effects were significant, reproducible and persisted following the blockade of myelinated fibres. Taken together, these findings suggest the role of low-threshold C fibres in affective and pain processing. Furthermore, these observations suggest that temporal coding need not be limited to discriminative aspects of tactile processing, but may contribute to affective attributes, which in turn predispose individual responses towards excitatory or inhibitory modulation of pain.

Purpose. Tube-related exposure is a known complication of glaucoma drainage device (GDD) surgery. Our objective is to report the early (approximately 1 year) tube exposure rate of implants covered with a keraSys (IOP Inc., Costa Mesa, CA, USA) tissue reinforcement graft. Patients and Methods. A retrospective, noncomparative, consecutive case series of 42 eyes with GDD implantation with keraSys patch grafts was performed. Main outcome measurements included patch-related complications: patch exposure, tube exposure, wound dehiscence, and patch migration. Results. Forty-two eyes were followed for an average of 15.24±10.44 months (range 1.0–32.3 months). Four (10%) eyes experienced patch-related complications: two with exposure 8 months postoperatively, one with exposure 13 months postoperatively, and one with exposure 4 weeks postoperatively. Conclusion. The effectiveness of the keraSys patch graft is limited by the higher than expected early exposure rate found in this case series. These results should be confirmed in other studies.

Purpose. To evaluate intraobserver and interobserver agreement in locating the scleral spur landmark (SSL) and anterior chamber angle measurements obtained using Fourier Domain Anterior Segment Optical Coherence Tomography (ASOCT) images. Methods. Two independent, masked observers (SR and AZC) identified SSLs on ASOCT images from 31 eyes with open and nonopen angles. A third independent reader, NPB, adjudicated SSL placement if identifications differed by more than 80 μm. Nine months later, SR reidentified SSLs. Intraobserver and interobserver agreement in SSL placement, trabecular-iris space area (TISA750), and angle opening distance (AOD750) were calculated. Results. In 84% of quadrants, SR’s SSL placements during 2 sessions were within 80 μm in both the X- and Y-axes, and in 77% of quadrants, SR and AZC were within 80 μm in both axes. In adjudicated images, 90% of all quadrants were within 80 μm, 88% in nonopen-angle eyes, and 92% in open-angle eyes. The intraobserver and interobserver correlation coefficients (with and without adjudication) were above 0.9 for TISA750 and AOD750 for all quadrants. Conclusions. Reproducible identification of the SSL from images obtained with FD-ASOCT is possible. The ability to identify the SSL allows reproducible measurement of the anterior chamber angle using TISA750 and AOD750.

Abstract The heat flow and physical properties package measured soil thermal conductivity at the landing site in the 0.03–0.37 m depth range. Six measurements spanning solar longitudes from 8.0° to 210.0° were made and atmospheric pressure at the site was simultaneously measured using InSight's Pressure Sensor. We find that soil thermal conductivity strongly correlates with atmospheric pressure. This trend is compatible with predictions of the pressure dependence of thermal conductivity for unconsolidated soils under martian atmospheric conditions, indicating that heat transport through the pore filling gas is a major contributor to the total heat transport. Therefore, any cementation or induration of the soil sampled by the experiments must be minimal and soil surrounding the mole at depths below the duricrust is likely unconsolidated. Thermal conductivity data presented here are the first direct evidence that the atmosphere interacts with the top most meter of material on Mars.

A field experiment was conducted at the nursery of ornamental plants, Faculty of Agriculture, Minia University during 2018/2019 and 2019/2020 seasons to study the effect of three planting dates (November 1st, November 15th and December1st) and three plant spacings (10, 15 and 20 cm) on growth, yield and chemical composition of quinoa plants to obtain the best agricultural transactions under the conditions of Central Egypt. The results showed significant effects of planting dates on all the studied traits, except for plant height, weight of 1000 seeds and protein% in both seasons, with the planting date of November 15th being the best date. The effect of plant spacing was significant for all studied characters, except for weight of 1000 seeds and protein % in the first season. Planting quinoa seeds at 15 cm. was superior to the other spacings in most cases. The interaction between planting dates and plant spacing between plants was insignificant except for number of panicles/plant and yield of seeds/plant (g) in both seasons and the weight of 1000 seed (g) and seed yield/fed (ton) in the second season. Therefore, it is recommended to cultivate the quinoa on November 15th at a distance of 15 cm apart under the conditions of Central Egypt because it gave the best values ​​for economic characteristics

Objective. To assess histological changes of colonic mucosa in patients with clinically different types of irritable bowel syndrome (IBS) before and after the treatment with tetracyclic antidepressant and selective serotonin reuptake inhibitor. Methods. Adult patients (over 18 years) with confirmed diagnosis of IBS were examined. Biopsy specimens were taken from colon during colonoscopy for the next histological examination. One expert gastrointestinal pathologist assessed all tissue samples. We patent semi quantitative assessment of the severity of cell infiltration of colonic mucosa, which could be assessed as inflammatory (neutrophils), immune (lymphocytes, plasma cells, macrophages), or allergic (eosinophils) response (0 to 3 degrees). All patients received treatment due to the clinical variant of IBS: 1) IBS-constipation – mirtazapinum 15 mg/night+lactulose 30ml/morning (+30ml/night if needed); 2) IBS-diarrhea – escitalopram 5mg/night+rifaximine 600mg/twice a day; 3) IBS-unspecified – mirtazapinum 15 mg/escitalopram 5mg/ night; 4) IBS-mixed – mirtazapinum 15 mg, lactulose 30ml/morning (+30ml/night if needed) / escitalopram 5mg/night+rifaximine 600mg/twice a day. Results. 107 patients were examined, 36 of them had constipation (I group), 35 – diarrhea (II group), 22- unspecified variant (III group) and 12 patients had mixed variant of IBS (IV group) due to Rome III criteria (2006). 1st degree of lymphocyte infiltration was detected in 100% IBS-constipation patients and in 58,3% IBS-mixed variant (p0.05). No cases of 2nd or 3rd degree of colonic mucosa infiltration were found. Conclusion. After the treatment with tetracyclic antidepressant and selective serotonin reuptake inhibitor we found that the degree of inflammation of colonic mucosa was reduced or disappeared, due to the zero degree of infiltration according to our patented classification.

Chemoprotection by dietary agents is a promising strategy for cancer prevention. The aim of the present study was to evaluate the combined effect of tomato and garlic against 7,12-dimethylbenz- [a]anthracene (DMBA)-induced genetic damage and oxidative stress in 12-14-week-old male Swiss albino mice. The animals were randomized into experimental and control groups and divided into eight groups of five animals each. Group 1 animals were injected intraperitoneally with 35 mg/kg body weight DMBA suspended in peanut oil as a single dose. Groups 2-4 animals received tomato (500 mg/kg body weight), garlic (125 mg/kg body weight) and a combination of tomato and garlic for 5 days by gavage, respectively, followed by DMBA 1.5 h after the final feeding. The doses of tomato and garlic correspond to the average human daily consumption. Animals in groups 5, 6 and 7 received tomato alone, garlic alone and tomato + garlic combination, respectively, for 5 days. Group 8 animals received the same volume of water and served as control. The incidence of bone marrow micronuclei and the extent of lipid peroxidation and the concentrations of antioxidants glutathione, glutathione peroxidase and glutathione-S-transferase were measured in the liver, 48 h after DMBA exposure. Increased frequency of micronuclei and enhanced lipid peroxidation accompanied by compromised antioxidant defenses were observed in DMBA-treated animals. Although pretreatment with tomato or garlic significantly reduced the frequency of DMBA-induced bone marrow micronuclei, the combination of tomato and garlic exhibited more profound effect in inhibiting DMBA-induced genotoxicity and oxidative stress. We suggest that a broad spectrum of antimutagenic and anticlastogenic effects can be achieved through an effective combination of functional foods such as tomato and garlic.

Background and Objective: Systemic lupus erythematosus (SLE) is fairly common immunologic disorder, more common in females. Renal involvement in the form of nephritis is frequent with proteinuria, haematuria and even renal failure in uncontrolled cases. The objective of the present study was to assess the frequency of biopsy proven class I-V Lupus Nephritis at Fatima Memorial Hospital Lahore, which is a tertiary care teaching hospital. Methods: A descriptive study was conducted in the Department of Pathology at Fatima Memorial Hospital Lahore from January to December 2015. Both male and female patients with clinical suspicion of lupus nephritis having serum ANA and Anti-ds DNA level investigations were included. The staining methods performed for light microscopy were Hematoxylin and Eosin (HandE) in order to study the morphology and determine the frequency of five classes of Lupus Nephritis. Results: Among 38 patients, 18.4% were males and 81.6% were females which makes the male to female ratio, 1:5. Mean age of the patients was 26.55 ± 8.13 years with age range of 14 – 49 years. When the patients were assessed on the basis of biopsy by HandE staining, out of 38 patients, n = 05 belonged to class III, n = 32 belonged to class IV and n = 1 belonged to class V. Conclusions: Maximum number of the patients i.e. 84.21% were in class IV, then 13.16% were in class III and only 2.63% were in class V lupus nephritis. [ABSTRACT FROM AUTHOR]

MacroH2A histone variants are shown to mark a subset of enhancers in both normal and cancer cells. In mice, macroH2A deficiency is shown to facilitate increased activity of transcription stem cell-associated transcription factors.

Abstract Background One of the main limitations of radiation therapy is the resistance of tumor cells. This study aimed at evaluating the relationship between the expression of epidermal growth factor receptor (EGFR) and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) and tumor radiosensitivity in patients with non-small cell lung cancer. Methods Medical case files, pathological results for EGFR and EML4-ALK, and computerized tomography scans of patients with NSCLC treated with thoracic radiation therapy were analyzed. Results The sample size was 101 patients with mean age 58.43 ± 9.89 years. Statistically significant differences were observed in the mean reduction of long tumor diameter during the early treatment phase in EGFR-positive versus EGFR-negative patients (p value = 0.04) and in short tumor diameter during the late treatment phase in EGFR-positive versus EGFR-negative patients (p value = 0.04). Conclusion Patients with overexpression of EGFR mutations are more radiosensitive during the early treatment phase, and EML4-ALK mutations were less radiosensitive regardless of phases.

IntroductionThe role of pain as a warning system necessitates a rapid transmission of information from the periphery for the execution of appropriate motor responses. The nociceptive withdrawal reflex (NWR) is a physiological response to protect the limb from a painful stimulus and is often considered an objective measure of spinal nociceptive excitability. The NWR is commonly defined by its latency in the presumed Aδ-fiber range consistent with the canonical view that “fast pain” is signaled by Aδ nociceptors. We recently demonstrated that human skin is equipped with ultrafast (Aβ range) nociceptors. Here, we investigated the short-latency component of the reflex and explored the relationship between reflex latency and pain perception.MethodsWe revisited our earlier work on NWR measurements in which, following convention, only reflex responses in the presumed Aδ range were considered. In our current analysis, we expanded the time window to search for shorter latency responses and compared those with pain ratings.ResultsIn both cohorts, we found an abundance of recordings with short-latency reflex responses. In nearly 90% of successful recordings, only single reflex responses (not dual) were seen which allowed us to compare pain ratings based on reflex latencies. We found that shorter latency reflexes were just as painful as those in the conventional latency range.ConclusionWe found a preponderance of short-latency painful reflex responses. Based on this finding, we suggest that short-latency responses must be considered in future studies. Whether these are signaled by the ultrafast nociceptors remains to be determined.

This study describes a novel and versatile method of incorporating graphene nano-platelets (GNP) into composite laminates to investigate its effect on mode I and mode II interlaminar fracture toughness (ILFT). Non-woven thermoplastic veil interleaves have been modified by spray deposition with a GNP dispersion to give either a continuous or strip-patterned distribution. The coated interleaves were used to modify the interlaminar region of carbon fibre reinforced polymer (CFRP) laminates. The fracture surfaces were characterised by scanning electron and optical microscopy.The continuous GNP distribution in mode I prevented the formation of carbon fibre bridging, resulting in similar initiation and propagation values. In mode II, the increased thickness of the interlaminar region, coupled with the uneven fracture surface showed the highest increase in the mode II ILFT for the continuous GNP distribution. The strip-patterned GNP distribution showed reduced carbon fibre bridging compared to the baseline CFRP and thermoplastic interleave laminates. This may be due to small scale fibre bridging between the deposited GNP-strips which also lead to peaks and troughs in the load-displacement response. In mode II, it is suggested that the deposited GNP-strips were sufficiently tough to re-direct the propagating crack from the modified interlaminar region to the adjacent ply.

The established view is that vibrotactile stimuli evoke two qualitatively distinctive cutaneous sensations, flutter (frequencies < 60 Hz) and vibratory hum (frequencies > 60 Hz), subserved by two distinct receptor types (Meissner’s and Pacinian corpuscle, respectively), which may engage different neural processing pathways or channels and fulfil quite different biological roles. In psychological and physiological literature, those two systems have been labelled as Pacinian and non-Pacinian channels. However, we present evidence that low-frequency spike trains in Pacinian afferents can readily induce a vibratory percept with the same low frequency attributes as sinusoidal stimuli of the same frequency, thus demonstrating a universal frequency decoding system. We achieved this using brief low-amplitude pulsatile mechanical stimuli to selectively activate Pacinian afferents. This indicates that spiking pattern, regardless of receptor type, determines vibrotactile frequency perception. This mechanism may underlie the constancy of vibrotactile frequency perception across different skin regions innervated by distinct afferent types.

Schistosomiasis, caused by trematodes of genus Schistosoma, is among the most seriously neglected tropical diseases. Although rapid surveillance of risk areas for Schistosoma transmission is vital to control schistosomiasis, the habitat and infection status of this parasite are difficult to assess. Environmental DNA (eDNA) analysis, involving the detection of extra-organismal DNA in water samples, facilitates cost-efficient and sensitive biomonitoring of aquatic environments and is a promising tool to identify Schistosoma habitat and infection risk areas. However, in tropical wetlands, highly turbid water causes filter clogging, thereby decreasing the filtration volume and increasing the risk of false negatives. Therefore, in this study, we aimed to conduct laboratory experiments and field surveys in Lake Victoria, Mbita, to determine the appropriate filter pore size for S. mansoni eDNA collection in terms of particle size and filtration volume. In the laboratory experiment, aquarium water was sequentially filtered using different pore size filters. Targeting >3 µm size fraction was found to be sufficient to capture S. mansoni eDNA particles, regardless of their life cycle stage (egg, miracidia, and cercaria). In the field surveys, GF/D (2.7 µm nominal pore size) filter yielded 2.5-times the filtration volume obtained with a smaller pore size filter and pre-filtration methods under the same time constraints. Moreover, a site-occupancy model was applied to the field detection results to estimate S. mansoni eDNA occurrence and detection probabilities and assess the number of water samples and PCR replicates necessary for efficient eDNA detection. Overall, this study reveals an effective method for S. mansoni eDNA detection in turbid water, facilitating the rapid and sensitive monitoring of its distribution and cost-effective identification of schistosomiasis transmission risk areas., Competing Interests: Declaration of competing interest Toshifumi Minamoto is an inventor of the patent for the use of benzalkonium chloride for eDNA preservaion., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Migrants may have elevated exposure to stressors, which can affect their physical and mental well-being. However, migrants often experience a healthy immigrant effect, the applicability of this phenomena to eating disorders is unknown. We aimed to synthesize the available literature and estimate a summary measure of prevalence odds ratio for eating disorders in migrant populations compared to local populations., Methods: A literature search was conducted using MEDLINE, Embase, PsycINFO, and Web of Science with keywords on migration and eating disorders. Inclusion criteria involved using a validated eating disorder scale and having a comparator group. Two independent reviewers performed study screening and data extraction. The NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies was used to assess risk of bias. Random-effects models of meta-analysis were applied to compare eating disorder prevalence between migrants and local populations., Results: There were 10 studies included in our review (meta-analysis = 6, narrative synthesis = 4). Studies provided prevalence estimates for: any eating disorder, binge eating disorder, anorexia nervosa, and bulimia nervosa. Among studies with a diagnostic instrument, the pooled prevalence odds ratio (POR) between migrants and local populations for any eating disorder was 0.45 (95%CI: 0.35-0.59). However, a subgroup analysis of eating disorder instruments among studies using risk assessment tools demonstrated inconsistent findings, with both increases and decreases in prevalence., Conclusion: Migrants were found to have a lower prevalence of eating disorders compared to local populations, supporting the healthy immigrant hypothesis. However, this effect differs between diagnostic and risk assessment tools., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

The nociceptive withdrawal reflex (NWR) is a protective limb withdrawal response triggered by painful stimuli, used to assess spinal nociceptive excitability. Conventionally, the NWR is understood as having two reflex responses: a short-latency Aβ-mediated response, considered tactile, and a longer-latency Aδ-mediated response, considered nociceptive. However, nociceptors with conduction velocities similar to Aβ tactile afferents have been identified in human skin. In this study, we investigated the effect of a preferential conduction block of Aβ fibers on pain perception and NWR signaling evoked by intradermal electrical stimulation in healthy participants. We recorded a total of 198 NWR responses in the intact condition, and no dual reflex responses occurred within our latency bandwidth (50-150 ms). The current required to elicit the NWR was higher than the perceptual pain threshold, indicating that NWR did not occur before pain was felt. In the block condition, when the Aβ-mediated tuning fork sensation was lost while Aδ-mediated nonpainful cooling was still detectable (albeit reduced), we observed that the reflex was abolished. Further, short-latency electrical pain intensity at pre-block thresholds was greatly reduced, with any residual pain sensation having a longer latency. Although electrical pain was unaffected at suprathreshold current, the reflex could not be evoked despite a two-fold increase in the pre-block current and a five-fold increase in the pre-block pulse duration. These observations lend support to the possible involvement of Aβ-fiber inputs in pain and reflex signaling., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Thorell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cranial retained surgical sponges, known as "gossypiboma" or "textiloma", represent a rare but potentially severe complication following surgical procedures. While it is infrequent, it poses a significant risk, particularly in delicate surgical settings such as neurosurgery. The inadvertent retention of cotton balls or surgical gauzes may cause localized inflammation, infection, abscess, or neurologic sequelae. In the realm of neurosurgery, where precision is paramount, the occurrence of postoperative brain gossypibomas is particularly concerning. This case report contributes to the radiological literature by presenting a distinctive instance of postoperative brain gossypiboma. By delving into the radiological intricacies and potential contributing factors to the retention of surgical materials in neurosurgical procedures, our aim is to underscore the significance of a collaborative approach between neurosurgeons and radiologists for enhanced detection and prevention of such complication., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Background: Community and individual participation are crucial for the success of schistosomiasis control. The World Health Organization (WHO) has highlighted the importance of enhanced sanitation, health education, and Mass Drug Administration (MDA) in the fight against schistosomiasis. These approaches rely on the knowledge and practices of the community to be successful; however, where the community knowledge is low and inappropriate, it hinders intervention efforts. Hence, it is essential to identify barriers and misconceptions related to awareness of schistosomiasis, sources of infection, mode of transmission, symptoms, and control measures., Methods: This was a mixed-method cross-sectional study involving 1200 pre-school children randomly selected and examined for Schistosoma mansoni infection using the Kato-Katz technique. All parents/guardians of selected children were enrolled for a pre-tested questionnaire survey, while 42 were engaged in focus group discussions (FGDs). The level of knowledge and awareness among parents/guardians about schistosomiasis was evaluated in relation to the infection status of their pre-school children., Results: Among pre-school children, the prevalence of intestinal schistosomiasis was 45.1% (95% CI 41.7-48.5). A majority of parents/guardians (85.5%) had heard about schistosomiasis, and this awareness was associated with the participant's level of education (OR = 0.16, 95% CI 0.08, 0.34). In addition, a positive association was observed between higher educational attainment and knowledge of the causative agent (OR = 0.69, 95% CI 0.49, 0.96). Low education level was significantly associated with limited knowledge of transmission through lake water contact (OR = 0.71, 95% CI 0.52, 0.97) and infection from the lake (OR = 0.33, 95% CI 0.19, 0.57). Notably, parents/guardians who have heard of schistosomiasis could not recognize symptoms of S. mansoni infection, such as abdominal pain (91.8%, 815/888) and blood in the stool (85.1%, 756/888). Surprisingly, 49.8% (442/888) incorrectly identified hematuria (blood in urine), a key sign of S. haematobium, but not S. mansoni, in an endemic area for S. mansoni infection. The majority (82.6%, 734/888) of parents/guardians were unaware that dams are potential infection sites, despite 53.9% (479/888) of their pre-school-aged children testing positive for schistosome infection., Conclusions: Despite the high level of awareness of intestinal schistosomiasis in the study area, we identified a low level of knowledge regarding its causes, modes of transmission, signs and symptoms and potential sites of transmission within the community. This study emphasizes the need for targeted educational interventions to address the misconceptions and knowledge gaps surrounding intestinal schistosomiasis through tailored community-based programs., (© 2024. The Author(s).)

Objective: 177 Lu-PSMA-617-radioligand therapy (RLT) has shown promising therapeutic role in patients with metastatic castration-resistant prostate cancer. However, off-target action in salivary glands often presents with xerostomia. Personalized dosimetry can help in optimizing the treatment, however, has so far been tedious due to multiple time-point imaging. In this prospective study, we intended to estimate the absorbed dose delivered to the salivary glands in patients undergoing 177 Lu-PSMA-617-RLT using quantitative SPECT/CT at a single time point., Methods: Patients undergoing 177 Lu-PSMA-617 RLT were included in this prospective study. Post-therapy whole-body images and regional quantitative single time-point SPECT/CT were acquired at 24 h with high-energy collimator. The data was processed and analyzed using Q.Metrix software. A scaling factor, that is, the time-integrated activity conversion factor was applied for the image acquired at 24 h. Absorbed doses were computed using MIRD scheme and OLINDA software., Results: A total of 21 patients (mean age: 66 ± 9 years) were included. The value of mean absorbed dose for the parotid glands was 1.90 ± 1.31Gy (range: 0.26-6.23) and that for the submandibular glands was 1.37 ± 0.94Gy (range: 0.16-3.65). The mean absorbed doses per administered activity for the parotid and submandibular glands were 0.26 ± 0.18 Gy/GBq and 0.19 ± 0.12 Gy/GBq, respectively. The absorbed doses were estimated for one cycle of therapy and were well within acceptable limits. None of the patients experienced dryness of mouth., Conclusion: Single time-point dosimetry with quantitative SPECT/CT is feasible and can be standardized to estimate the absorbed dose to salivary glands instead of multiple time-point acquisitions., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Healthy eating habits are essential for improving nutritional status and strengthening immunity against infectious diseases. This study examined the relationship between diet quality and stunting in school-aged children in an infectious disease-endemic area of western Kenya., Methods: This cross-sectional study included 260 school-aged children (age 9-17 years) enrolled in primary schools in Mbita Sub-county, western Kenya. The nutritional status was assessed using anthropometric measurements. Dietary intake was measured using food frequency questionnaires and evaluated using the Food Pyramid (FP) score, which indicates adherence to the Kenyan food-based dietary guideline. Information on the children's age, sex, maternal education, and household wealth index was collected using a household-based questionnaire. Infections with the predominant parasites, such as Schistosoma (S.) mansoni, were detected via microscopy. The trend associations of the FP score with food group intake were examined to characterize the dietary intake of this population. Logistic regression analysis was performed to investigate the relationship between stunting and FP score tertiles, adjusted for sociodemographic and economic indicators and parasitic infection status., Results: Among the studied schoolchildren, 15.0% exhibited stunting, while 76.2% were infected with S. mansoni. The mean FP score was 25.6 out of 50 points. A higher FP score was characterized by a high intake of roots and tubers, dairy products, pulses, and fruits and a low intake of cereals and animal-source foods. The analysis revealed a trend: a lower risk of stunting was evident in groups with elevated FP scores (p for trend = 0.065). However, these trend associations were observable among subjects with either negative or light S. mansoni infection (p for trend = 0.016)., Conclusions: A higher quality diet, as evaluated by FP scores, was associated with a low risk of stunting among school-aged children. Notably, this association seemed to weaken in the presence of a high burden of S. mansoni infection. It highlights the importance of enhancing dietary quality through the promotion of diverse nutrient-dense foods alongside effective S. mansoni infection control for improved growth. This study contributes fundamental knowledge for understanding the diet-malnutrition relationship in areas endemic for S. mansoni infection., (© 2024. The Author(s).)

Little attention has been paid to neglected tropical diseases (NTDs) in high-income countries and no literature provides an overview of NTDs in Japan. This scoping review aims to synthesize the latest evidence and information to understand epidemiology of and public health response to NTDs in Japan. Using three academic databases, we retrieved articles that mentioned NTDs in Japan, written in English or Japanese, and published between 2010 and 2020. Websites of key public health institutions and medical societies were also explored. From these sources of information, we extracted data that were relevant to answering our research questions. Our findings revealed the transmission of alveolar echinococcosis, Buruli ulcer, Chagas disease, dengue, foodborne trematodiases, mycetoma, scabies, and soil-transmitted helminthiasis as well as occurrence of snakebites within Japan. Other NTDs, such as chikungunya, cystic echinococcosis, cysticercosis, leishmaniasis, leprosy, lymphatic filariasis, rabies, and schistosomiasis, have been imported into the country. Government agencies tend to organize surveillance and control programs only for the NTDs targeted by the Infectious Disease Control Law, namely, echinococcosis, rabies, dengue, and chikungunya. At least one laboratory offers diagnostic testing for each NTD except for dracunculiasis, human African trypanosomiasis, onchocerciasis, and yaws. No medicine is approved for treatment of Chagas disease and fascioliasis and only off-label use drugs are available for cysticercosis, opisthorchiasis, human African trypanosomiasis, onchocerciasis, schistosomiasis, and yaws. Based on these findings, we developed disease-specific recommendations. In addition, three policy issues are discussed, such as lack of legal frameworks to organize responses to some NTDs, overreliance on researchers to procure some NTD products, and unaffordability of unapproved NTD medicines. Japan should recognize the presence of NTDs within the country and need to address them as a national effort. The implications of our findings extend beyond Japan, emphasizing the need to study, recognize, and address NTDs even in high-income countries., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Harada et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Abstract: Androgen deprivation therapy plays an integral role in the treatment algorithm of advanced prostate cancer. Enzalutamide has shown great benefit in castrate-sensitive as well as resistant prostate cancer. Few studies have shown that enzalutamide can potentially increase the PSMA expression on 68 Ga-PSMA-11 PET/CT imaging in patients with metastatic castrate-resistant prostate cancer. We present an interesting case where addition of short course of enzalutamide resulted in increased localization of 177 Lu-PSMA-617 in metastatic lesions on posttherapy scan pointing to the added benefit of PSMA RLT., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Network meta-analysis (NMA) is increasingly used in guideline development and other aspects of evidence-based decision-making. We aimed to develop a risk of bias (RoB) tool to assess NMAs (RoB NMA tool). An international steering committee recommended that the RoB NMA tool to be used in combination with the Risk of Bias in Systematic reviews (ROBIS) tool (i.e. because it was designed to assess biases only) or other similar quality appraisal tools (eg, A MeaSurement Tool to Assess systematic Reviews 2 [AMSTAR 2]) to assess quality of systematic reviews. The RoB NMA tool will assess NMA biases and limitations regarding how the analysis was planned, data were analysed and results were presented, including the way in which the evidence was assembled and interpreted., Objectives: Conduct (a) a Delphi process to determine expert opinion on an item's inclusion and (b) a knowledge user survey to widen its impact., Design: Cross-sectional survey and Delphi process., Methods: Delphi panellists were asked to rate whether items should be included. All agreed-upon item were included in a second round of the survey (defined as 70% agreement). We surveyed knowledge users' views and preferences about the importance, utility and willingness to use the RoB NMA tool to evaluate evidence in practice and in policymaking. We included 12 closed and 10 open-ended questions, and we followed a knowledge translation plan to disseminate the survey through social media and professional networks., Results: 22 items were entered into a Delphi survey of which 28 respondents completed round 1, and 22 completed round 2. Seven items did not reach consensus in round 2. A total of 298 knowledge users participated in the survey (14% respondent rate). 75% indicated that their organisation produced NMAs, and 78% showed high interest in the tool, especially if they had received adequate training (84%). Most knowledge users and Delphi panellists preferred a tool to assess both bias in individual NMA results and authors' conclusions. Response bias in our sample is a major limitation as knowledge users working in high-income countries were more represented. One of the limitations of the Delphi process is that it depends on the purposive selection of experts and their availability, thus limiting the variability in perspectives and scientific disciplines., Conclusions: This Delphi process and knowledge user survey informs the development of the RoB NMA tool., Competing Interests: Competing interests: AAV was an Associate Editor for the journal, but was not involved with the decision or peer-review process., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Downsizing due to COVID-19 (COV-DS) and its consequences on laid-off employees has attracted the attention of many researchers, around the globe. However, the underlying mechanisms that explain the effects of COVID-19 downsizing (COV-DS) on the employees who have survived cutoffs remain underexplored. Grounded in the conservation of resources theory, this manuscript aims to study the causal path through which COV-DS reduces the survivors' affective commitment. The current study proposes the mediation of survivors' job uncertainty, stress, and organizational identification between COV-DS and survivors' affective commitment. This study also posits the moderating role of transformational leadership between COV-DS and both the mediators. The extant study has employed WARPED partial least square WARP PLS 7 and Hayes Process Macro to test the hypothesized relationships. Using the sample of 274 employees from the private sector of Pakistan, it was found that job uncertainty's stress strongly mediates the relationship between COV-DS and survivors' affective commitment. While mediation of survivors' organizational identification was not proven to be significant. However, with the moderation of transformational leadership, both the mediators were proven to be significant., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Samreen, Nagi, Naseem and Gul.)

Atypical teratoid/rhabdoid tumor (AT/RT) represents a rare malignant embryonic tumor of infant and early childhood. Its prognosis remains dismal despite aggressive multimodal treatment. We report the case of a 24-year-old male who was diagnosed with left parietal AT/RT after total resection and who is still in good health and recurrence free 4 years after surgery and adjuvant chemotherapy and radiotherapy., Competing Interests: None

Background and Purpose: Multinodular and vacuolating neuronal tumor (MVNT) of the cerebrum is a rare brain lesion with suggestive imaging features. The aim of our study was to report the largest series of MVNTs so far and to evaluate the utility of advanced multiparametric magnetic resonance (MR) techniques., Methods: This multicenter retrospective study was approved by our institutional research ethics board. From July 2014 to May 2019, two radiologists read in consensus the MR examinations of patients presenting with a lesion suggestive of an MVNT. They analyzed the lesions' MR characteristics on structural images and advanced multiparametric MR imaging., Results: A total of 64 patients (29 women and 35 men, mean age 44.2 ± 15.1 years) from 25 centers were included. Lesions were all hyperintense on fluid-attenuated inversion recovery and T2-weighted imaging without post-contrast enhancement. The median relative apparent diffusion coefficient on diffusion-weighted imaging was 1.13 [interquartile range (IQR), 0.2]. Perfusion-weighted imaging showed no increase in perfusion, with a relative cerebral blood volume of 1.02 (IQR, 0.05) and a relative cerebral blood flow of 1.01 (IQR, 0.08). MR spectroscopy showed no abnormal peaks. Median follow-up was 2 (IQR, 1.2) years, without any changes in size., Conclusions: A comprehensive characterization protocol including advanced multiparametric magnetic resonance imaging sequences showed no imaging patterns suggestive of malignancy in MVNTs. It might be useful to better characterize MVNTs., (© 2020 European Academy of Neurology.)

Pituitary apoplexy is an uncommon but potentially life-threatening emergency due to abrupt ischemic infarction or hemorrhage of the pituitary tumor. In many instances, pituitary apoplexy is the initial presentation in patients who were not previously diagnosed to have pituitary adenomas. Variety of precipitating factors have been linked to the occurrence of pituitary apoplexy, which include pregnancy. However, pituitary apoplexy related to pregnancy is limited to isolated case reports and very small case series. The main symptom is headache of sudden onset associated with visual disturbances, signs of meningeal irritation, and/or endocrine dysfunction. In the context of pregnancy the diagnosis of pituitary apoplexy can be challenging and confused with other complex conditions such as pre-eclampsia. Magnetic resonance imaging is the most sensitive sequence to confirm the diagnosis by revealing a pituitary tumor with hemorrhagic and/or necrotic components. Corticotropic deficiency with adrenal insufficiency is a potentially life-threatening disorder for both mother and the fetus if left untreated. The choice between conservative management with dopamine agonists and glucocorticoid, this "wait and see approach" and trans-sphenoidal resection depend on the severity of neuro-ophtalmic signs and the gestational week. In this article, we present three cases of pituitary apoplexy related to pregnancy. Pituitary apoplexy occurred in the third trimester in the three cases. It was the first presentation of an unknown pituitary adenoma in two cases, and complicated a preexisting macroprolactinoma in the other case. All three cases of our patients had sudden onset of severe headache and deterioration of the visual field in two cases. The pituitary MRI performed in our patients was the essential tool confirming the diagnosis of pituitary apoplexy. In all the patients was prompt replacement of deficient hormones especially glucocorticoids with close surveillance. The trans-sphenoidal resection was indicated in two pregnant women; as the first choice treatment in one case presenting with papillary edema, and as the second line after the deterioration of the visual field in one case. In the lack of guidelines of management pituitary apoplexy in case of pregnancy, we review the existing literature with pertinent clinical presentation, radiological findings, management and maternal/fetal outcomes of this rare pathology. The aim is to provide a rational framework for therapeutic management of pituitary apoplexy during pregnancy., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Multinodular and vacuolating neuronal tumor of the cerebrum is a rare supratentorial brain tumor described for the first time in 2013. Here, we report 11 cases of infratentorial lesions showing similar striking imaging features consisting of a cluster of low T1-weighted imaging and high T2-FLAIR signal intensity nodules, which we referred to as multinodular and vacuolating posterior fossa lesions of unknown significance. No relationship was found between the location of the lesion and clinical symptoms. A T2-FLAIR hypointense central dot sign was present in images of 9/11 (82%) patients. Cortical involvement was present in 2/11 (18%) of patients. Only 1 nodule of 1 multinodular and vacuolating posterior fossa lesion of unknown significance showed enhancement on postcontrast T1WI. DWI, SWI, MRS, and PWI showed no malignant pattern. Lesions did not change in size or signal during a median follow-up of 3 years, suggesting that multinodular and vacuolating posterior fossa lesions of unknown significance are benign malformative lesions that do not require surgical intervention or removal., (© 2019 by American Journal of Neuroradiology.)

In Kenya, communities residing along the shores and islands of Lake Victoria bear a substantial burden of schistosomiasis. Although there is a school-based deworming program in place, the transmission of Schistosoma mansoni varies even at a fine scale. Given the focal nature of schistosomes' transmission, we aim to identify areas with high intensity of S. mansoni infection in Mbita, Homabay County, western Kenya, for prioritized integrated control measures. Our findings confirm a high intensity of S. mansoni infection cluster around Mbita causeway. While the current efforts to curtail morbidity due to schistosomiasis through preventive chemotherapy in schools are crucial, fine-scale mapping of risk areas is necessary for specific integrated control measures., Competing Interests: The ethical review unit of KEMRI reviewed and approved this study (SERU No. 3092), and ethical review board of Institute of Tropical Medicine, Nagasaki University, Japan (No. 10121666). All parents/guardians gave a written consent while the preschool children ascended to the study.Publication for this report was authorized by the director KEMRI.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Pituitary tuberculosis is very rare. Its diagnosis is difficult unless a bacteriological or histological evidence of tuberculosis., Observation: We report the case of a 54 years old woman who presented with a pituitary coma that occurred two weeks after the initiation of antituberculous therapy for cervical lymph node tuberculosis. Resonance magnetic imaging showed a pseudotumoral aspect of the pituitary gland. She had hormonal replacement and anti-tuberculous therapy. Outcome was favourable with the normalization of both the pituitary function and the pituitary volume. However, an acute hypopituitarism happened eight months after the withdrawal of antituberculous, which were taken during 12 months. The re initiation of anti tuberculous therapy and its extension to two years leaded to a prolonged remission., Conclusion: the three-phase outcome confirms the tuberculous origin of the hypophysitis in our patient.

Immune responses to parasitic pathogens are affected by the host physiological condition. High-density lipoprotein (HDL) and low-density lipoprotein (LDL) are transporters of lipids between the liver and peripheral tissues, and modulate pro-inflammatory immune responses. Pathogenic mycobacteria are parasitic intracellular bacteria that can survive within macrophages for a long period. Macrophage function is thus key for host defense against mycobacteria. These basic facts suggest possible effects of HDL and LDL on mycobacterial diseases, which have not been elucidated so far. In this study, we found that HDL and not LDL enhanced mycobacterial infections in human macrophages. Nevertheless, we observed that HDL remarkably suppressed production of tumor necrosis factor alpha (TNF-α) upon mycobacterial infections. TNF-α is a critical host-protective cytokine against mycobacterial diseases. We proved that toll-like receptor (TLR)-2 is responsible for TNF-α production by human macrophages infected with mycobacteria. Subsequent analysis showed that HDL downregulates TLR2 expression and suppresses its intracellular signaling pathways. This report demonstrates for the first time the substantial action of HDL in mycobacterial infections to human macrophages.

Thioredoxin 1 (Trx1) and glutaredoxin 1 (Grx1) are two ubiquitous redox enzymes that are central for redox homeostasis but also are implicated in many other processes, including stress sensing, inflammation, and apoptosis. In addition to their enzymatic redox activity, a growing body of evidence shows that Trx1 and Grx1 play regulatory roles via protein-protein interactions with specific proteins, including Ask1. The currently available inhibitors of Trx1 and Grx1 are thiol-reactive electrophiles or disulfides that may suffer from low selectivity because of their thiol reactivity. In this report, we used a phage peptide library to identify a 7-mer peptide, 2GTP1, that binds to both Trx1 and Grx1. We further showed that a cell-permeable derivative of 2GTP1, TAT-2GTP1, disrupts the Trx1-Ask1 interaction, which induces Ask1 phosphorylation with subsequent activation of JNK, stabilization of p53, and reduced viability of cancer cells. Notably, as opposed to a disulfide-derived Trx1 inhibitor (PX-12), TAT-2GTP1 was selective for activating the Ask1 pathway without affecting other stress signaling pathways, such as endoplasmic reticulum stress and AMPK activation. Overall, 2GTP1 will serve as a useful probe for investigating protein interactions of Trx1.

Background: Large-scale schistosomiasis control programs are implemented in regions with diverse social and economic environments. A key epidemiological feature of schistosomiasis is its small-scale heterogeneity. Locally profiling disease dynamics including risk factors associated with its transmission is essential for designing appropriate control programs. To determine spatial distribution of schistosomiasis and its drivers, we examined schoolchildren in Kwale, Kenya., Methodology/principal Findings: We conducted a cross-sectional study of 368 schoolchildren from six primary schools. Soil-transmitted helminths and Schistosoma mansoni eggs in stool were evaluated by the Kato-Katz method. We measured the intensity of Schistosoma haematobium infection by urine filtration. The geometrical mean intensity of S. haematobium was 3.1 eggs/10 ml urine (school range, 1.4-9.2). The hookworm geometric mean intensity was 3.2 eggs/g feces (school range, 0-17.4). Heterogeneity in the intensity of S. haematobium and hookworm infections was evident in the study area. To identify factors associated with the intensity of helminth infections, we utilized negative binomial generalized linear mixed models. The intensity of S. haematobium infection was associated with religion and socioeconomic status (SES), while that of hookworm infection was related to SES, sex, distance to river and history of anthelmintic treatment., Conclusions/significance: Both S. haematobium and hookworm infections showed micro-geographical heterogeneities in this Kwale community. To confirm and explain our observation of high S. haematobium risk among Muslims, further extensive investigations are necessary. The observed small scale clustering of the S. haematobium and hookworm infections might imply less uniform strategies even at finer scale for efficient utilization of limited resources.

The expression levels of cyclooxygenase (COX)-2 and the prostaglandin E2 (PGE2) content have been associated with poor prognosis in patients with colorectal cancer (CRC). There is a strong correlation between COX-2 expression and PGE2 production in tissues from CRC patients, suggesting an important role for COX-2 on the regulation of PGE2 production. Previous studies by the present authors, where CRC patients were divided into high- or low-COX-2 expressing tumors, displayed important differences in the expression levels of several transcription factors involved in carcinogenesis. Among them, FBJ murine osteosarcoma viral oncogene homolog B (FosB), which is a member of the activator protein-1 complex, was the highest upregulated transcription factor in patients with high expression levels of COX-2. The present study aimed to investigate the role of FosB on the COX-2/PGE2 axis in CRC cells with high COX-2 expression levels. Interference RNA technology was used to knockdown FosB expression in HCA-7 cells, and 72 h later the messenger (m)RNA expression levels of COX-1 and COX-2, as well as the PGE2 content, were measured. The results indicated that FosB knockdown decreased the expression levels of COX-2 but did not affect the PGE2 content or the mRNA expression levels of COX-1. The present findings suggest an important role for FosB on the regulation of COX-2 expression, but no effect on the regulation of the PGE2 levels. In addition, the present results imply independent regulatory mechanisms for COX-2 expression and PGE2 content.