The anti-inflammatory properties of green tea extract protect against gentamicin-induced kidney injury.

We assessed in vivo the protective effects and underlying antioxidant and anti-inflammatory properties of dry green tee extract (GTE) on glomerular and tubular kidney function and structure in an experimental model of gentamicin (GEN)-induced nephrotoxicity. Wistar rats were divided into four groups and treated daily for 10 days. The control group received distilled water; the GTE group received 20 µg/g body weight (BW) GTE by gavage; the GEN group received 100 mg/g BW GEN intraperitoneally; and the GEN+GTE group received GTE and GEN simultaneously, as described above. At the beginning and end of treatment, the serum creatinine, fractional excretion of sodium and potassium, and plasma heme oxygenase (HO)-1 levels and oxidative stress (OS) were assessed. At the end of the experiment, kidney fragments were collected for histological evaluation and immunohistochemical studies of cyclooxygenase (COX)-2 and nuclear factor (NF)kB. The levels of interleukin (IL)-1b, IL-4, IL-6, IL-10 and monocyte chemotactic protein (MCP)-1 were measured in kidney tissue. The results showed that GTE attenuated significantly kidney structural injury and prevented GEN-induced kidney functional injury (glomerular and tubular function). GTE significantly attenuated the kidney tissue increase of the proinflammatory mediators NF-kB, COX2, IL-1b and MCP-1 and significantly increased the kidney expression of the anti-inflammatory cytokines IL-6 and IL-10. However, GTE did not prevent OS increase in GEN-treated animals. In conclusion, GTE protected against GEN nephrotoxicity, likely due to direct blockade of the inflammatory cascade, which might had occurred independently of its antioxidant effect.

Mobilization of isotopically heavy sulfur during serpentinite subduction.

Primitive arc magmas are more oxidized and enriched in sulfur-34 (34S) compared to mid-ocean ridge basalts. These findings have been linked to the addition of slab-derived volatiles, particularly sulfate, to arc magmas. However, the oxidation state of sulfur in slab fluids and the mechanisms of sulfur transfer in the slab remain inconclusive. Juxtaposed serpentinite and eclogitic metagabbro from the Voltri Massif (Italy) provide evidence for sulfur mobilization and associated redox processes during infiltration of fluids. Using bulk rock and in situ δ34S measurements, combined with thermodynamic calculations, we document the transfer of bisulfide-dominated, 34S-enriched fluids in equilibrium with serpentinite into adjacent metagabbro. We argue that the process documented in this study is pervasive along the subduction interface and infer that subsequent melting of these reacted slab-mantle interface rocks could produce melts that display the characteristic oxygen fugacity and sulfur isotope signatures of arc magmas worldwide.

Outcomes and Mechanisms Associated With Selective Thalamic Neuronal Loss in Chronic Traumatic Brain Injury.

Importance: The chronic neuronal burden of traumatic brain injury (TBI) is not fully characterized by routine imaging, limiting understanding of the role of neuronal substrates in adverse outcomes. Objective: To determine whether tissues that appear healthy on routine imaging can be investigated for selective neuronal loss using [11C]flumazenil (FMZ) positron emission tomography (PET) and to examine whether this neuronal loss is associated with long-term outcomes. Design, Setting, and Participants: In this cross-sectional study, data were collected prospectively from 2 centers (University of Cambridge in the UK and Weill Cornell Medicine in the US) between September 1, 2004, and May 31, 2021. Patients with TBI (>6 months postinjury) were compared with healthy control participants (all aged >18 years). Individuals with neurological disease, benzodiazepine use, or contraindication to magnetic resonance imaging were excluded. Data were retrospectively collated with nonconsecutive recruitment, owing to convenience and scanner or PET ligand availability. Data were analyzed between February 1 and September 30, 2023. Exposure: Flumazenil voxelwise binding potential relative to nondisplaceable binding potential (BPND). Main Outcomes and Measures: Selective neuronal loss identified with FMZ PET was compared between groups on voxelwise and regional scales, and its association with functional, cognitive, and psychological outcomes was examined using Glasgow Outcome Scale (GOS) scores, measures of sustained executive attention (animal and sustained fluency), and 36-Item Short Form Health Survey (SF-36) scores. Diffusion tensor imaging was used to assess structural connectivity of regions of cortical damage, and its association with thalamic selective neuronal loss. Results: In this study, 24 patients with chronic TBI (mean [SD] age, 39.2 [12.3] years; 18 men [75.0%]) and 33 healthy control participants (mean [SD] age, 47.6 [20.5] years; 23 men [69.7%]) underwent FMZ PET. Patients with TBI had a median time of 29 (range, 7-95) months from injury to scan. They displayed selective neuronal loss in thalamic nuclei, over and above gross volume loss in the left thalamus, and bilateral central, mediodorsal, ventral-lateral dorsal, anterior, and ventral anterior thalamic nuclei, across a wide range of injury severities. Neuronal loss was associated with worse functional outcome using GOS scores (left thalamus, left ventral anterior, and bilateral central, mediodorsal, and anterior nuclei), worse cognitive outcome on measures of sustained executive attention (left thalamus, bilateral central, and right mediodorsal nuclei), and worse emotional outcome using SF-36 scores (right central thalamic nucleus). Chronic thalamic neuronal loss partially mirrored the location of primary cortical contusions, which may indicate secondary injury mechanisms of transneuronal degeneration. Conclusions and Relevance: The findings of this study suggest that selective thalamic vulnerability may have chronic neuronal consequences with relevance to long-term outcome, suggesting the evolving and potentially lifelong thalamic neuronal consequences of TBI. FMZ PET is a more sensitive marker of the burden of neuronal injury than routine imaging; therefore, it could inform outcome prognostication and may lead to the development of individualized precision medicine approaches.

Life Cycle Assessment and Net Energy Analysis of an Integrated Hydrothermal Liquefaction-Anaerobic Digestion of Single and Mixed Beverage Waste and Sewage Sludge.

The conversion of biomass to bioenergy is one of the approaches to creating a sustainable society. In this study, the life cycle assessment and the net energy analysis of converting mixed sewage sludge and beverage waste into bioenergy via a combined hydrothermal liquefaction-anaerobic digestion (HTL-AD) system was carried out. Primary sludge (PS), winery rose lees (RL), brewery Trub (BT), the mixture of brewery trub and primary sludge (BTPS) and the mixture of winery rose lees and primary sludge (RLPS) were the feedstocks considered. Efficient energy utilization [in form of net energy ratio (NER)], and environmental emissions were evaluated. The NER of BT (2.07) and RL (1.76) increased when mixed with PS (3.18) to produce BTPS (3.20) and RLPS (2.85). Also, the HTL phase of the combined HTL-AD system produced a greater NER than the AD phase in BT, BTPS, and PS and vice-versa in RL and RLPS. Six environmental impact categories were studied namely global warming, terrestrial acidification, ionizing radiation, terrestrial ecotoxicity, human carcinogenic toxicity, and human non-carcinogenic toxicity. RL produced the greatest environmental impact while BTPS produced the least impact, thus indicating the advantage of feedstock combination. This study shows that the combination of feedstocks for bioenergy production in an HTL-AD system does not only increase the quality and quantity of products but also increases the overall NER as well as reducting the environmental impacts. The study also proved that an integrated HTL-AD system is an energy efficient system with greater resource utilization and less environmental footprint than the constituent systems.

Development of modular polymeric nanoparticles for drug delivery using amine reactive chemistry.

Curcumin has been explored for its anti-cancer potential, but is severely limited by its hydrophobicity and sensitivity to light and water. In this study, poly (lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) were synthesized to encapsulate curcumin via single emulsion method to improve curcumin stability and bioavailability. The PLGA NPs were coated with oligomeric chitosan (COS) and RGD peptide (a peptide consisting of Arg-Gly-Asp) using amine-reactive chemistry (NHS and EDC). Both COS and RGD had been previously shown to accumulate and target many different types of cancer cells. NPs were characterised based on size distribution, zeta potential, and binding efficiency of RGD peptide. They were also evaluated on encapsulation efficiency, and stability, of curcumin within the NPs. OVCAR-3 cancer cells were treated with COS and RGD-coated PLGA NPs loaded with Coumarin-6 dye for fluorescent imaging of cell uptake. They were also treated with curcumin-loaded NPs to determine cytotoxicity and effectiveness of delivery. The NPs exhibited size distribution and zeta potential within expected values, though binding efficiency of RGD was low. Curcumin-loaded NPs showed significant increase in cytotoxicity over free (unencapsulated) curcumin, and void (empty) NPs, suggesting successful delivery of curcumin as an anti-cancer agent; the performance of COS and RGD coated NPs over bare PLGA NPs was inconclusive, however, optimization will be required to improve formulation during the coating steps. This method of NP synthesis serves as proof of concept for a modular solution to the development of various coated polymeric NPs for other drugs or applications.

Primary Hodgkin Lymphoma of the Breast: A Case Report and Literature Review Examining the Use of Different Chemotherapy Regimens.

Primary classic Hodgkin lymphoma (HL) of the breast is a rare type of breast disease. The diagnosis is mostly confirmed by an excisional biopsy. The first line of treatment commonly used for Hodgkin lymphoma is doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Our case report is about a 48-year-old lady who was diagnosed with bilateral breast Hodgkin lymphoma following an excisional biopsy and was treated with brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (BV-AVD). The patient responded positively after the initiation of the regimen. There is scarce data on the classic Hodgkin lymphoma of the breast, and even with the wide use of first-line treatment using ABVD, the disease is still difficult to manage. Hence, patients with breast masses should be screened for classic HL of the breast, and larger studies are needed to establish specific treatment guidelines concerning HL of the breast to prevent relapse and other complications.

Targeting MERTK on tumour cells and macrophages: a potential intervention for sporadic and NF2-related meningioma and schwannoma tumours.

Meningioma and schwannoma are common tumours of the nervous system. They occur sporadically or as part of the hereditary NF2-related schwannomatosis syndrome. There is an unmet need for new effective drug treatments for both tumour types. In this paper, we demonstrate overexpression/activation of TAM (TYRO3/AXL/MERTK) receptors (TAMs) and overexpression/release of ligand GAS6 in patient-derived meningioma tumour cells and tissue. For the first time, we reveal the formation of MERTK/TYRO3 heterocomplexes in meningioma and schwannoma tissue. We demonstrate the dependence of AXL and TYRO3 expression on MERTK in both tumour types, as well as interdependency of MERTK and AXL expression in meningioma. We show that MERTK and AXL contribute to increased proliferation and survival of meningioma and schwannoma cells, which we inhibited in vitro using the MERTK/FLT3 inhibitor UNC2025 and the AXL inhibitor BGB324. UNC2025 was effective in both tumour types with superior efficacy over BGB324. Finally, we found that TAMs are expressed by tumour-associated macrophages in meningioma and schwannoma tumours and that UNC2025 strongly depleted macrophages in both tumour types.

Strengthening surgical healthcare research capacity in sub-Saharan Africa: impact of a research training programme in Nigeria.

Background: Limited research capacity has contributed to the lack of high-quality research from low-and middle-income countries. This is compounded by limited research training opportunities. Research capacity scale-up training was deployed as part of the implementation of the National Surgical, Obstetrics, Anaesthesia, and Nursing Plan for Nigeria. We report the impact of this locally contextualized efforts to scale up research capacity in sub-Saharan Africa. Methods: This is an evaluation of the training of 65 participants in research, grant writing and manuscript writing and publication. Pre- and post-training surveys using a 5-point Likert scale and open-ended questions were administered to evaluate the impact of the programme. Results: There were 39 (60%) males and 26 (40%) females aged 26-62 years (median 42 years). Thirty-nine (60%) participants had previous training in research, but only 12 (18.5%) had previously received grant writing training, and 17 (26.2%) had previously received manuscript writing and publishing training. Following training, 45 (70.3%) participants agreed that the training was relevant. The research, grant writing and manuscript writing, and publication components of the training were rated high by the participants (45-59, 70.3-92.2%). However, 41.2% felt that there was not enough time, and 32.4% felt that the training was too comprehensive. Nearly all the participants agreed that the training had improved their skills in research, grant writing and manuscript writing and publication, and more than two-thirds subsequently engaged in informal mentoring of others. Overall, participants achieved success in designing their own research projects and publishing manuscripts and grants. Three (4.6%) of the participants had gone on to become faculty for the research training programme. The three top barriers encountered following training were time constraints (67.3%), lack of funding (36.5%) and not being able to find research collaborators (25%). Conclusion: Outcome of this training programme is encouraging and highlights the feasibility and potential impact of deploying such programmes in low and middle income countries (LMICs). Despite the positive outcomes, barriers including time constraints, funding limitations, and difficulties in finding research collaborators remain to be addressed. Such training programmes need to be supported to strengthen the research capacity in this and similar settings.

Cognitive Motor Dissociation in Disorders of Consciousness.

BACKGROUND: Patients with brain injury who are unresponsive to commands may perform cognitive tasks that are detected on functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). This phenomenon, known as cognitive motor dissociation, has not been systematically studied in a large cohort of persons with disorders of consciousness. METHODS: In this prospective cohort study conducted at six international centers, we collected clinical, behavioral, and task-based fMRI and EEG data from a convenience sample of 353 adults with disorders of consciousness. We assessed the response to commands on task-based fMRI or EEG in participants without an observable response to verbal commands (i.e., those with a behavioral diagnosis of coma, vegetative state, or minimally conscious state-minus) and in participants with an observable response to verbal commands. The presence or absence of an observable response to commands was assessed with the use of the Coma Recovery Scale-Revised (CRS-R). RESULTS: Data from fMRI only or EEG only were available for 65% of the participants, and data from both fMRI and EEG were available for 35%. The median age of the participants was 37.9 years, the median time between brain injury and assessment with the CRS-R was 7.9 months (25% of the participants were assessed with the CRS-R within 28 days after injury), and brain trauma was an etiologic factor in 50%. We detected cognitive motor dissociation in 60 of the 241 participants (25%) without an observable response to commands, of whom 11 had been assessed with the use of fMRI only, 13 with the use of EEG only, and 36 with the use of both techniques. Cognitive motor dissociation was associated with younger age, longer time since injury, and brain trauma as an etiologic factor. In contrast, responses on task-based fMRI or EEG occurred in 43 of 112 participants (38%) with an observable response to verbal commands. CONCLUSIONS: Approximately one in four participants without an observable response to commands performed a cognitive task on fMRI or EEG as compared with one in three participants with an observable response to commands. (Funded by the James S. McDonnell Foundation and others.).

Long-Term Outcomes of Cochlear Implantation in Usher Syndrome.

OBJECTIVES: Usher syndrome (USH), characterized by bilateral sensorineural hearing loss (SNHL) and retinitis pigmentosa (RP), prompts increased reliance on hearing due to progressive visual deterioration. It can be categorized into three subtypes: USH type 1 (USH1), characterized by severe to profound congenital SNHL, childhood-onset RP, and vestibular areflexia; USH type 2 (USH2), presenting with moderate to severe progressive SNHL and RP onset in the second decade, with or without vestibular dysfunction; and USH type 3 (USH3), featuring variable progressive SNHL beginning in childhood, variable RP onset, and diverse vestibular function. Previous studies evaluating cochlear implant (CI) outcomes in individuals with USH used varying or short follow-up durations, while others did not evaluate outcomes for each subtype separately. This study evaluates long-term CI performance in subjects with USH, at both short-term and long-term, considering each subtype separately. DESIGN: This retrospective, observational cohort study identified 36 CI recipients (53 ears) who were categorized into four different groups: early-implanted USH1 (first CI at ≤7 years of age), late-implanted USH1 (first CI at ≥8 years of age), USH2 and USH3. Phoneme scores at 65 dB SPL with CI were evaluated at 1 year, ≥2 years (mid-term), and ≥5 years postimplantation (long-term). Each subtype was analyzed separately due to the significant variability in phenotype observed among the three subtypes. RESULTS: Early-implanted USH1-subjects (N = 23 ears) achieved excellent long-term phoneme scores (100% [interquartile ranges {IQR} = 95 to 100]), with younger age at implantation significantly correlating with better CI outcomes. Simultaneously implanted subjects had significantly better outcomes than sequentially implanted subjects ( p = 0.028). Late-implanted USH1 subjects (N = 3 ears) used CI solely for sound detection and showed a mean phoneme discrimination score of 12% (IQR = 0 to 12), while still expressing satisfaction with ambient sound detection. In the USH2 group (N = 23 ears), a long-term mean phoneme score of 85% (IQR = 81 to 95) was found. Better outcomes were associated with younger age at implantation and higher preimplantation speech perception scores. USH3-subjects (N = 7 ears) achieved a mean postimplantation phoneme score of 71% (IQR = 45 to 91). CONCLUSIONS: This study is currently one of the largest and most comprehensive studies evaluating CI outcomes in individuals with USH, demonstrating that overall, individuals with USH benefit from CI at both short- and long-term follow-up. Due to the considerable variability in phenotype observed among the three subtypes, each subtype was analyzed separately, resulting in smaller sample sizes. For USH1 subjects, optimal CI outcomes are expected with early simultaneous bilateral implantation. Late implantation in USH1 provides signaling function, but achieved speech recognition is insufficient for oral communication. In USH2 and USH3, favorable CI outcomes are expected, especially if individuals exhibit sufficient speech recognition with hearing aids and receive ample auditory stimulation preimplantation. Early implantation is recommended for USH2, given the progressive nature of hearing loss and concomitant severe visual impairment. In comparison with USH2, predicting outcomes in USH3 remains challenging due to the variability found. Counseling for USH2 and USH3 should highlight early implantation benefits and encourage hearing aid use.

A synergistic workspace for human consciousness revealed by Integrated Information Decomposition.

How is the information-processing architecture of the human brain organised, and how does its organisation support consciousness? Here, we combine network science and a rigorous information-theoretic notion of synergy to delineate a 'synergistic global workspace', comprising gateway regions that gather synergistic information from specialised modules across the human brain. This information is then integrated within the workspace and widely distributed via broadcaster regions. Through functional MRI analysis, we show that gateway regions of the synergistic workspace correspond to the human brain's default mode network, whereas broadcasters coincide with the executive control network. We find that loss of consciousness due to general anaesthesia or disorders of consciousness corresponds to diminished ability of the synergistic workspace to integrate information, which is restored upon recovery. Thus, loss of consciousness coincides with a breakdown of information integration within the synergistic workspace of the human brain. This work contributes to conceptual and empirical reconciliation between two prominent scientific theories of consciousness, the Global Neuronal Workspace and Integrated Information Theory, while also advancing our understanding of how the human brain supports consciousness through the synergistic integration of information.

The human brain consists of billions of neurons which process sensory inputs, such as sight and sound, and combines them with information already stored in the brain. This integration of information guides our decisions, thoughts, and movements, and is hypothesized to be integral to consciousness. However, it is poorly understood how the brain regions responsible for processing this integration are organized in the brain. To investigate this question, Luppi et al. employed a mathematical framework called Partial Information Decomposition (PID) which can distinguish different types of information: redundancy (available from many regions) and synergy (which reflects genuine integration). The team applied the PID framework to the brain scans of 100 individuals. This allowed them to identify which brain regions combine information from across the brain (known as gateways), and which ones transmit it back to the rest of the brain (known as broadcasters). Next, Luppi et al. set out to find how these regions compared in unconscious and conscious individuals. To do this, they studied 15 healthy volunteers whose brains were scanned (using a technique called functional MRI) before, during, and after anaesthesia. This revealed that the brain integrated less information when unconscious, and that this reduction happens predominantly in gateway rather than broadcaster regions. The same effect was also observed in the brains of individuals who were permanently unconscious due to brain injuries. These findings provide a way of understanding how information is organised in the brain. They also suggest that loss of consciousness due to brain injuries and anaesthesia involve similar brain circuits. This means it may be possible to gain insights about disorders of consciousness from studying how people emerge from anaesthesia.

Admission Cardiotocography and Neonatal Outcomes at a Tertiary Health Facility in Southwestern Nigeria.

BACKGROUND: Admission cardiotocography (CTG), a noninvasive procedure, is used to indicate the state of oxygenation of the fetus on admission into the labor ward. OBJECTIVE: This study assessed the association of admission CTG findings with neonatal outcome at a tertiary health facility. MATERIALS AND METHODS: A prospective, observational study of 206 pregnant women who were admitted into the labor ward with singleton live pregnancies. Information on the demographic characteristics, obstetrics and medical history, admission CTG tracing, and neonatal outcome was obtained using a structured data collection form. Data were analyzed using the SPSS software version 20.0 with the level of significance set at P < 0.05. RESULTS: The admission CTG findings were normal in 73.3%, suspicious in 13.6%, and pathological in 13.1% of the women. The occurrence of low birth weight, special care baby unit (SCBU) admission, asphyxiated neonates, neonatal death, and prolonged hospital admission was significantly more frequent among those with pathological admission CTG results compared with normal and suspicious results (P < 0.05). The incidence of vaginal delivery was more common when the CTG findings were normal, whereas all women with pathological CTG result had a cesarean delivery. CONCLUSION: Admission CTG was effective in identifying fetuses with a higher incidence of perinatal asphyxia. Neonatal outcome such as low birth weight, APGAR score, SCBU admission, and prolonged hospital admission was significantly associated with pathological CTG findings. In the absence of facilities for further investigations, prompt intervention for delivery should be ensured if admission CTG is pathological.

Résumé Contexte:La cardiotocographie d'admission (CTG), une procédure non invasive, est utilisée pour indiquer l'état d'oxygénation du fœtus lors de son admission en salle de travail.Objectif:Cette étude a évalué l'association entre les résultats du CTG à l'admission et l'issue néonatale dans un établissement de santé tertiaire.Matériels et méthodes:Une étude observationnelle prospective portant sur 206 femmes enceintes admises en salle de travail avec des grossesses vivantes uniques. Des informations sur les caractéristiques démographiques, les antécédents obstétricaux et médicaux, le traçage CTG à l'admission et les résultats néonatals ont été obtenues à l'aide d'un formulaire de collecte de données structuré. Les données ont été analysées à l'aide du logiciel SPSS version 20.0 avec le niveau de signification fixé à P <0,05.Résultats:Les résultats du CTG à l'admission étaient normaux chez 73,3 %, suspects chez 13,6 % et pathologiques chez 13,1 % des femmes. La survenue d'un faible poids à la naissance, d'une admission dans une unité de soins spéciaux pour bébés (SCBU), de nouveau-nés asphyxiés, de décès néonatals et d'une hospitalisation prolongée était significativement plus fréquente chez les personnes ayant des résultats CTG d'admission pathologiques par rapport aux résultats normaux et suspects (P < 0,05). L'incidence des accouchements par voie basse était plus fréquente lorsque les résultats du CTG étaient normaux, alors que toutes les femmes présentant un résultat pathologique du CTG avaient accouché par césarienne.Conclusion:L'admission CTG s'est avérée efficace pour identifier les fœtus présentant une incidence plus élevée d'asphyxie périnatale. Les résultats néonatals tels qu'un faible poids à la naissance, le score APGAR, l'admission au SCBU et l'hospitalisation prolongée étaient significativement associés aux résultats pathologiques du CTG. En l'absence de moyens permettant des investigations plus approfondies, une intervention rapide pour l'accouchement doit être assurée si l'admission du CTG est pathologique.

A roadmap for clinical trials in MASH-related compensated cirrhosis.

Although metabolic dysfunction-associated steatohepatitis (MASH) is rapidly becoming a leading cause of cirrhosis worldwide, therapeutic options are limited and the number of clinical trials in MASH-related compensated cirrhosis is low as compared to those conducted in earlier disease stages. Moreover, designing clinical trials in MASH cirrhosis presents a series of challenges regarding the understanding and conceptualization of the natural history, regulatory considerations, inclusion criteria, recruitment, end points and trial duration, among others. The first international workshop on the state of the art and future direction of clinical trials in MASH-related compensated cirrhosis was held in April 2023 at Vall d'Hebron University Hospital in Barcelona (Spain) and was attended by a group of international experts on clinical trials from academia, regulatory agencies and industry, encompassing expertise in MASH, cirrhosis, portal hypertension, and regulatory affairs. The presented Roadmap summarizes important content of the workshop on current status, regulatory requirements and end points in MASH-related compensated cirrhosis clinical trials, exploring alternative study designs and highlighting the challenges that should be considered for upcoming studies on MASH cirrhosis.

Repeat traumatic brain injury exacerbates acute thalamic hyperconnectivity in humans.

Repeated mild traumatic brain injury is of growing interest regarding public and sporting safety and is thought to have greater adverse or cumulative neurological effects when compared with single injury. While epidemiological links between repeated traumatic brain injury and outcome have been investigated in humans, exploration of its mechanistic substrates has been largely undertaken in animal models. We compared acute neurological effects of repeat mild traumatic brain injury (n = 21) to that of single injury (n = 21) and healthy controls (n = 76) using resting-state functional MRI and quantified thalamic functional connectivity, given previous identification of its prognostic potential in human mild traumatic brain injury and rodent repeat mild traumatic brain injury. Acute thalamocortical functional connectivity showed a rank-based trend of increasing connectivity with number of injuries, at local and global scales of investigation. Thus, history of as few as two previous injuries can induce a vulnerable neural environment of exacerbated hyperconnectivity, in otherwise healthy individuals from non-specialist populations. These results further establish thalamocortical functional connectivity as a scalable marker of acute injury and long-term neural dysfunction following mild traumatic brain injury.

Transgender Health Dilemmas: An Intersectional Analysis of the Therapeutic Itineraries of Transgender Communities in the Philippines.

This study leverages an intersectional lens to characterize the therapeutic itineraries of local transgender (trans) communities vis-à-vis salient cisnormative and capitalist structures in Philippine society that produce trans health inequities. Interpretative phenomenological analysis of online interviews with thirteen (13) self-identified trans Filipinos reveals how the inaccessibility of trans-responsive care in the Philippines fosters trans health dilemmas, or the dilemmatic decision-making circumstances and processes that force trans Filipinos to choose between their trans-specific health needs and other needs. Such dilemmas valorize the deprioritization of trans health, disengagement with the health system, and the pursuit of alternative pathways to care oftentimes at the expense of their overall well-being. Addressing these dilemmas entails research, policy, and advocacy work that contend with the implicated structures of domination through systemic interventions initiated in partnership with local trans communities.

Clinicopathological study of otomycosis in a tertiary hospital in South-west Nigeria.

Background: Otomycosis is common in environments with hot, humid weather, and it may be challenging to manage. Objectives: To profile common clinical presentations, the pathogenic fungi, the treatment modalities with responses, and explore clinical factors associated with having positive fungal culture in Otomycosis. Methods: Retrospective review of patients with Otomycosis. Demographic and clinical parameters, otoscopic findings and mycological study results were recorded. The treatment modalities used and treatment response were summarized. Comparative statistical analyses of associated factors to positive fungal culture were performed with Chi square test, and Student's t-test, using SPSS version 22.0. Results: Total of 71 patients with M: F=1:1.8, mean age 38.5±19.8 years. Average duration of symptoms was 5.4 ±4.6 weeks; common presenting complaint was itchy ear (33.8%). Majority of patients (85.9%) had unilateral ear involvement, 50.0% applied ototopic medications before presentation, 8.5% had multiple co-morbidities. 20 patients had positive fungal culture results; common fungal isolate was Aspergillus niger 9 (45.0%).Clinical factors associated with positive culture of fungus were age, non-previous use of ototopic drugs, and presence of co-morbidity. The most common treatment was local ear debridement and use of topical antifungal creams. Majority (91.5%) of the patients responded with resolution of fungal infection. Complications rate was 8.4%. Conclusions: Otomycosis commonly present with itchy ears, the pathogenic fungi commonly being Aspergillus species. The factors associated with positive fungal culture were age, non-usage of ototopic agents and presence of co-morbidity. Treatment modality used was local debridement and topical antifungal agents, which produced favourable response in most patients.

Knowledge and management of female genital schistosomiasis in sub-Saharan Africa: A scoping review protocol.

Background: Approximately 20 to 120 million women of reproductive age worldwide are thought to be affected by female genital schistosomiasis (FGS). It is a preventable manifestation of schistosomiasis in adolescent girls and women, which remains underreported, underdiagnosed, or misdiagnosed, and largely untreated. Objective: This study aimed to map evidence on the knowledge and management of FGS from 1950 to 2022 in sub-Saharan Africa. Method: The Arksey and O'Malley and Levac et al. framework suggestions and a guideline from Joanna Briggs Institute will be employed. Search for literature will be in PubMed, Scopus, Cochrane, Web of Science, MEDLINE via PubMed, and Google Scholar from 1950 to 2022 for useful published research articles using key phrases or search terms and grey literature with limitations for studies conducted in sub-Saharan Africa. Two reviewers will screen the articles. Kappa coefficients by Cohen statistics will be computed for inter-screener agreement, and the selected articles will be evaluated using Mixed Method Appraisal Tool (MMAT). Results: The researchers will map and explore the evidence of the knowledge and management of FGS in the subregion. The years of publications, countries of study, and settings will be reported, and the identified research gaps will be reported. Conclusion: The researchers anticipate that this study will determine and map the evidence on the knowledge and management of FGS in sub-Saharan Africa; identify knowledge and management gaps, and direct future research. Contribution: This study will add to the literature on FGS and direct future research regarding the knowledge and management of FGS.

Comparison of plasma clearance of [51Cr]CrEDTA based on three, two and single samples to measure the glomerular filtration rate in patients with solid tumors: a prospective cross-sectional analysis.

OBJECTIVES: [51Cr]CrEDTA is used to measure the Glomerular Filtration Rate (GFR) in different clinical conditions. However, there is no consensus on the ideal number of blood samples to be taken and at what time points to measure its clearance. This study aimed to compare Slope Intercept (SI) and Single-Sample (SS) methods for measuring GFR in patients with solid tumors, stratified by age, GFR, and Body Mass Index (BMI). METHODS: 1,174 patients with cancer were enrolled in this prospective study. GFR was calculated by the SI method using blood samples drawn 2-, 4-, and 6-hours after [51Cr]CrEDTA injection (246-GFR). GFR was also measured using the SI method with samples at 2 and 4 hours (24-GFR) and at 4 and 6 hours (46-GFR), and SS methods according to Groth (4Gr-GFR) and Fleming (4Fl-GFR). Statistical analysis was performed to assess the accuracy, precision, and bias of the methods. RESULTS: Mean 246-GFR was 79.2 ± 21.9 mL/min/1.73 m2. ANOVA indicated a significant difference between 4Gr-GFR and the reference 246-GFR. Bias was lower than 5 mL/min/1.73 m2 for all methods, except for SS methods in subgroups BMI > 40 kg/m2; GFR > 105 or < 45. Precision was adequate and accuracy of 30 % was above 98% for all methods, except for SS methods in subgroup GFR < 45. CONCLUSION: 46-GFR and 246-GFR have high agreement and may be used to evaluate kidney function in patients with solid tumors. Single-sample methods can be adopted in specific situations, for non-obese patients with expected normal GFR.