Transient ischemic attack and minor stroke as "surgeons affairs": a narrative review.

OBJECTIVE: The scope of this paper is to review the subtypes of transient ischemic attack (TIA) and minor stroke (mS) in which a surgical treatment is needed, discussing the importance and the timing of a multidisciplinary approach, in order to achieve an optimized management and prevent major strokes or other critical complications. MATERIALS AND METHODS: The keywords "transient ischemic attack," "minor stroke," "surgical treatment," "vascular surgery," "heart surgery," "neurosurgery," and "multidisciplinary" were searched using MEDLINE, EMBASE, and Scopus. Relevant search results were discussed by the authors for references inclusion. RESULTS: Notwithstanding that best medical therapy is usually the first choice for the most part of cases, there are specific but recurrent etiologies that must be properly recognized because of a potential surgical approach, even in urgency. In fact, symptomatic carotid stenosis, or particular cases of hemodynamic cerebrovascular events, should be promptly referred to vascular surgeon, since increasing evidences highlighted a benefit from an early artery revascularization. In addition, beyond arrhythmic causes, cardioembolic events due to bacterial endocarditis and atrial myxoma should be quickly diagnosed, possibly in emergency department, because they are a presumptive urgency for heart surgery. In addition to the above-mentioned conditions, in patients suffering from vertebrobasilar TIA or mS, clinicians should keep in mind the Bow Hunter disease, because surgical artery decompression can represent the only suitable treatment in selected cases. CONCLUSIONS: TIA and mS require a multidisciplinary in order to discuss therapeutic options, comparing risks and benefits and determining the best timing for an optimized management.

Hyaluronic acid in vulvar and vaginal administration: evidence from a literature systematic review.

Vulvovaginal pathology impairs the quality of life of both women in menopause and those who are not. Different therapies have been proposed, mainly related to estrogen therapy in postmenopausal women. However, some contraindications limit its use, and different moisturizers or lubricants have been tested. Hyaluronic acid is a promising and widely used vaginal medical treatment with a moisturizing action and appears to provide a solution. For this reason, we performed a systematic review of the literature. We searched for original articles without date restriction until 30 April 2020. We included all clinical trials which administered local hyaluronic acid in the vulva or vagina. Only English studies and those performed in humans were eligible. Seventeen original studies were included in the review (from randomized controlled trials to longitudinal studies). Hyaluronic acid was generally found to be effective in improving vulvovaginal symptoms (dyspareunia, itching, burning, dryness) and signs (bleeding, atrophy, vaginal pH). In conclusion, hyaluronic acid has the properties to be an efficient moisturizer for women suffering from vulvovaginal atrophy who have contraindications for estrogen therapy and for vulvovaginal signs and symptoms affecting sexual well-being. However, a well-designed randomized controlled trial is needed in order to clarify its efficacy and safety profile.

Polycystic ovary syndrome management: a review of the possible amazing role of berberine.

PURPOSE: The therapy of polycystic ovary syndrome (PCOS) is based on synthetic hormones associated with lifestyle changes, but these therapies cannot be taken continuously, especially by women who would like to become pregnant. Thus, nutraceutical compounds were investigated as possible agents for treatment of PCOS. Berberine is shown to be effective against insulin resistance and obesity, particularly against visceral adipose tissue (VAT). Because of these properties, researchers theorized that berberine could be effective in PCOS treatment. METHODS: The aim of this narrative review was to assess the state of the art about the use of berberine in PCOS management. RESULTS: This review included 5 eligible studies. Despite the number of studies considered being low, the number of women studied is high (1078) and the results are interesting. Two authors find out that berberine induced a redistribution of adipose tissue, reducing VAT in the absence of weight loss and improved insulin sensitivity, quite like metformin. One author demonstrated that berberine improved the lipid pattern. Moreover, three authors demonstrated that berberine improved insulin resistance in theca cells with an improvement of the ovulation rate per cycle, so berberine is also effective on fertility and live birth rates. CONCLUSIONS: Finally, berberine is safe to use in premenopausal women who want to get pregnant and showed few side effects in all the cited studies. In conclusion, the use of berberine for PCOS is safe and promising, even if more studies are needed to create a consensus about the dosage of berberine useful for long-term therapy.

Comparison between Bioimpedance Analysis and Dual-Energy X-ray Absorptiometry in assessment of body composition in a cohort of elderly patients aged 65-90 years.

We compare bioimpedance analysis (BIA) with dual-energy X-ray absorptiometry (DXA) in the assessment of free fat mass (FFM), fat mass (FM) and percentage of body fat under different conditions in relation to age categories, hydration parameters, body mass index (BMI) and sarcopenia. A cross-sectional analysis of body composition was estimated by BIA and DXA in 379 hospitalized elderly patients. In addition, estimates of FFM, FM and percentage of body fat were investigated across different conditions. Paired t-tests, Bland-Altman plot and intraclass correlation coefficient analysis were used to compare methods. Data showed an underestimation of means (BIA versus DXA) of FFM (women: 0,97 kg, p<0,01; men: 1,99 kg; p<0,01), and an overestimation of both the FM (women: +1,11 kg; p<0,01; men: +1,67 kg; p<0,01) and percentage of body fat (women: +2,07 %, p<0,01; men: +2,82 %, p<0,01). BIA underestimated FFM and overestimated FM and percentage of body fat in patients from the age group of 75 to 85 years, in patients with a total body water content <60%, in underweight and normal weight patients and in patients with sarcopenia (p<0,01). The intraclass coefficient results were indicative of poor reproducibility between BIA and DXA for FFM (women: +0,197; men: +0,250) and FM (women: +0,141; men +0,144). BIA is a good alternative for estimation of FFM and FM only in overweight or obese patients or in patients with good hydration status. BIA, on the other hand, is not an accurate method for assessing FFM in sarcopenic patients.

Apheresis treatment of cryoglobulinemic vasculitis: A multicentre cohort study of 159 patients.

OBJECTIVE: To assess the effectiveness of apheresis therapy (AT) in treating the clinical manifestations of patients with complicated cryoglobulinemic vasculitis (CV). METHODS: A retrospective cohort study of 159 CV patients attending 22 Italian Centers who underwent at least one AT session between 2005 and 2015. The response to AT was evaluated on the basis of a defined grading system. RESULTS: Peripheral neuropathy was the most frequent clinical condition leading to AT. Therapeutic plasma exchange was used in 70.4% of cases. The outcome of AT was rated very good in 19 cases, good in 64, partial/transient in 40, and absent/not assessable in 36. Life-threatening CV-related emergencies and renal impairment independently correlated with failure to respond to AT. The independent variables associated with an increased risk of death were age at the time of the first AT session, multi-organ life-threatening CV, the presence of renal impairment and failure to respond to AT. The time-dependent probability of surviving until CV-related death in the second year was 84%, with an AHR in patients with absent/not assessable response to AT of 11.25. CONCLUSION: In this study AT is confirmed to be a safe procedure in patients with CV. Early AT should be considered in patients with severe CV, especially in cases with impending renal involvement, in order to prevent irreversible kidney damage. Although its efficacy in patients with multi-organ failure is limited, AT is the only treatment that can rapidly remove circulating cryoglobulins, and should be considered an emergency treatment.

The increasing burden and complexity of multi-morbidity and polypharmacy in geriatric HIV patients: a cross sectional study of people aged 65 - 74 years and more than 75 years.

BACKGROUND: Geriatric Patients Living with HIV/AIDS (GEPPO) is a new prospective observational multicentre cohort consisting of all the HIV-positive geriatric patients being treated at 10 clinics in Italy, and HIV-negative controls attending a single geriatric clinic. The aim of this analysis of the GEPPO cohort was to compare prevalence and risk factors of individual non-communicable diseases (NCD), multi-morbidity (MM) and polypharmacy (PP) amongst HIV positive and HIV negative controls at enrolment into the GEPPO cohort. METHODS: This cross-sectional study was conducted between June 2015 and May 2016. The duration of HIV infection was subdivided into three intervals: < 10, 10-20 and > 20 years. The NCD diagnoses were based on guidelines defined criteria, including cardiovascular disease, hypertension, type 2 diabetes, chronic kidney disease, dyslipidaemia, chronic obstructive pulmonary disease. MM was classified as the presence of two or more co-morbidities. The medications prescribed for the treatment of comorbidities were collected in both HIV positive and HIV negative group from patient files and were categorized using the Anatomical Therapeutic Chemical (ATC) classification. PP was defined as the presence of five or more drug components other than anti-retroviral agents. RESULTS: The study involved a total of 1573 patient: 1258 HIV positive and 315 HIV negative). The prevalence of individual comorbidities was similar in the two groups with the exception of dyslipidaemia, which was more frequent in the HIV-positive patients (p <  0.01). When the HIV-positive group was stratified based on the duration of HIV infection, most of the co-morbidities were significantly more frequent than in control patients, except for hypertension and cardiovascular disease, while COPD was more prevalent in the control group. MM and PP were both more prevalent in the HIV-positive group, respectively 64% and 37%. CONCLUSIONS: MM and PP burden in geriatric HIV positive patients are related to longer duration of HIV-infection rather than older age per se.

Environmental life cycle assessment of Italian mozzarella cheese: Hotspots and improvement opportunities.

The present study investigated a cradle-to-grave life cycle assessment to estimate the environmental impacts associated with Italian mozzarella cheese consumption. The differences between mozzarella produced from raw milk and mozzarella produced from curd were studied, and differences in manufacturing processes have been emphasized in order to provide guidance for targeted improvements at this phase. Specifically, the third-largest Italian mozzarella producer was surveyed to collect site-specific manufacturing data. The Ecoinvent v3.2 database was used for secondary data, whereas SimaPro 8.1 was the modeling software. The inventory included inputs from farm activities to end of life disposal of wasted mozzarella and packaging. Additionally, plant-specific information was used to assign major inputs, such as electricity, natural gas, packaging, and chemicals to specific products; however, where disaggregated information was not provided, milk solids allocation was applied. Notably, loss of milk solids was accounted during the manufacture, moreover mozzarella waste and transport were considered during distribution, retail, and consumption phases. Feed production and animal emissions were the main drivers of raw milk production. Electricity and natural gas usage, packaging (cardboard and plastic), transport, wastewater treatment, and refrigerant loss affected the emissions from a farm gate-to-dairy plant gate perspective. Post-dairy plant gate effects were mainly determined by electricity usage for storage of mozzarella, transport of mozzarella, and waste treatment. The average emissions were 6.66 kg of CO2 equivalents and 45.1 MJ of cumulative energy demand/kg of consumed mozzarella produced directly from raw milk, whereas mozzarella from purchased curd had larger emissions than mozzarella from raw milk due to added transport of curd from specialty manufacturing plants, as well as electricity usage from additional processes at the mozzarella plant that are required to process the curd into mozzarella. Normalization points to ecotoxicity as the impact category most significantly influenced by mozzarella consumption. From a farm gate-to-grave perspective, ecotoxicity and freshwater and marine eutrophication are the first and second largest contributors of mozzarella consumption to average European effects, respectively. To increase environmental sustainability, an improvement of efficiency for energy and packaging usage and transport activities is recommended in the post-farm gate mozzarella supply chain.

Osteopontin neutralisation abrogates the liver progenitor cell response and fibrogenesis in mice.

BACKGROUND: Chronic liver injury triggers a progenitor cell repair response, and liver fibrosis occurs when repair becomes deregulated. Previously, we reported that reactivation of the hedgehog pathway promotes fibrogenic liver repair. Osteopontin (OPN) is a hedgehog-target, and a cytokine that is highly upregulated in fibrotic tissues, and regulates stem-cell fate. Thus, we hypothesised that OPN may modulate liver progenitor cell response, and thereby, modulate fibrotic outcomes. We further evaluated the impact of OPN-neutralisation on murine liver fibrosis. METHODS: Liver progenitors (603B and bipotential mouse oval liver) were treated with OPN-neutralising aptamers in the presence or absence of transforming growth factor (TGF)-ß, to determine if (and how) OPN modulates liver progenitor function. Effects of OPN-neutralisation (using OPN-aptamers or OPN-neutralising antibodies) on liver progenitor cell response and fibrogenesis were assessed in three models of liver fibrosis (carbon tetrachloride, methionine-choline deficient diet, 3,5,-diethoxycarbonyl-1,4-dihydrocollidine diet) by quantitative real time (qRT) PCR, Sirius-Red staining, hydroxyproline assay, and semiquantitative double-immunohistochemistry. Finally, OPN expression and liver progenitor response were corroborated in liver tissues obtained from patients with chronic liver disease. RESULTS: OPN is overexpressed by liver progenitors in humans and mice. In cultured progenitors, OPN enhances viability and wound healing by modulating TGF-ß signalling. In vivo, OPN-neutralisation attenuates the liver progenitor cell response, reverses epithelial-mesenchymal-transition in Sox9+ cells, and abrogates liver fibrogenesis. CONCLUSIONS: OPN upregulation during liver injury is a conserved repair response, and influences liver progenitor cell function. OPN-neutralisation abrogates the liver progenitor cell response and fibrogenesis in mouse models of liver fibrosis.

Ageing with HIV: a multidisciplinary review.

INTRODUCTION: After the introduction of highly active antiretroviral treatment, the course of HIV infection turned into a chronic disease and most of HIV-positive patients will soon be over 50 years old. MATERIAL AND METHODS: This paper reviews the multiple aspects that physicians have to face while taking care of HIV-positive ageing patients including the definitions of frailty and the prevalence and risk factors of concomitant diseases. From a therapeutic point of view pharmacokinetic changes and antiretroviral-specific toxicities associated with ageing are discussed; finally therapeutic approaches to frailty are reviewed both in HIV-positive and negative patients. CONCLUSION AND DISCUSSION: We conclude by suggesting that the combined use of drugs with the least toxicity potential and the promotion of healthy behaviours (including appropriate nutrition and exercise) might be the best practice for ageing HIV-positive subjects.

Parasympathetic vasoactive intestinal peptide (VIP): a likely contributor to clozapine-induced sialorrhoea.

OBJECTIVE: The parasympathetic transmitter vasoactive intestinal peptide (VIP) increases salivary gland blood flow and evokes protein secretion and, in some species, such as rats, a small fluid secretion. It interacts synergistically with muscarinics for protein and fluid output. Human salivary acini are supplied with VIP-containing nerves. We hypothesise that VIP and clozapine, acting together, evoke a volume of saliva greater than the sum of those induced by each drug given separately. It was further considered whether, in the current test situation, circulatory events influenced the magnitude of the secretory response. MATERIAL AND METHODS: Saliva from parotid glands deprived of their autonomic innervation, and saliva and blood from innervated submandibular glands were collected in adrenoceptor antagonist-pretreated pentobarbitone-anaesthetised rats. Initially, the individual and then the combined effects of intravenous doses of VIP and clozapine were established. RESULTS: The submandibular volume response to the combination was 2-3 times higher, while blood pressure and glandular blood flow did not differ from those to VIP alone. The synergism occurred independent of nerves as shown in denervated parotid glands. CONCLUSIONS: From the current preclinical data, we speculate that VIP of parasympathetic origin, by its synergistic interaction with clozapine, may contribute to the clozapine (muscarinic M1-receptor)-induced sialorrhoea in schizophrenics.

The antipsychotic amisulpride: ultrastructural evidence of its secretory activity in salivary glands.

OBJECTIVE: Amisulpride is reported to inhibit clozapine-induced sialorrhea. Preclinically, clozapine evokes muscarinic-M1-type-mediated secretion that, however, amisulpride does not reduce. Instead, amisulpride, without causing any overt secretion per se, enhances both nerve- and autonomimetic-evoked salivation by unknown mechanism(s). Hypothesizing that amisulpride prepares the gland for secretion, we looked for ultrastructural events indicating secretory activity in intercellular canaliculi of serous/seromucous cells, that is, density increase in protrusions (reflecting anchored granules) and in microbuds (reflecting recycling membranes and/or vesicle secretion) and decrease in microvilli (reflecting the cytoskeletal re-arrangement related to exocytosis). MATERIAL AND METHODS: Rat parotid and submandibular glands were exposed to amisulpride in vivo or in vitro. Glands were processed for transmission electron and scanning electron microscopy and then morphometrically assessed. RESULTS: Cells were packed with secretory granules. The density of protrusions increased in both glands, whereas significant and parallel changes in microvilli and microbuds occurred only in parotid glands, and in vitro. CONCLUSIONS: Amisulpride induced ultrastructural signs of secretory activity but to varying extent; in submandibular glands, in contrast to parotid glands, changes were not brought beyond the granular anchoring stage. Amisulpride may provide an overall readiness for secretion that will result in augmented responses to agonists, a phenomenon of potential interest in dry-mouth treatment.

Peroneal mononeuropathy and polyneuropathy in adolescents with Anorexia Nervosa: a case report and literature review.

Peroneal neuropathy and polyneuropathy are displayed with a variable percentage in subjects affected by eating disorders and in particular by anorexia nervosa. Actually, little is known on features of these complications during the paediatric age. We describe the case of a female adolescent with right peroneal palsy and subclinical polyneuropathy associated with anorexia nervosa (AN). We review previous research about peroneal mononeuropathy and polyneuropathy associated with AN, and we develop a diagnostic and therapeutic protocol to help clinicians recognize and treat these disorders.

Assessment of the diagnostic utility of the electroencephalogram in pediatric emergencies.

INTRODUCTION: We analyze the diagnostic utility of urgent EEG (electroencephalogram) performed in children under 16 years of age in our center. MATERIAL AND METHODS: Descriptive, retrospective, observational study of consecutive patients from 0 to 16 years of age, who underwent an urgent EEG for any reason, from January to December 2022. RESULTS: Of the 388 patients, 70 were children: 37 (52.85%) women, and 33 (47.14%) men. Average age: 6.27 ± 4.809. Of the 70 patients, 6 (8.57%) had previous epilepsy. Reasons for consultation: 17 febrile seizures, 10 first focal seizures, 10 first TCG seizures, 6 paroxysmal episodes, 6 absences, 3 myoclonus of extremities, 3 syncope, 2 SE, 2 visual alterations, 2 low level of consciousness, 2 cyanosis, 2 suspected meningitis or encephalitis, 1 choking, 1 atypical headache, 1 chorea, 1 presyncope, 1 language delay. Of the 70 patients, 47 had a normal EEG (67.14%). Of the 47 patients with a normal EEG, 10 were diagnosed with epilepsy, and 3 of them began receiving antiepileptic treatment upon discharge. None of the patients with suspected syncope or paroxysmal disorder (17 patients, 24.28%) had EEG abnormalities. Of the 17 patients with atypical febrile seizures, 3 had EEG abnormalities. CONCLUSIONS: A third of the EEG records performed in the Emergency Department showed alterations, probably due to the time taken. Almost half of the patients with suspected epilepsy or EE showed EEG abnormalities, which confirmed the diagnosis in these cases and encouraged the clinician to start drug treatment. No case with a high suspicion of epilepsy was dismissed due to the normality of the EEG recording in our series. No patient diagnosed with syncope or paroxysmal disorder had EEG abnormalities. Nearly a quarter of patients with atypical febrile seizures showed EEG abnormalities. We barely register cases of status epilepticus, probably due to the degree of complexity of our center.

HER2 gene copy number status may influence clinical efficacy to anti-EGFR monoclonal antibodies in metastatic colorectal cancer patients.

BACKGROUND: In metastatic colorectal cancer (mCRC), KRAS is the only validated biomarker used to select patients for administration of epidermal growth factor receptor (EGFR)-targeted therapies. To identify additional predictive markers, we investigated the importance of HER2, the primary EGFR dimerisation partner, in this particular disease. METHODS: We evaluated the HER2 gene status by fluorescence in situ hybridisation (FISH) in 170 KRAS wild-type mCRC patients treated with cetuximab or panitumumab. RESULTS: Depending on HER2 gene copy number status, patients showed three distinct cytogenetic profiles: 4% of patients had HER2 gene amplification (R:HER2/CEP17 ≥ 2) in all neoplastic cells (HER2-all-A), 61% of patients had HER2 gain due to polysomy or to gene amplification in minor clones (HER2-FISH+*), and 35% of patients had no or slight HER2 gain (HER2-FISH-). These subgroups were significantly correlated with different clinical behaviours, in terms of response rate (RR; P=0.0006), progression-free survival (PFS; P<0.0001) and overall survival (OS; P<0.0001). Patients with HER2-all-A profile experienced the worst outcome, patients with HER2-FISH- profile showed an intermediate behaviour and patients with HER2-FISH+* profile were related to the highest survival probability (median PFS in months: 2.5 vs 3.9 vs 7.6, respectively; median OS in months: 4.2 vs 9.7 vs 13, respectively). CONCLUSION: HER2 gene copy number status may influence the clinical response to anti-EGFR-targeted therapy in mCRC patients.

Synovial fluid levels of bradykinin correlate with biochemical markers for cartilage degradation and inflammation in knee osteoarthritis.

OBJECTIVE: To determine the content of bradykinin (BK) and markers of cartilage degradation and inflammation in the synovial fluid (SF) of patients with knee osteoarthritis (OA), and to evaluate correlations with biomarkers or clinical parameters. METHODS: SFs were obtained from 30 patients with knee OA. Levels of basal and generated BK, cartilage oligomeric matrix protein (COMP), interleukin (IL) 1, IL-6, IL-8 and matrix metalloprotease (MMP) 1, MMP-3, MMP-13 and sulfated glycosaminoglycans (GAGs) were measured by enzyme-linked immunosorbent assay (ELISA) or colorimetric assays. RESULTS: The mean concentration of basal BK (in the presence of peptidase and protease inhibitors to avoid degradation and de novo formation of BK) was 422 pg/ml (95% confidence interval, CI, 281-563) whereas that of in vitro generated BK (in the presence of peptidase inhibitors SFs were incubated 60 min at 37°C to measure the potential capability to generate BK) was 3427 pg/ml (2591-4264). The content of MMP-13, IL-1α, and IL-1ß was under assay sensitivity. Basal BK levels positively correlated (Spearman's rank correlation) with GAGs (40 µg/ml, 26-54, r = 0.4834, P = 0.0308) and IL-6 (553 pg/ml, 171-935, r = 0.3946, P = 0.0377) similarly to the generated BK (GAGs, r = 0.4563, P = 0.0431; IL-6, r = 0.5605, P = 0.0019). Statistical analysis of basal BK and biomarkers was significant (P = 0.0483). When applying a stepwise logistic regression analysis considering biomarkers together with clinical parameters, results indicated that K/L radiographic OA grade and COMP improved the model (P = 0.0032). CONCLUSION: The presence of BK in the knee OA SF and its correlations with cartilage degradation and inflammation markers of OA support its participation in OA pathology.

SAMITAL® improves chemo/radiotherapy-induced oral mucositis in patients with head and neck cancer: results of a randomized, placebo-controlled, single-blind Phase II study.

PURPOSE: This randomised, placebo-controlled single-blind trial investigated the safety and efficacy of SAMITAL®, a formulation of highly standardised botanical extracts, in the treatment of chemo/radiotherapy-induced oral mucositis (OM) in patients with head and neck cancer. METHODS: Patients received SAMITAL® or placebo four times daily for up to 50 days during scheduled chemo/radiotherapy. Severity of OM was monitored according to a modified WHO severity scale, and pain and quality-of-life assessments were based on the effect of symptoms of OM on relevant daily activities, according to a visual analogue scale. RESULTS: Mean scores for the severity of OM were significantly (p < 0.05 versus baseline) reduced from day 31 until the end of treatment in patients treated with SAMITAL® (n = 20). No significant improvement was observed in the placebo group (n = 10). Pain reduction was significant from day 4 till end of treatment with SAMITAL® and from days 7 to 21 in placebo patients. SAMITAL® also significantly improved quality of life, as shown by improvements in scores for relevant daily activities including eating, drinking and sleeping. All SAMITAL® patients completed the treatment period, but no placebo recipients completed treatment. No severe adverse events were observed with SAMITAL®, and systemic absorption of relevant active ingredients was undetectable. CONCLUSIONS: SAMITAL® significantly decreased the severity of chemo/radiotherapy-induced OM in patients with head and neck cancer, with no treatment-related adverse events. Pain relief lasted through the treatment period, and improvements in quality of life were reflected by the significant benefits of SAMITAL® on activities like drinking, eating and speaking.

Salivary secretion effects of the antipsychotic drug olanzapine in an animal model.

OBJECTIVE: Olanzapine, introduced as an alternative to clozapine in schizophrenia therapy, is thought to display a receptor affinity similar to that of clozapine. Antipsychotics are well-known xerogenic drugs. However, clozapine exerts both antagonistic and agonistic salivary effects ('clozapine-induced sialorrhea'), the latter probably via muscarinic M1 type of receptor. We hypothesise that olanzapine also has dual salivary effects. MATERIAL AND METHODS: Effects of intravenous olanzapine were examined in rats, including those subjected to chronic preganglionic parasympathetic denervation (submandibular glands) or combined postganglionic parasympathetic and sympathetic denervation (parotid glands). Secretion was evoked reflexly, and by intravenous methacholine and the tachykinin substance P. RESULTS: At 0.01-1 mg kg(-1), olanzapine dose dependently reduced secretion in response to methacholine or reflex stimulus but not that to substance P. At 10 mg kg(-1), olanzapine evoked a long-lasting secretion, independent of the autonomic innervation as well as of α- and ß-adrenergic receptors and muscarinic receptors. The secretion was reduced, but not abolished, by a substance P receptor antagonist. CONCLUSIONS: Like clozapine, olanzapine evoked secretion. The response to olanzapine was greater and, in contrast to clozapine, involved non-traditional gland receptors (such as substance P receptors). The findings imply that olanzapine plays an excitatory role via tachykinin receptors in humans.

Single-nucleotide polymorphism-defined class I and class III major histocompatibility complex genetic subregions contribute to natural long-term nonprogression in HIV infection.

We performed a genome-wide association study comparing a cohort of 144 human immunodeficiency virus (HIV type 1-infected, untreated white long-term nonprogressors (LTNPs) with a cohort of 605 HIV-1-infected white seroconverters. Forty-seven single-nucleotide polymorphisms (SNPs), located from class I to class III major histocompatibility complex (MHC) subregions, show statistical association (false discovery rate, <0.05) with the LTNP condition, among which 5 reached genome-wide significance after Bonferonni correction. The MHC LTNP-associated SNPs are ordered in ≥4 linkage disequilibrium blocks; interestingly, an MHC class III linkage disequilibrium block (defined by the rs9368699 SNP) seems specific to the LTNP phenotype.

Neuroinflammation and status epilepticus: a narrative review unraveling a complex interplay.

Status epilepticus (SE) is a medical emergency resulting from the failure of the mechanisms involved in seizure termination or from the initiation of pathways involved in abnormally prolonged seizures, potentially leading to long-term consequences, including neuronal death and impaired neuronal networks. It can eventually evolve to refractory status epilepticus (RSE), in which the administration of a benzodiazepine and another anti-seizure medications (ASMs) had been ineffective, and super-refractory status epilepticus (SRSE), which persists for more than 24 h after the administration of general anesthesia. Objective of the present review is to highlight the link between inflammation and SE. Several preclinical and clinical studies have shown that neuroinflammation can contribute to seizure onset and recurrence by increasing neuronal excitability. Notably, microglia and astrocytes can promote neuroinflammation and seizure susceptibility. In fact, inflammatory mediators released by glial cells might enhance neuronal excitation and cause drug resistance and seizure recurrence. Understanding the molecular mechanisms of neuroinflammation could be crucial for improving SE treatment, wich is currently mainly addressed with benzodiazepines and eventually phenytoin, valproic acid, or levetiracetam. IL-1ß signal blockade with Anakinra has shown promising results in avoiding seizure recurrence and generalization in inflammatory refractory epilepsy. Inhibiting the IL-1ß converting enzyme (ICE)/caspase-1 is also being investigated as a possible target for managing drug-resistant epilepsies. Targeting the ATP-P2X7R signal, which activates the NLRP3 inflammasome and triggers inflammatory molecule release, is another avenue of research. Interestingly, astaxanthin has shown promise in attenuating neuroinflammation in SE by inhibiting the ATP-P2X7R signal. Furthermore, IL-6 blockade using tocilizumab has been effective in RSE and in reducing seizures in patients with febrile infection-related epilepsy syndrome (FIRES). Other potential approaches include the ketogenic diet, which may modulate pro-inflammatory cytokine production, and the use of cannabidiol (CBD), which has demonstrated antiepileptic, neuroprotective, and anti-inflammatory properties, and targeting HMGB1-TLR4 axis. Clinical experience with anti-cytokine agents such as Anakinra and Tocilizumab in SE is currently limited, although promising. Nonetheless, Etanercept and Rituximab have shown efficacy only in specific etiologies of SE, such as autoimmune encephalitis. Overall, targeting inflammatory pathways and cytokines shows potential as an innovative therapeutic option for drug-resistant epilepsies and SE, providing the chance of directly addressing its underlying mechanisms, rather than solely focusing on symptom control.

Berberine phospholipid exerts a positive effect on the glycemic profile of overweight subjects with impaired fasting blood glucose (IFG): a randomized double-blind placebo-controlled clinical trial.

OBJECTIVE: Berberine is a plant alkaloid known to exert positive metabolic effects. Human studies have confirmed its ability to improve the lipid and glycemic profile. This study aimed to evaluate the potential benefit of oral supplementation of Berberine PhytosomeTM (2 tablets/day, 550 mg/tablet) on the metabolic profile of subjects with impaired fasting blood glucose (IFG). PATIENTS AND METHODS: A total of 49 overweight subjects, 28 females and 21 males, were randomly assigned to either the supplemented group (n=24) or placebo (n=25). We considered glycemia as the primary endpoint and total cholesterol, high-density lipoprotein (HDL), total cholesterol/HLD, low-density lipoprotein (LDL), LDL/HDL, triglycerides, insulin, glycated hemoglobin, Homeostasis Model Assessment (HOMA), ApoA, ApoB, ApoB/ApoA, androgen suppression treatment (AST), alternative lengthening of telomeres (ALT), gamma-glutamyl transferase (GGT), creatinine, and body composition by dual-energy X-ray absorptiometry (DXA) as secondary endpoints. These parameters have been assessed at baseline, after 30 days, and after 60 days. RESULTS: After two months of treatment, through the use of linear mixed effect models, a statistically significant difference between supplemented and placebo groups was observed for glycemia [ß=-0.2495% C.I. (-0.47; -0.06), p=0.004], total cholesterol [ß=-0.25, 95% C.I. (-0.45; -0.04), p=0.05], total cholesterol/HDL [ß=-0.25, 95% C.I. (-0.43; -0.06), p=0.04], triglycerides [ß=-0.14, 95% C.I. (-0.25; -0.02), p=0.05], insulin [ß=-1.78, 95% C.I. (-2.87; -0.66), p=0.009], ApoB/ApoA [ß=-0.08, 95% C.I. (-0.13; -03), p=0.004], Visceral adipose tissue (VAT) [ß=-91.50, 95% C.I. (-132.60; -48.19), p<0.0001] and fat mass [ß=-945.56, 95% C.I. (-1,424.42; -441.57), p=0.004]. CONCLUSIONS: The use of berberine had no adverse events, supporting its use as a natural alternative to pharmacological therapies in the case of IFG.