The protective role of two oxindole derivatives is mediated by modulating NLRP3/caspase-1 and PI3K/AKT pathways in a preclinical animal model of hepatic ischemia reperfusion injury.

Aim Hepatic ischemia reperfusion injury (HIRI) is a leading cause of mortality post liver transplantation, hypovolemic shock and trauma. In this study, we tested, on molecular bases, the possible protective role of two different derivatives of 2-oxindole in a preclinical model of HIRI in rats. MAIN METHODS: HIRI was operated in male Wistar albino rats and prophylactic treatment with oxindole-curcumin (Coxi) or oxindole-vanillin (Voxi) was carried out before the operation. The biochemical and histopathological investigations, in addition to the mechanistic characterizations of the effect of the tested drugs were performed. KEY FINDINGS: HIRI was assured with elevated liver enzymes and marked changes in histopathological features, inflammatory response and oxidative stress. Pretreatment with Coxi and Voxi improved the hepatic histopathological alterations, reduced the elevated serum liver enzymes level and hepatic Malondialdehyde (MDA) content, increased the hepatic Superoxide Dismutase (SOD) activity and reduced Glutathione (GSH) content, downregulated the expression of TNF-α, IL-6, Nod-Like Receptor p3 (NLRP3), Cleaved caspase1, Cleaved caspase 3 proteins, alongside the expression level of IL-1ß, ICAM-1, VCAM-1 and BAX genes, attenuated NF-кB p-P65 Ser536 and Myeloperoxidase (MPO)-positive neutrophils, and activated the PI3K/AKT pathway. SIGNIFICANCE: Coxi and Voxi have promising hepatoprotective activity against HIRI in rats through ameliorating the biochemical and histopathological alterations, attenuating inflammatory and oxidative stress status by modulating the inflammatory TNF-α/ICAM-1, the pyroptosis NLRP3/Caspase-1, and the antioxidant PI3K/AKT pathways.

Design and synthesis of new dihydropyrimidine/sulphonamide hybrids as promising anti-inflammatory agents via dual mPGES-1/5-LOX inhibition.

A novel series of dihydropyrimidine/sulphonamide hybrids 3a-j with anti-inflammatory properties have been developed and tested as dual mPGES-1/5-LOX inhibitors. In vitro assay, results showed that compounds 3c, 3e, 3h, and 3j were the most effective dual inhibitors of mPGES-1 and 5-LOX activities. Compound 3j was the most potent dual inhibitor with IC50 values of 0.92 µM and 1.98 µM, respectively. In vivo, anti-inflammatory studies demonstrated that compounds 3c, 3e, 3h, and 3e had considerable anti-inflammatory activity, with EI% ranging from 29% to 71%. Compounds 3e and 3j were equivalent to celecoxib after the first hour but exhibited stronger anti-inflammatory effects than celecoxib after the third and fifth hours. Moreover, compounds 3e and 3j significantly reduced the levels of pro-inflammatory cytokines (PGE2, TNF-α, and IL-6) with gastrointestinal safety profiles. Molecular docking simulations explored the most potent derivatives' binding affinities and interaction patterns within mPGES-1 and 5-LOX active sites. This study disclosed that compound 3j is a promising anti-inflammatory lead with dual mPGES-1/5-LOX inhibition that deserves further preclinical investigation.

Discovery and Anticancer Screening of Novel Oxindole-Based Derivative Bearing Pyridyl Group as Potent and Selective Dual FLT3/CDK2 Kinase Inhibitor.

Protein kinases regulate cellular activities and make up over 60% of oncoproteins and proto-oncoproteins. Among these kinases, FLT3 is a member of class III receptor tyrosine kinase family which is abundantly expressed in individuals with acute leukemia. Our previous oxindole-based hit has a particular affinity toward FLT3 (IC50 = 2.49 µM) and has demonstrated selectivity towards FLT3 ITD-mutated MV4-11 AML cells, with an IC50 of 4.3 µM. By utilizing the scaffold of the previous hit, sixteen new compounds were synthesized and screened against NCI-60 human cancer cell lines. This leads to the discovery of a potent antiproliferative compound, namely 5l, with an average GI50 value against leukemia and colon cancer subpanels equalling 3.39 and 5.97 µM, respectively. Screening against a specific set of 10 kinases that are associated with carcinogenesis indicates that compound 5l has a potent FLT3 inhibition (IC50 = 36.21 ± 1.07 nM). Remarkably, compound 5l was three times more effective as a CDK2 inhibitor (IC50 = 8.17 ± 0.32 nM) compared to sunitinib (IC50 = 27.90 ± 1.80 nM). Compound 5l was further analyzed by means of docking and molecular dynamics simulation for CDK2 and FLT3 active sites which provided a rational for the observed strong inhibition of kinases. These results suggest a novel structural scaffold candidate that simultaneously inhibits CDK2 and FLT3 and gives encouragement for further development as a potential therapeutic for leukemia and colon cancer.

Integrated management of groundwater quantity, physicochemical properties, and microbial quality in West Nile delta using a new MATLAB code and geographic information system mapping.

Groundwater is an excellent alternative to freshwater for drinking, irrigation, and developing arid regions. Agricultural, commercial, industrial, residential, and municipal activities may affect groundwater quantity and quality. Therefore, we aimed to use advanced methods/techniques to monitor the piezometric levels and collect groundwater samples to test their physicochemical and biological characteristics. Our results using software programs showed two main types of groundwater: the most prevalent was the Na-Cl type, which accounts for 94% of the groundwater samples, whereas the Mg-Cl type was found in 6% of samples only. In general, the hydraulic gradient values, ranging from medium to low, could be attributed to the slow movement of groundwater. Salinity distribution in groundwater maps varied between 238 and 1350 mg L-1. Although lower salinity values were observed in northwestern wells, higher values were recorded in southern ones. The collected seventeen water samples exhibited brackish characteristics and were subjected to microbial growth monitoring. Sample WD12 had the lowest total bacterial count (TBC) of 4.8 ± 0.9 colony forming unit (CFU mg L-1), while WD14 had the highest TBC (7.5 ± 0.5 CFU mg L-1). None of the tested water samples, however, contained pathogenic microorganisms. In conclusion, the current simulation models for groundwater drawdown of the Quaternary aquifer system predict a considerable drawdown of water levels over the next 10, 20, and 30 years with the continuous development of the region.

New 2-oxoindole derivatives as multiple PDGFRα/ß and VEGFR-2 tyrosine kinase inhibitors.

Two new series of N-aryl acetamides 6a-o and benzyloxy benzylidenes 9a-p based 2-oxoindole derivatives were designed as potent antiproliferative multiple kinase inhibitors. The results of one-dose NCI antiproliferative screening for compounds 6a-o and 9a-p elucidated that the most promising antiproliferative scaffolds were 6f and 9f, which underwent five-dose testing. Notably, the amido congener 6f was the most potent derivative towards pancreatic ductal adenocarcinoma MDA-PATC53 and PL45 cell lines (IC50 = 1.73 µM and 2.40 µM, respectively), and the benzyloxy derivative 9f was the next potent one with IC50 values of 2.85 µM and 2.96 µM, respectively. Both compounds 6f and 9f demonstrated a favorable safety profile when tested against normal prostate epithelial cells (RWPE-1). Additionally, compound 6f displayed exceptional selectivity as a multiple kinase inhibitor, particularly targeting PDGFRα, PDGFRß, and VEGFR-2 kinases, with IC50 values of 7.41 nM, 6.18 nM, and 7.49 nM, respectively. In contrast, the reference compound Sunitinib exhibited IC50 values of 43.88 nM, 2.13 nM, and 78.46 nM against the same kinases. The derivative 9f followed closely, with IC50 values of 9.9 nM, 6.62 nM, and 22.21 nM for the respective kinases. Both 6f and 9f disrupt the G2/M cell cycle transition by upregulating p21 and reducing CDK1 and cyclin B1 mRNA levels. The interplay between targeted kinases and these cell cycle regulators underpins the G2/M cell cycle arrest induced by our compounds. Also, compounds 6f and 9f fundamentally resulted in entering MDA-PATC53 cells into the early stage of apoptosis with good percentages compared to the positive control Sunitinib. The in silico molecular-docking outcomes of scaffolds 6a-o and 9a-p in VEGFR-2, PDGFRα, and PDGFRß active sites depicted their ability to adopt essential binding interactions like the reference Sunitinib. Our designed analogs, specifically 6f and 9f, possess promising antiproliferative and kinase inhibitory properties, making them potential candidates for further therapeutic development.

Impact of Transplantation Timing on Renal Graft Survival Outcomes and Perioperative Complications.

Nighttime organ transplantation aims to decrease cold ischemia duration, yet conflicting data exists on its impact on graft function and perioperative complications. This multicenter TRANSPLANT'AFUF study including 2,854 patients, transplanted between 1 January 2011, and 31 December 2022, investigated nighttime kidney transplantation's impact (8:00 p.m.-8:00 a.m.) versus daytime (8:00 a.m.-8:00 p.m.) on surgical complications and graft survival. Overall, 2043 patients (71.6%) underwent daytime graft, while 811 (28.4%) underwent nighttime graft. No impact was observed of timing of graft surgery on graft survival with a median survival of 98 months and 132 months for daytime and nightime grafting, respectively (p = 0.1749). Moreover, no impact was observed on early surgical complications (Clavien I-II = 20.95% for DG and 20.10% for NG; Clavien III-IV-V = 15.42% for DG and 12.94% for NG; p = 0.0889) and late complications (>30 days) (Clavien I-II = 6.80% for DG and 5.67% for NG; Clavien III-IV-V = 12.78% for DG and 12.82% for NG; p = 0.2444). Noteworthy, we found a significant increase in Maastricht 3 donors' rates in nighttime transplantation (5.53% DG vs. 21.45% NG; p < 0.0001). In conclusion, nighttime kidney transplantation did not impact early/late surgical complications nor graft survival.

A genetic component in Chiari I malformation: Chiari 1 malformation in all five family members.

Under certain classifications, a Chiari type I (CMI) malformation can be characterized as a herniation of the cerebellar tonsils greater than 3 mm. Patients with CMI often have a smaller posterior fossa volume, which results in a smaller amount of space for the cerebellum, leading to the herniation of the cerebellar tonsils through the foramen magnum. Although inheritable factors such as posterior fossa volume can be traced to specific genes, there has not been a gene that can be attributed to directly causing CMI. However, several cases of CMI have exhibited a familial inheritance pattern. There are mixed findings regarding the exact nature of its inheritance, with some papers arguing in favor of an autosomal dominant pattern. In this case series, we detail a mother, father, and all 3 of their children diagnosed with CMI. Previous literature has not included both a mother and father with CMI.

Dietary Paenibacillus polymyxa AM20 as a new probiotic: Improving effects on IR broiler growth performance, hepatosomatic index, thyroid hormones, lipid profile, immune response, antioxidant parameters, and caecal microorganisms.

The search for a natural antimicrobial agent is ongoing and critical because of the rise and rapid proliferation of antibiotic-resistant pathogenic bacteria. The current study aims to examine the effect of Paenibacillus polymyxa AM20 as an alternative antibiotic and feed additive on Indian river broiler performance, digestive enzymes, thyroid hormones, lipid profile, hepatosomatic index, immunological response, gut bacteria, and antioxidant parameters. The bacterial isolate AM20 was identified at the gene level by isolating DNA and using PCR to detect genes. Based on 16S rRNA gene sequence analysis, the bacterial isolate was identified as Paenibacillus polymyxa. One hundred twenty Indian river broilers (1-day old) were randomly divided into 4 groups of 10 chicks each, with 3 replicates. The control group was fed a basal diet only, while the other 3 were administered control diets supplemented with P. polymyxa at 3 concentrations: 0.5, 1, and 1.5 mg/kg. The findings revealed that all groups that received graded amounts of P. polymyxa increased all growth parameters throughout the study. P. polymyxa treatment at 1.5 mg/kg increased body gain by 9% compared to the control due to increased feed intake (P = 0.0001), growth rate (P = 0.0001), and decreased feed conversion ratio. Compared to the control group, P. polymyxa (1.5 mg/kg) enhanced kidney functions in chickens by reducing uric acid and creatinine levels (P = 0.0451). Compared to the control group, alanine aminotransferase and aspartate transaminase levels in the liver were significantly reduced at all P. polymyxa doses. Liver function values were highest for P. polymyxa at 1.5 mg/kg. Compared to the control group, those whose diets included P. polymyxa had significantly better blood cholesterol levels, high-density lipoprotein, low-density lipoprotein, immunological response, thyroid function, and gut microbiota. In general, broiler chickens' economic efficiency was improved by including P. polymyxa in their diet, which also improved their growth performance, carcass dressing, specific blood biochemical levels and enzymes, and the composition of the gut microbiota.

Indole-based FLT3 inhibitors and related scaffolds as potential therapeutic agents for acute myeloid leukemia.

Fms-like tyrosine kinase 3 (FLT3) mutation mechanisms are among the most common genetic abnormalities detected in about 30% of acute myeloid leukemia (AML) patients. These mutations are accompanied by poor clinical response, although all these progressions in identifying and interpreting biological AML bio-targets. Several small structured FLT3 inhibitors have been ameliorated to struggle against AML. Despite all these developments regarding these inhibitors, the Overall survival rate is about five years or more in less than one-third of diagnosed AML patients. Midostaurin was the first FDA-approved FLT3 inhibitor in 2017 in the United States and Europe for AML remedy. Next, Gilteritinib was an FDA-approved FLT3 inhibitor in 2018 and in the next year, Quizartinib was approved an as FLT3 inhibitor in Japan. Interestingly, indole-based motifs had risen as advantaged scaffolds with unusual multiple kinase inhibitory activity. This review summarises indole-based FLT3 inhibitors and related scaffolds, including FDA-approved drugs, clinical candidates, and other bioactive compounds. Furthermore, their chemotypes, mechanism of action, and interaction mode over both wild and mutated FLT3 target proteins had been judgmentally discussed. Therefore, this review could offer inspiring future perspectives into the finding of new FLT3-related AML therapies.

Neuroanatomical Localization of the Vestibular Cortex: A Case Report.

Vertigo, a symptom of illusory movement, is caused by asymmetry of the vestibular system. The vestibular system consists of the vestibular labyrinth, cranial nerve VIII, brainstem vestibular nuclei, cerebellum, ocular motor nuclei, spinal cord, and less well-defined cerebral projections. In this day and age of artificial intelligence, machine learning, advanced imaging, and cutting-edge research in the field of neurology, the exact cortical control of vestibular function is still uncharted. A 45-year-old woman with a past medical history of labyrinthitis about 4.5 years ago (resolved) presented to hospital due to severe dizziness, emesis, and mild vertical diplopia for the past few days. Her symptom of dizziness i.e. room spinning was continuous without any postural component. MRI of the brain revealed a small stroke in the left hippocampal area, more specifically alveus of hippocampus. The patient was started on dual antiplatelet therapy and atorvastatin for secondary stroke prevention. Follow-up visit as an outpatient at one-month post hospital discharge was unremarkable without any recurrence of vertigo symptoms. We believe this may indicate that the limbic lobe has a much larger role in vestibular functioning than previously thought, and may control more vestibular operations than any other central nervous system area.

Combination of an Oxindole Derivative with (-)-ß-Elemene Alters Cell Death Pathways in FLT3/ITD+ Acute Myeloid Leukemia Cells.

Acute myeloid leukemia (AML) is one of the cancers that grow most aggressively. The challenges in AML management are huge, despite many treatment options. Mutations in FLT3 tyrosine kinase receptors make the currently available therapies less responsive. Therefore, there is a need to find new lead molecules that can specifically target mutated FLT3 to block growth factor signaling and inhibit AML cell proliferation. Our previous studies on FLT3-mutated AML cells demonstrated that ß-elemene and compound 5a showed strong inhibition of proliferation by blocking the mutated FLT3 receptor and altering the key apoptotic genes responsible for apoptosis. Furthermore, we hypothesized that both ß-elemene and compound 5a could be therapeutically effective. Therefore, combining these drugs against mutated FLT3 cells could be promising. In this context, dose-matrix combination-based cellular inhibition analyses, cell morphology studies and profiling of 43 different apoptotic protein targets via combinatorial treatment were performed. Our studies provide strong evidence for the hypothesis that ß-elemene and compound 5a combination considerably increased the therapeutic potential of both compounds by enhancing the activation of several key targets implicated in AML cell death.

Scalp, Oral, and Nail Pemphigus Vulgaris: Clinical Characteristics and a Review of the Literature.

Pemphigus vulgaris (PV) is a rare disease that affects the skin and mucous membranes, causing blistering and erosions. Identifying and effectively managing atypical presentations of pemphigus vulgaris can be challenging due to its rarity. We describe a 32-year-old male patient with a medical history including prediabetes, moderate asthma, hyperlipidemia, coccidioidomycosis, and respiratory infections. He was evaluated via telehealth in the allergy and immunology clinic for uncontrolled asthma. Initially, he complained of a whitish film in the mouth while on treatment with fluticasone and salmeterol. He also noted new vesicular lesions on his scalp and body. When evaluated later in the clinic, he was found to have oral and periungual erosions as well as paronychia. After promptly referring to dermatology, histopathological examination and direct immunofluorescence testing were performed on the patient's lesions, revealing changes consistent with PV. Treatment with prednisone and rituximab resulted in the complete resolution of the patient's bullae and nail deformities over several months. This case highlights the importance of a thorough evaluation of complex medical histories and diagnostic testing in managing asthma and allergy symptoms. It also emphasizes the need for a multidisciplinary approach involving specialists such as immunologists, dermatologists, and infectious disease experts in the diagnosis and management of complex cases.

Biochemical and histopathological effects of copper oxide nanoparticles exposure on the bivalve Chambardia rubens (Lamarck, 1819).

Copper nanoparticles are widely incorporated into many applications, including air and liquid filters, wood preservatives, batteries, thermal and electrical conductivity, inks and skin products. Their potential toxicity and environmental fate, however, are poorly studied in the freshwater bivalves. The aim of the present study was to evaluate the different effects of copper oxide nanoparticles and ionic copper on the digestive glands and gills of the mussel Chambardia rubens. Mussels were treated with 100 and 1000 µg Cu L-1 of copper oxide nanoparticles (CuONPs) or ionic copper (Cu2+) for 3, 7, and 14 days. The Cu accumulation and markers of oxidative stress in the digestive glands and gills were evaluated. The results show that the digestive gland collected higher levels of the two forms of copper than the gills. Exposure to CuONPs or Cu2+ induced significant elevations in superoxide dismutase, glutathione peroxidase and lipid peroxidation. Notably, a significant decrease was observed in the glutathione levels after exposure to both copper forms. CuONPs only induced a significant increase in glutathione reductase and glutathione S-transferase. The ionic copper only induced a significant decrease in catalase activities in the gill tissues. Overall, CuONPs and Cu2+ provoked oxidative stress, and further research is needed to clarify their genotoxic and neurotoxic effects on freshwater mussels and other biota.

Vanillin-Based Indolin-2-one Derivative Bearing a Pyridyl Moiety as a Promising Anti-Breast Cancer Agent via Anti-Estrogenic Activity.

The structure-based design introduced indoles as an essential motif in designing new selective estrogen receptor modulators employed for treating breast cancer. Therefore, here, a series of synthesized vanillin-substituted indolin-2-ones were screened against the NCI-60 cancer cell panel followed by in vivo, in vitro, and in silico studies. Physicochemical parameters were evaluated with HPLC and SwissADME tools. The compounds demonstrated promising anti-cancer activity for the MCF-7 breast cancer cell line (GI = 6-63%). The compound with the highest activity (6j) was selective for the MCF-7 breast cancer cell line (IC50 = 17.01 µM) with no effect on the MCF-12A normal breast cell line supported by real-time cell analysis. A morphological examination of the used cell lines confirmed a cytostatic effect of compound 6j. It inhibited both in vivo and in vitro estrogenic activity, triggering a 38% reduction in uterine weight induced by estrogen in an immature rat model and hindering 62% of ER-α receptors in in vitro settings. In silico molecular docking and molecular dynamics simulation studies supported the stability of the ER-α and compound 6j protein-ligand complex. Herein, we report that indolin-2-one derivative 6j is a promising lead compound for further pharmaceutical formulations as a potential anti-breast cancer drug.

New antiproliferative 3-substituted oxindoles inhibiting EGFR/VEGFR-2 and tubulin polymerization.

New 3-substituted oxindole derivatives were designed and synthesized as antiproliferative agents. The antiproliferative activity of compounds 6a-j was evaluated against 60 NCI cell lines. Among these tested compounds, compounds 6f and 6g showed remarkable antiproliferative activity, specifically against leukemia and breast cancer cell lines. Compound 6f was the most promising antiproliferative agent against MCF-7 (human breast cancer) with an IC50 value of 14.77 µM compared to 5-fluorouracil (5FU) (IC50 = 2.02 µM). Notably, compound 6f hampered receptor tyrosine EGFR fundamentally with an IC50 value of 1.38 µM, compared to the reference sunitinib with an IC50 value of 0.08 µM. Moreover, compound 6f afforded anti-tubulin polymerization activity with an IC50 value of 7.99 µM as an outstanding observable activity compared with the reference combretastatin A4 with an IC50 value of 2.64 µM. In silico molecular-docking results of compound 6f in the ATP-binding site of EGFR agreed with the in vitro results. Besides, the investigation of the physicochemical properties of compound 6f via the egg-boiled method clarified good lipophilicity, GIT absorption, and blood-brain barrier penetration properties.

In silico drug discovery of SIRT2 inhibitors from natural source as anticancer agents.

Sirtuin 2 (SIRT2) is a member of the sirtuin protein family, which includes lysine deacylases that are NAD+-dependent and organize several biological processes. Different forms of cancer have been associated with dysregulation of SIRT2 activity. Hence, identifying potent inhibitors for SIRT2 has piqued considerable attention in the drug discovery community. In the current study, the Natural Products Atlas (NPAtlas) database was mined to hunt potential SIRT2 inhibitors utilizing in silico techniques. Initially, the performance of the employed docking protocol to anticipate ligand-SIRT2 binding mode was assessed according to the accessible experimental data. Based on the predicted docking scores, the most promising NPAtlas molecules were selected and submitted to molecular dynamics (MD) simulations, followed by binding energy computations. Based on the MM-GBSA binding energy estimations over a 200 ns MD course, three NPAtlas compounds, namely NPA009578, NPA006805, and NPA001884, were identified with better ΔGbinding towards SIRT2 protein than the native ligand (SirReal2) with values of - 59.9, - 57.4, - 53.5, and - 49.7 kcal/mol, respectively. On the basis of structural and energetic assessments, the identified NPAtlas compounds were confirmed to be steady over a 200 ns MD course. The drug-likeness and pharmacokinetic characteristics of the identified NPAtlas molecules were anticipated, and robust bioavailability was predicted. Conclusively, the current results propose potent inhibitors for SIRT2 deserving more in vitro/in vivo investigation.

Discovery of oxindole-based FLT3 inhibitors as a promising therapeutic lead for acute myeloid leukemia carrying the oncogenic ITD mutation.

FMS-like tyrosine kinase 3 (FLT3) mutations occur in approximately 30% of acute myeloid leukemia (AML) patients. In the current study, the oxindole chemotype is employed as a structural motif for the design of new FLT3 inhibitors as potential hits for AML irradiation. Cell-based screening was performed with 18 oxindole derivatives and 5a-c inhibited 68%-73% and 83%-91% of internal tandem duplication (ITD)-mutated MV4-11 cell growth for 48- and 72-h treatments while only 0%-2% and 27%-39% in wild-type THP-1 cells. The most potent compound 5a inhibited MV4-11 cells with IC50 of 4.3 µM at 72 h while it was 8.7 µM in THP-1 cells, thus showing two-fold selective inhibition against the oncogenic ITD mutation. The ability of 5a to modulate cell death was examined. High-throughput protein profiling revealed low levels of the growth factors IGFBP-2 and -4 with the blockage of various apoptotic inhibitors such as Survivin. p21 with cellular stress mechanisms was characterized by increased expression of HSP proteins along with TNF-ß. Mechanistically, compounds 5a and 5b inhibited FLT3 kinase with IC50 values of 2.49 and 1.45 µM, respectively. Theoretical docking studies supported the compounds' ability to bind to the FLT3 ATP binding site with the formation of highly stable complexes as evidenced by molecular dynamics simulations. The designed compounds also provide suitable drug candidates with no violation of drug likeability rules.

Wound Healing as an Unconventional Marker for Epilepsy Control in a Patient Experiencing Homelessness: A Case Report.

Post-traumatic epilepsy is a complicated disease that remains challenging to treat even for patients who are able to access care regularly. People experiencing homelessness (PEH) represent a vulnerable demographic for neurologic disorders, especially due to gaps in care, limited resources, and low health literacy. This is a case of a 53-year-old male experiencing homelessness who was encountered by low-resource medical providers in an extra-clinical setting. His medical history was pertinent for a traumatic brain injury at a construction site a few years prior. He was diagnosed with post-traumatic epilepsy but was lost to follow-up due to being homeless and lacking health insurance. He also had a history of multiple hospitalizations secondary to seizures and did not consistently take his anti-epileptic medications. He was noted to have multiple facial wounds of unclear etiology. Upon further investigation, he complained of episodes of waking up on the sidewalk with facial injuries. The high-risk characteristics of his seizures prompted street medicine providers to quickly arrange an appointment with a primary care doctor. The process was further expedited by petitioning other local charitable organizations. He was later connected to a physician and re-prescribed levetiracetam 1000 mg twice daily for his post-traumatic epilepsy. After taking his medication regularly, his facial wounds were noted to have dramatic improvement. In this way, his medication adherence was measured as a function of his healing wounds since a lack of fresh wounds implied a lack of spontaneous seizures and subsequent reinjury. Low-resource medical providers caring for PEH in extra-clinical settings may necessitate using unconventional indicators to assess disease status.

Cutaneous Fungal Infections in Patients Experiencing Homelessness and Treatment in Low-Resource Settings: A Scoping Review.

Patients experiencing homelessness (PEH) suffer from a high burden of cutaneous fungal infections. Preventative treatment is important as such infections can lead to harmful complications such as cellulitis and even osteomyelitis. There are sparse data regarding cutaneous fungal infections of homeless populations and management in low-resource settings. A MEDLINE search was conducted using the key terms "cutaneous," "fungal," "infections," "dermatophytes," and "homeless." The search included case-control, cohort, and randomized controlled trials published in the English language. This scoping review of studies yielded information with regard to practical treatment advice for providers in low-resource settings, including medical, hygiene, prevention, and treatment options for PEH with cutaneous fungal infections, the most common of which were tinea pedis (3-38%) and onychomycosis (1.6-15.5%). Few studies have been conducted on the differences between sheltered and unsheltered homeless patients, which can have treatment implications. Systemic antifungal therapy should be carefully considered for diffuse, refractory, or nail-based cutaneous fungal infections if there is a history of alcohol use disorder or liver disease. While PEH have a high risk of alcohol use disorder, this can make definitive treatment challenging.