Nasal administration of anti-CD3 monoclonal antibody ameliorates disease in a mouse model of Alzheimer's disease.

Emerging evidence suggests that dysregulation of neuroinflammation, particularly that orchestrated by microglia, plays a significant role in the pathogenesis of Alzheimer's disease (AD). Danger signals including dead neurons, dystrophic axons, phosphorylated tau, and amyloid plaques alter the functional phenotype of microglia from a homeostatic (M0) to a neurodegenerative or disease-associated phenotype, which in turn drives neuroinflammation and promotes disease. Thus, therapies that target microglia activation constitute a unique approach for treating AD. Here, we report that nasally administered anti-CD3 monoclonal antibody in the 3xTg AD mouse model reduced microglial activation and improved cognition independent of amyloid beta deposition. In addition, gene expression analysis demonstrated decreased oxidative stress, increased axogenesis and synaptic organization, and metabolic changes in the hippocampus and cortex of nasal anti-CD3 treated animals. The beneficial effect of nasal anti-CD3 was associated with the accumulation of T cells in the brain where they were in close contact with microglial cells. Taken together, our findings identify nasal anti-CD3 as a unique form of immunotherapy to treat Alzheimer's disease independent of amyloid beta targeting.

Accelerated sequential bilateral theta-burst stimulation in major depression: an open trial.

Theta burst stimulation (TBS) is approved and widely used in the treatment of treatment resistant-major depression. More recently, accelerated protocols delivering multiple treatments per day have been shown to be efficacious and potentially enhance outcomes compared to once daily protocols. Meanwhile, bilateral treatment protocols have also been increasingly tested to enhance outcomes. Here, we examined the efficacy and safety of accelerated bilateral TBS in major depressive disorder (MDD). In this open label pilot study, 25 patients with MDD (60%: women; mean age (SD): 45.24 (12.22)) resistant to at least one antidepressant, received bilateral TBS, consisting of 5 sequential bilateral intermittent TBS (iTBS) (600 pulses) and continuous TBS (cTBS) (600 pulses) treatments delivered to the left and right dorsolateral prefrontal cortex (DLPFC), respectively, daily for 5 days at 120% resting motor threshold. Outcome measures were post-treat treatment changes at day 5 and 2-weeks in Hamilton Depression Rating Scale (HDRS-17) scores and response (≥ 50% reduction from the baseline scores) and remission (≤ 7) rates. There was a significant reduction in HDRS scores at day 5 (p < 0.001) and 2-weeks post treatment (p < 0.001). The response rates increased from 20% at day 5 to 32% at 2-weeks post treatment suggesting delayed clinical effects. However, reduction in symptom scores between two post treatment endpoints was non-significant. 60% of patients could not tolerate the high intensity stimulation. No major adverse events occurred. Open label uncontrolled study with small sample size. These preliminary findings suggest that accelerated bilateral TBS may be clinically effective and safe for treatment resistant depression. Randomized sham-controlled trials are needed to establish the therapeutic role of accelerated bilateral TBS in depression.Trial registration: ClinicalTrials.gov, NCT10001858.

Ordered Mesoporous Carbon as Adsorbent for the Removal of a Triphenylmethane Dye from Its Aqueous Solutions.

A nanostructured material, ordered mesoporous carbon (OMC), was synthesised in metal- and halide-free form and its use for the sequestration of crystal violet, a hazardous triphenylmethane dye, is reported for the first time. The OMC material is characterised using scanning transmission electron microscopy with energy-dispersive spectroscopy for chemical analysis, by Fourier-transform infrared spectroscopy, and by nitrogen gas physisorption. The ideal conditions for the uptake of crystal violet dye were determined in batch experiments covering the standard parameters: pH, concentration, contact time, and adsorbent dosage. Experimental data are validated by applying Langmuir, Freundlich, Dubinin-Radushkevich, and Temkin isotherms. The thermodynamic parameters, ΔH°, ΔG°, and ΔS°, are calculated and it has been found that the adsorption process is spontaneous and endothermic with increasing disorder. An in-depth analysis of the kinetics of the adsorption process, order of the reaction and corresponding values of the rate constants was performed. The adsorption of crystal violet over OMC has been found to follow pseudo-second-order kinetics through a film diffusion process at all temperatures studied. Continuous flow column operations were performed using fixed bed adsorption. Parameters including percentage saturation of the OMC bed are evaluated. The exhausted column was regenerated through a desorption process and column efficiency was determined.

Deciphering glycomics and neuroproteomic alterations in experimental traumatic brain injury: Comparative analysis of aspirin and clopidogrel treatment.

As populations age, the number of patients sustaining traumatic brain injury (TBI) and concomitantly receiving preinjury antiplatelet therapy such as aspirin (ASA) and clopidogrel (CLOP) is rising. These drugs have been linked with unfavorable clinical outcomes following TBI, where the exact mechanism(s) involved are still unknown. In this novel work, we aimed to identify and compare the altered proteome profile imposed by ASA and CLOP when administered alone or in combination, prior to experimental TBI. Furthermore, we assessed differential glycosylation PTM patterns following experimental controlled cortical impact model of TBI, ASA, CLOP, and ASA + CLOP. Ipsilateral cortical brain tissues were harvested 48 h postinjury and were analyzed using an advanced neuroproteomics LC-MS/MS platform to assess proteomic and glycoproteins alterations. Of interest, differential proteins pertaining to each group (22 in TBI, 41 in TBI + ASA, 44 in TBI + CLOP, and 34 in TBI + ASA + CLOP) were revealed. Advanced bioinformatics/systems biology and clustering analyses were performed to evaluate biological networks and protein interaction maps illustrating molecular pathways involved in the experimental conditions. Results have indicated that proteins involved in neuroprotective cellular pathways were upregulated in the ASA and CLOP groups when given separately. However, ASA + CLOP administration revealed enrichment in biological pathways relevant to inflammation and proinjury mechanisms. Moreover, results showed differential upregulation of glycoproteins levels in the sialylated N-glycans PTMs that can be implicated in pathological changes. Omics data obtained have provided molecular insights of the underlying mechanisms that can be translated into clinical bedside settings.

Glycosylation and other PTMs alterations in neurodegenerative diseases: Current status and future role in neurotrauma.

Traumatic brain injuries (TBIs) present a chief public health threat affecting nations worldwide. As numbers of patients afflicted by TBI are expected to rise, the necessity to increase our understanding of the pathophysiological mechanism(s) as a result of TBI mounts. TBI is known to augment the risk of developing a number of neurodegenerative diseases (NDs) such as Alzheimer's disease (AD) and Parkinson's disease (PD). Hence, it is rational to assume that a common mechanistic ground links the pathophysiology of NDs to that of TBIs. Through this review, we aim to identify the protein-protein interactions, differential proteins expression, and PTMs, mainly glycosylation, that are involved in the pathogenesis of both ND and TBI. OVID and PubMed have been rigorously searched to identify studies that utilized advanced proteomic platforms (MS based) and systems biology tools to unfold the mechanism(s) behind ND in an attempt to unveil the mysterious biological processes that occur postinjury. Various PTMs have been found to be common between TBI and AD, whereas no similarities have been found between TBI and PD. Phosphorylated tau protein, glycosylated amyloid precursor protein, and many other modifications appear to be common in both TBI and AD. PTMs, differential protein profiles, and altered biological pathways appear to have critical roles in ND processes by interfering with their pathological condition in a manner similar to TBI. Advancement in glycoproteomic studies pertaining to ND and TBI is urgently needed in order to develop better diagnostic tools, therapies, and more favorable prognoses.

Holohemispheric Intracranial Subdural Empyema as a Complication of Orbital Cellulitis.

Intracranial subdural empyema is a loculated collection of pus in the subdural space between the dura mater and the arachnoid that can be life-threatening. Here, we present a case of a 22-year-old man hospitalized for management of sepsis due to right orbital cellulitis who experienced sudden-onset right-sided hemiplegia and was found to have a holohemispheric intracranial subdural empyema requiring emergent neurosurgical intervention. Subdural empyemas are commonly caused by maxillofacial infections, including orbital infections. We demonstrate that orbital cellulitis may cause an intracranial subdural empyema that can present with sudden-onset neurological deficits warranting prompt neurosurgical intervention.

Unveiling food safety knowledge and practices among pet owners in Lebanon.

Owning pets offers various potential health benefits; however, it can be associated with gastrointestinal illnesses due to poor food safety knowledge and practices. This study aimed to evaluate the level of food safety knowledge and practices among pet owners in Lebanon, exploring the association between their knowledge/practices and socio-demographic characteristics. The participants included 300 pet owners, representing various genders, ages, educational levels, educational backgrounds, and incomes. They completed a questionnaire of 72 food handling practices and knowledge questions related to preparation, cross-contamination, storage and hygiene. In parallel, 300 non-pet owners with comparable sociodemographic characteristics to pet owners (control group) completed the questionnaire. On average, food safety knowledge scores were 62.1 ± 14.9% and 58.7 ± 15.5% among pet and non-pet owners, respectively, and the difference was significant (p = 0.05). On the other hand, mean food safety practice scores were 41.3 ± 14.8% and 40.4 ± 15.3% among pet and non-pet owners, respectively, and the difference was not significant (p = 0.41). In the food safety knowledge part, non-pet owners who were young, high income, university graduate, and from health-related majors scored significantly (p < 0.05) higher, while among pet-owners, only participants with a university degree and from health-related majors scored significantly (p < 0.05) higher, in terms of knowledge. On the other hand, In the food safety practices part, non-pet owners who were young, high income, and university graduates scored significantly (p < 0.05) higher, while among pet-owners, only young and high-income participants scored significantly (p < 0.05) higher. These results highlight the need for ongoing educational initiatives to improve food safety practices among both pet owners in Lebanon. The study suggests that targeted educational programs should be developed, considering specific socio-demographic characteristics, to enhance overall food safety awareness and practices among the population.

A Large Lambl's Excrescence Causing Embolic Stroke in a Young Patient: A Case Report and Review of Literature.

Lambl's excrescences (LEs) are thin, filiform and hypermobile strands that develop at the valvular coaptation sites of the heart. Since first described in 1856 by Vilém Dusan Lambl, there has been an increasing number of reports of central and peripheral emboli arising from cardiac LEs. LEs have been linked to ischemic strokes irrespective of age and comorbidities. We report one of the youngest reported cases in literature of an embolic stroke in a 25-year-old woman caused by a LE. A comprehensive workup was performed that revealed a large aortic valve LE. The patient was discharged on dual anti-platelet therapy with outpatient cardiology follow-up for surveillance echocardiograms. We then surveyed the literature and reviewed case reports and observational studies of LEs linked to systemic emboli. We found that most LEs are present on left-sided high-pressure valves especially the ventricular aspect of the aortic valves and that most reported cases of cerebral embolism had aortic valve LEs. The management of cardioembolic stroke secondary to LEs remains unclear. LEs have not been identified as a definite etiology of cardioembolic strokes warranting the need for large-scale studies to help guide the management of cardiac LEs in the setting of ischemic stroke.

HPLC-ESI/MS-MS metabolic profiling of white pitaya fruit and cytotoxic potential against cervical cancer: Comparative studies, synergistic effects, and molecular mechanistic approaches.

Natural approach became a high demand for the prevention and treatment of such diseases for their proven safety and efficacy. This study is aimed to perform comparative phytochemical analysis of white pitaya (Hylocereus undatus) peel, pulp and seed extracts via determination of total flavonoid content, phenolic content, and antioxidant capacity, coupled with HPLC-ESI/MS-MS analysis. Further, we evaluated the synergistic cytotoxic potential with Cisplatin against cervical cancer cells with investigation of underlying mechanism. The highest content of phenolics and antioxidants were found in both seed and peel extracts. The HPLC-ESI/MS-MS revealed identification of flavonoids, phenolic acids, anthocyanin glycosides, lignans, stilbenes, and coumarins. The cytotoxicity effects were evaluated by MTT assay against prostate, breast and cervical (HeLa) and Vero cell lines. The seed and peel extracts showed remarkable cytotoxic effect against all tested cell lines. Moreover, the selectivity index confirmed high selectivity of pitaya extracts to cancer cells and safety on normal cells. The combined therapy with Cisplatin effectively enhanced its efficacy and optimized the treatment outcomes, through the apoptotic ability of pitaya extracts in HeLa cells, as evaluated by flow cytometry. Besides, RT-PCR and western blotting analysis showed downregulation of Bcl-2 and overexpression of P53, BAX among HeLa cells treated with pitaya extracts, which eventually activated apoptosis process. Thus, pitaya extract could be used as adjuvant therapy with cisplatin for treatment of cervical cancer. Furthermore, in-vivo extensive studies on the seed and peel extracts, and their compounds are recommended to gain more clarification about the required dose, and side effects.

Targeted Photodynamic Therapy using a Vectorized Photosensitizer coupled to Folic Acid Analog induces Ovarian Tumor Cell Death and inhibits IL-6-mediated Inflammation.

Ovarian cancer (OC) is one of the most lethal cancers among women. Frequent recurrence in the peritoneum due to the presence of microscopic tumor residues justifies the development of new therapies. Indeed, our main objective is to develop a targeted photodynamic therapy (PDT) treatment of peritoneal carcinomatosis from OC to improve the life expectancy of cancer patients. Herein, we propose a targeted-PDT using a vectorized photosensitizer (PS) coupled with a newly folic acid analog (FAA), named PSFAA, in order to target folate receptor alpha (FRα) overexpressed on peritoneal metastasis. This PSFAA was the result of the coupling of pyropheophorbide-a (Pyro-a), as the PS, to a newly synthesized FAA via a polyethylene glycol (PEG) spacer. The selectivity and the PDT efficacy of PSFAA was evaluated on two human OC cell lines overexpressing FRα compared to fibrosarcoma cells underexpressing FRα. Final PSFAA, including the synthesis of a newly FAA and its conjugation to Pyro-a, was obtained after 10 synthesis steps, with an overall yield of 19%. Photophysical properties of PSFAA in EtOH were performed and showed similarity with those of free Pyro-a, such as the fluorescence and singlet oxygen quantum yields (Φf = 0.39 and ΦΔ = 0.53 for free Pyro-a, and Φf = 0.26 and ΦΔ = 0.41 for PSFAA). Any toxicity of PSFAA was noticed. After light illumination, a dose-dependent effect on PS concentration and light dose was shown. Furthermore, a PDT efficacy of PSFAA on OC cell secretome was detected inducing a decrease of a pro-inflammatory cytokine secretion (IL-6). This new PSFAA has shown promising biological properties highlighting the selectivity of the therapy opening new perspectives in the treatment of a cancer in a therapeutic impasse.

High-salt diet induces microbiome dysregulation, neuroinflammation and anxiety in the chronic period after mild repetitive closed head injury in adolescent mice.

The associations between human concussions and subsequent sequelae of chronic neuropsychiatric and cardiovascular diseases such as hypertension have been reported; however, little is known about the underlying biological processes. We hypothesized that dietary changes, including a high-salt diet, disrupt the bidirectional gut-brain axis, resulting in worsening neuroinflammation and emergence of cardiovascular and behavioural phenotypes in the chronic period after repetitive closed head injury in adolescent mice. Adolescent mice were subjected to three daily closed head injuries, recovered for 12 weeks and then maintained on a high-salt diet or a normal diet for an additional 12 weeks. Experimental endpoints were haemodynamics, behaviour, microglial gene expression (bulk RNA sequencing), brain inflammation (brain tissue quantitative PCR) and microbiome diversity (16S RNA sequencing). High-salt diet did not affect systemic blood pressure or heart rate in sham or injured mice. High-salt diet increased anxiety-like behaviour in injured mice compared to sham mice fed with high-salt diet and injured mice fed with normal diet. Increased anxiety in injured mice that received a high-salt diet was associated with microgliosis and a proinflammatory microglial transcriptomic signature, including upregulation in interferon-gamma, interferon-beta and oxidative stress-related pathways. Accordingly, we found upregulation of tumour necrosis factor-alpha and interferon-gamma mRNA in the brain tissue of high salt diet-fed injured mice. High-salt diet had a larger effect on the gut microbiome composition than repetitive closed head injury. Increases in gut microbes in the families Lachnospiraceae, Erysipelotrichaceae and Clostridiaceae were positively correlated with anxiety-like behaviours. In contrast, Muribaculaceae, Acholeplasmataceae and Lactobacillaceae were negatively correlated with anxiety in injured mice that received a high-salt diet, a time-dependent effect. The findings suggest that high-salt diet, administered after a recovery period, may affect neurologic outcomes following mild repetitive head injury, including the development of anxiety. This effect was linked to microbiome dysregulation and an exacerbation of microglial inflammation, which may be physiological targets to prevent behavioural sequelae in the chronic period after mild repetitive head injury. The data suggest an important contribution of diet in determining long-term outcomes after mild repetitive head injury.

A 44-Year-Old Male With Cerebral Venous Sinus Thrombosis.

Cerebral venous sinus thrombosis (CVST) is a rare condition that can result in severe neurological complications when left untreated. Disease pathology results from thrombus development within the superficial cortical veins or the dural sinuses. Thrombosis impedes cerebral drainage leading to venous congestion and consequent increase in cerebral pressure, parenchymal damage, and blood-brain barrier disruption. Headache is the most common presenting symptom; other symptoms include focal neurological signs, seizures, papilledema, and altered sensorium. Diagnosis is typically made with visualization of obstructed flow in the cerebral venous system using one of three imaging modalities: computed tomography-venography (CTV), magnetic resonance imaging with venography (MRV), and diagnostic cerebral angiography. First-line therapy for CVST is anticoagulation, and the prognosis is generally favorable with early detection and prompt treatment. In this case report, we discuss a singular case of a patient presenting with loss of consciousness who was found to have CVST and treated with anticoagulation therapy in the setting of an intraparenchymal hemorrhage.

Hemophagocytic Lymphohistiocytosis Caused by a Severe Epstein-Barr Virus Infection in a Young Patient Presenting With Hiccups.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome characterized by a pathologic immune response in the setting of infection, malignancy, acute illness, or any immunological stimulus. Infection is the most common etiology of HLH. HLH involves aberrant activation of lymphocytes and macrophages with resultant hypercytokinemia due to an inappropriately stimulated and ineffective immune response. Here, we present the case of a previously healthy 19-year-old male presenting with hiccups and scleral icterus, who was found to have HLH due to a severe Epstein-Barr virus infection. Despite a morphologically normal bone marrow biopsy, the patient met the diagnostic criteria for HLH, including a low natural killer cell count and elevated soluble interleukin-2 receptor. Notably, ferritin was severely elevated at 85,810 ng/mL. The patient was treated with an induction course of dexamethasone intravenously for eight weeks. Since HLH can progress into multi-organ failure, timely diagnosis and prompt initiation of treatment are critical. Novel disease-modifying therapies and further clinical trials are warranted to treat this potentially fatal immunological disease with multisystem ramifications.

Incidental Moyamoya Disease in an Elderly Patient Presenting With Acute Ischemic Pontine Stroke.

Moyamoya disease (MMD) is a rare occlusive cerebrovascular disease that is characterized by progressive stenosis of the terminal portion of the internal carotid artery and its main branches with compensatory development of dilated and fragile collateral vasculature at the base of the brain. MMD has a bimodal age distribution commonly affecting children and adults, whereas onset in the elderly population is a rare occurrence. Here, we present a case of a 78-year-old patient of Indonesian descent who was incidentally found to have moyamoya arteriopathy after presenting with acute ischemic stroke in the left pons. The patient underwent diagnostic cerebral angiogram that showed right middle cerebral artery stenosis with pathognomonic collateral moyamoya vessels. The patient was discharged on antiplatelet therapy. We report a rare case of an elderly patient with MMD. The role of medical or surgical management in asymptomatic MMD in elderly patients remains largely unknown.

Atypical Seropositive Striated Muscle Antibody Myasthenia Gravis Presentation With Metastatic B1 Thymoma: A Rare Case.

The association between myasthenia gravis (MG) and thymomas is well-documented. Thymomas are rare epithelial cell tumors that arise from the thymus gland and occur in the mediastinum. Myasthenia gravis is a neuromuscular disorder that causes skeletal muscle weakness due to the presence of anti-acetylcholinesterase antibodies. Roughly 60% of thymomas are associated with MG, while only 10% of MG patients have thymomas. We present an atypical presentation of myasthenia gravis with an associated unusual metastatic thymoma. This case is of a young, previously healthy 26-year-old male with no previous medical history who presented with non-specific symptoms of fatigue, diarrhea, abdominal pain, back pain, blurry vision, and unintended weight loss. He underwent treatment with intravenous immunoglobulins (IVIG), had two surgical resections of the thymoma, and ultimately received radiotherapy. Based on our experience with this case, diagnosing myasthenia gravis by testing for specific muscle antibodies for patients with ptosis in the setting of non-specific complaints, including fatigue, vomiting, diarrhea, and abdominal or back pain, should be considered. Routine imaging should follow with a chest computed tomography to screen for thymomas if the specific anti-titin and anti-ryanodine receptor (anti-RyR) muscle antibodies are positive and myasthenia gravis is suspected. If a thymoma is confirmed, it is best to confirm; and mass characterizes with chest magnetic resonance imaging. A treatment approach of IVIG followed by surgical resection and possible debulking if the lesion is deemed metastatic could also be considered thereafter, especially in young patients with few comorbidities. Treatment with Pyridostigmine 30 mg twice daily for 25 days post-surgically and radiation for treatment of any remaining unresectable tumor should also be considered.

Elucidating the neuroimmunology of traumatic brain injury: methodological approaches to unravel intercellular communication and function.

The neuroimmunology of traumatic brain injury (TBI) has recently gained recognition as a crucial element in the secondary pathophysiological consequences that occur following neurotrauma. Both immune cells residing within the central nervous system (CNS) and those migrating from the periphery play significant roles in the development of secondary brain injury. However, the precise mechanisms governing communication between innate and adaptive immune cells remain incompletely understood, partly due to a limited utilization of relevant experimental models and techniques. Therefore, in this discussion, we outline current methodologies that can aid in the exploration of TBI neuroimmunology, with a particular emphasis on the interactions between resident neuroglial cells and recruited lymphocytes. These techniques encompass adoptive cell transfer, intra-CNS injection(s), selective cellular depletion, genetic manipulation, molecular neuroimaging, as well as in vitro co-culture systems and the utilization of organoid models. By incorporating key elements of both innate and adaptive immunity, these methods facilitate the examination of clinically relevant interactions. In addition to these preclinical approaches, we also detail an emerging avenue of research that seeks to leverage human biofluids. This approach enables the investigation of how resident and infiltrating immune cells modulate neuroglial responses after TBI. Considering the growing significance of neuroinflammation in TBI, the introduction and application of advanced methodologies will be pivotal in advancing translational research in this field.

Vγ1 and Vγ4 gamma-delta T cells play opposing roles in the immunopathology of traumatic brain injury in males.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality. The innate and adaptive immune responses play an important role in the pathogenesis of TBI. Gamma-delta (γδ) T cells have been shown to affect brain immunopathology in multiple different conditions, however, their role in acute and chronic TBI is largely unknown. Here, we show that γδ T cells affect the pathophysiology of TBI as early as one day and up to one year following injury in a mouse model. TCRδ-/- mice are characterized by reduced inflammation in acute TBI and improved neurocognitive functions in chronic TBI. We find that the Vγ1 and Vγ4 γδ T cell subsets play opposing roles in TBI. Vγ4 γδ T cells infiltrate the brain and secrete IFN-γ and IL-17 that activate microglia and induce neuroinflammation. Vγ1 γδ T cells, however, secrete TGF-ß that maintains microglial homeostasis and dampens TBI upon infiltrating the brain. These findings provide new insights on the role of different γδ T cell subsets after brain injury and lay down the principles for the development of targeted γδ T-cell-based therapy for TBI.

Tuberculosis of talus: A case report.

INTRODUCTION: Osteoarticular tuberculosis represents 1 to 3% of all tuberculosis cases, the tuberculosis of the talus is a very rare form of osteoarticular tuberculosis. Its clinical and radiological features are not specific. In this study, we report a case of ankle tuberculosis involving the talus in a 5-year-old girl. CASE REPORT: A 5 years old girl, was admitted for pain, swelling, and functional impairment of the left ankle, on the clinical examination, the patient manifested a painful oedematous ankle. The biological examination revealed a slight inflammatory syndrome, The X-ray of the ankle showed a lytic image of the posterior part of the talus with a cortical involvement. The biopsy revealed an epithelioid cell granuloma without any caseous necrosis. The medical management consisted of anti-tuberculosis multi-drug. DISCUSSION: The tuberculosis of the talus is a very rare form of osteoarticular tuberculosis. In this study, we report a rare case of this localization of a 5-year-old girl. The non-specificity of symptoms is the main difficulty that causes a delay in diagnosis. Standard radiology, MRI, and biology were non-contributory. Bone biopsy and anatomopathological study led to the diagnosis of tuberculosis of the talus. The main aims of the surgical treatment are to take some sample for histological study, and to curette the diseased part in the bone followed by 6 to 9 months of anti-tuberculosis chemotherapy. CONCLUSION: Tuberculosis of the talus is extremely rare, it deserves special attention especially in endemic areas.

Herb-drug interactions and toxicity: Underscoring potential mechanisms and forecasting clinically relevant interactions induced by common phytoconstituents via data mining and computational approaches.

Herbals in the form of medicine are employed extensively around the world. Herbal and conventional medicine combination is a potentially dangerous practice mainly in comorbid, hepato insufficient and frail patients leading to perilous herb-drug interactions (HDI) and toxicity. This study features potential HDI of 15 globally famous plant species through data mining and computational methods. Several plant species were found to mimic warfarin. Phytochemicals from M. charantia induced hypoglycemica. M. chamomila and G. biloba possessed anticoagulant activities. S. hispanica reduces postprandial glycemia. R. officinalis has been reported to inhibit the efflux of anticancer substrates while A. sativum can boost the clearance of anticancer agents. P. ginseng can alter blood coagulation. A cross link of the biological and in silico data revealed that a plethora of herbal metabolites such as ursolic and rosmarinic acid among others are possible/probable inhibitors of specific CYP450 enzymes. Consequently, plant species/metabolites with a given pharmacological property/metabolizing enzyme should not be mixed with drugs having the same pharmacological property/metabolizing enzyme. Even if combined with drugs, herbal medicines must be used at low doses for a short period of time and under the supervision of a healthcare professional to avoid potential adverse and toxic effects.

Myeloid cell subsets that express latency-associated peptide promote cancer growth by modulating T cells.

Myeloid suppressor cells promote tumor growth by a variety of mechanisms which are not fully characterized. We identified myeloid cells (MCs) expressing the latency-associated peptide (LAP) of TGF-ß on their surface and LAPHi MCs that stimulate Foxp3+ Tregs while inhibiting effector T cell proliferation and function. Blocking TGF-ß inhibits the tolerogenic ability of LAPHi MCs. Furthermore, adoptive transfer of LAPHi MCs promotes Treg accumulation and tumor growth in vivo. Conversely, anti-LAP antibody, which reduces LAPHi MCs, slows cancer progression. Single-cell RNA-Seq analysis on tumor-derived immune cells revealed LAPHi dominated cell subsets with distinct immunosuppressive signatures, including those with high levels of MHCII and PD-L1 genes. Analogous to mice, LAP is expressed on myeloid suppressor cells in humans, and these cells are increased in glioma patients. Thus, our results identify a previously unknown function by which LAPHi MCs promote tumor growth and offer therapeutic intervention to target these cells in cancer.