Dinesenpaul4371

Endothelial cells and astrocytes preferentially express metabotropic P2Y nucleotide receptors, which are involved in the maintenance of vascular and neural function. Among these, P2Y1 and P2Y2 receptors appear as main actors, since their stimulation induces intracellular calcium mobilization and activates signaling cascades linked to cytoskeletal reorganization. In the present work, we have analyzed, by means of atomic force microscopy (AFM) in force spectroscopy mode, the mechanical response of human umbilical vein endothelial cells (HUVEC) and astrocytes upon 2MeSADP and UTP stimulation. This approach allows for simultaneous measurement of variations in factors such as Young's modulus, maximum adhesion force and rupture event formation, which reflect the potential changes in both the stiffness and adhesiveness of the plasma membrane. The largest effect was observed in both endothelial cells and astrocytes after P2Y2 receptor stimulation with UTP. Such exposure to UTP doubled the Young's modulus and reduced both the adhesion force and the number of rupture events. In astrocytes, 2MeSADP stimulation also had a remarkable effect on AFM parameters. Additional studies performed with the selective P2Y1 and P2Y13 receptor antagonists revealed that the 2MeSADP-induced mechanical changes were mediated by the P2Y13 receptor, although they were negatively modulated by P2Y1 receptor stimulation. Hence, our results demonstrate that AFM can be a very useful tool to evaluate functional native nucleotide receptors in living cells.

To investigate candidate genes associated with familial strabismus and propose a theory of their interaction in familial strabismus associated with early neurodevelopment.

Eighteen families, including 53 patients diagnosed with strabismus and 34 unaffected family members, were analyzed. All patients with strabismus and available unaffected family members were evaluated using whole exome sequencing. The primary outcome was to identify rare occurring variants among affected individuals and investigate the evidence of their genetic heterogeneity. These results were compared with exome sequencing analysis to build a comprehensive genetic profile of the study families.

We observed 60 variants from 58 genes in 53 patients diagnosed with strabismus. We prioritized the most credible risk variants, which showed clear segregation in family members affected by strabismus. As a result, we found risk variants in four genes (

,

, and

) in five families, suggesting their role in development of familial strabismus. In other families, there were several rare genetic variants in affected cases, but we did not find clear segregation pattern across family members.

Genomic sequencing holds great promise in elucidating the genetic causes of strabismus; further research with larger cohorts or other related approaches are warranted.

Genomic sequencing holds great promise in elucidating the genetic causes of strabismus; further research with larger cohorts or other related approaches are warranted.CXC-chemokine receptor type 4 (CXCR4), a 7-transmembrane receptor family member, displays multifaceted roles, participating in immune cell migration, angiogenesis, and even adipocyte metabolism. However, the activity of such a ubiquitously expressed receptor in epithelial gland organogenesis has not yet been fully explored. To investigate the relationship between CXCL12/CXCR4 signaling and embryonic glandular organogenesis, we used an ex vivo culture system with live imaging and RNA sequencing to elucidate the transcriptome and protein-level signatures of AMD3100, a potent abrogating reagent of the CXCR4-CXCL12 axis, imprinted on the developing organs. Immunostaining results showed that CXCR4 was highly expressed in embryonic submandibular gland, lung, and pancreas, especially at the periphery of end buds containing numerous embryonic stem/progenitor cells. Despite no significant increase in apoptosis, AMD3100-treated epithelial organs showed a retarded growth with significantly slower branching and expansion. Further analyses with submandibular glands revealed that such responses resulted from the AMD3100-induced precocious differentiation of embryonic epithelial cells, losing mitotic activity. RNA sequencing analysis revealed that inhibition of CXCR4 significantly down-regulated polycomb repressive complex (PRC) components, known as regulators of DNA methylation. Treatment with PRC inhibitor recapitulated the AMD3100-induced precocious differentiation. Our results indicate that the epigenetic modulation by the PRC-CXCR12/CXCR4 signaling axis is crucial for the spatiotemporal regulation of proliferation and differentiation of embryonic epithelial cells during embryonic glandular organogenesis.Endoscopic ultrasonography-guided gastroenterostomy using a lumen-apposing metal stent has emerged as a novel technique in the palliative treatment of malignant gastric outlet obstruction. Endoscopic ultrasonography-guided gastroenterostomy seems to have the potential to provide long-lasting patency in a minimally invasive manner. Low reintervention rates have been described. We report two cases with early lumen-apposing metal stent dysfunction, compromising patency. One case showed food impaction after three weeks, and hyperplastic tissue overgrowth with a buried distal flange six weeks after stent placement. The latter was successfully treated by argon plasma coagulation, stent removal, and deployment of a larger-diameter lumen-apposing metal stent. The second case showed a narrowed luminal diameter of the stent and jejunal pressure ulcerations after three weeks. The narrowing was successfully treated by balloon dilation. Eight weeks later, hyperplastic tissue overgrowth at the distal flange of the stent and a gastro-colonic fistula were diagnosed, followed by extensive reconstructive surgery.

A white substance that is opaque to endoscopic light is sometimes observed in the epithelium during narrowband imaging with magnifying endoscopy of gastric or colorectal epithelial neoplasms. This prospective observational study aimed to determine whether the morphology of the white opaque substance (WOS) allows differential diagnosis between colorectal adenoma and carcinoma.

A consecutive series of patients with colorectal adenomas or early carcinomas who underwent endoscopic resection or surgical excision were studied. The morphology of the WOS was determined based on endoscopic images before the histopathological diagnosis was performed. The primary outcome was the diagnostic performance of an irregular WOS as a marker of colorectal carcinoma.

The study analyzed 125 lesions. A total of 33 lesions showed an irregular WOS, and 92 lesions showed a regular WOS. Among the 33 lesions found to show an irregular WOS, 30 were carcinomas. Among the 92 lesions showing a regular WOS, 79 were adenomas. With irregular WOS as a marker of carcinoma, the diagnostic accuracy was 87%, sensitivity was 91%, and specificity was 86%.

This study demonstrated the potential usefulness of the morphology of the WOS as a marker for the differential diagnosis between adenoma and carcinoma in cases of colorectal epithelial neoplasms.

This study demonstrated the potential usefulness of the morphology of the WOS as a marker for the differential diagnosis between adenoma and carcinoma in cases of colorectal epithelial neoplasms.The present manuscript aims to review the history, recent advances, evidence, and challenges of artificial intelligence (AI) in colonoscopy. Although it is mainly focused on polyp detection and characterization, it also considers other potential applications (i.e., inflammatory bowel disease) and future perspectives. Some of the most recent algorithms show promising results that are similar to human expert performance. The integration of AI in routine clinical practice will be challenging, with significant issues to overcome (i.e., regulatory, reimbursement). Medico-legal issues will also need to be addressed. With the exception of an AI system that is already available in selected countries (GI Genius; Medtronic, Minneapolis, MN, USA), the majority of the technology is still in its infancy and has not yet been proven to reach a sufficient diagnostic performance to be adopted in the clinical practice. However, larger players will enter the arena of AI in the next few months.

This study aimed to examine the degree of clinical and functional improvement after paliperidone long-acting injectable (LAI) administration according to the duration of illness.

Patients with schizophrenia diagnosed by ICD-10 criteria who were planned to start once-monthly paliperidone LAI were recruited from 2010 to 2017. Clinical and functional changes were measured every 4 weeks using the Clinical Global Impressions-Severity of Illness scale (CGI-S) and Personal and Social Performance scale (PSP), respectively, for 6 months after paliperidone LAI initiation. Improvements after starting paliperidone LAI were compared among patients with duration of illness < 3 years, ≥ 3 and < 10 years, and ≥ 10 years.

A total of 1,166 participants (duration of illness < 3 years, n = 240; 3 ≤ duration of illness < 10 years, n = 442; duration of illness ≥ 10 years, n = 484) were enrolled. The total olanzapine-equivalent doses of antipsychotics and the LAI monotherapy proportion at the final visit were significantly different among the 3 duration of illness groups (dose F₂,₁₁₆₃ = 18.41, P < .001; monotherapy χ²₂ = 11.73, P = .003). The changes in CGI-S score were significantly different according to the duration of illness, and those with duration of illness < 3 years showed the best improvement (group × week χ²₁₂ = 25.33, P = .013). All 3 groups showed significantly improved PSP scores (week χ²₆ = 294.2, P < .001).

Starting paliperidone LAI significantly improved clinical and functional outcomes in patients with schizophrenia, especially those with shorter duration of illness. These findings suggest that LAI antipsychotic administration may be considered in early-stage schizophrenia for improved outcomes.

Starting paliperidone LAI significantly improved clinical and functional outcomes in patients with schizophrenia, especially those with shorter duration of illness. These findings suggest that LAI antipsychotic administration may be considered in early-stage schizophrenia for improved outcomes.

To assess the efficacy and safety of citalopram in the acute and maintenance phases of bipolar depression in a randomized, double-blind, placebo-controlled trial.

Between 2007 and 2014, 119 subjects with acute major depressive episodes diagnosed with DSM-IV bipolar disorder, type I or type II, were randomized blindly to citalopram or placebo, added to standard mood stabilizers. They were followed for 6 weeks for acute efficacy (primary outcome) and up to 1 year for maintenance efficacy (secondary outcome) using scores on the Montgomery-Asberg Depression Rating Scale (MADRS) and the Mania Rating Scale of the Schedule for Affective Disorders and Schizophrenia (MRS-SADS). The study was powered for a clinically meaningful effect size.

Mean ± SD MADRS scores changed from a baseline value of 27.4 ± 9.1 to 13.1 ± 8.4 at the end of the acute phase for citalopram versus a change from 27.4 ± 7.3 to 15.2 ± 9.9 for placebo, a clinically and statistically nonsignificant difference. Maintenance efficacy also was not better with citalopram than with placebo. Acute manic/hypomanic episodes were similar in both groups, and subjects with type II illness did not have better outcomes than subjects with type I illness. In maintenance treatment, MRS-SADS scores were greater overall, especially in subjects with a rapid-cycling illness course, with citalopram versus placebo.

Citalopram, added to standard mood stabilizers, did not have clinically meaningful benefit versus placebo for either acute or maintenance treatment of bipolar depression. Acute mania did not worsen with citalopram, but maintenance treatment led to worsened manic symptoms, especially in subjects with a rapid-cycling course.

ClinicalTrials.gov identifier NCT00562861.

ClinicalTrials.gov identifier NCT00562861.We report the interesting experience of the African Village of Hope (Dodoma, Tanzania) where HIV-positive orphan children have been hosted, cured, and educated in the last 15 years. The particular attention to beauty in the education of the children amazed us when we were in the village working as doctors. The project and the effort to create such a model of social and medical assistance were born from the idea of the founders, Sister Maria Rosaria Gargiulo and Don Vincenzo Boselli. In light of this experience and of the healthy result obtained in the village, we believe that education in the perception of beauty is a formative aspect for all children, but may also be a powerful adjuvant therapy in severely immunocompromised young patients.Eating quickly is associated with eating larger amounts at mealtimes and faster eaters tend to have a higher BMI. Evidence suggests that sibling structure influences the development of childhood eating behaviours. We hypothesized that number of siblings and birth order might play a role in the development of eating rate. In two UK studies, children in Bristol (n = 132; Study 1) and adults and children in London (adults n = 552, children n = 256; Study 2) reported their eating rate, number of siblings, and birth order. A BMI measurement was obtained and in Study 2 waist circumference was recorded. Ordered logistic regression was used to examine effects of sibling structure on eating rate and linear regression assessed effects of eating rate on BMI. Faster eating was associated with higher BMI and a larger waist, in children and adults (ps  less then  .01). In Study 1, first-born children were twice as likely to eat faster compared to children who were not first-born (P  less then  .04). In Study 2, only-child adults reported eating slower than adults who were not first-born (P  less then  .003). Additionally, higher number of siblings was associated with faster eating rate in children from Bristol (P  less then  .05), but not in children from London. London adults without siblings ate slower than those with two or more (P = .01), but having one sibling was associated with eating faster than having two or more (P = .01). These findings reveal how birth order and number of siblings might influence eating rate. Exploring these relationships through direct observation would be beneficial in future studies.

Secondary electrospray ionization (SESI) in a water spray environment at atmospheric pressure involves the reactions of hydrated hydronium reagent ions, H

O

(H

O)

, with trace analyte compounds in air samples. Understanding the formation and dehydration of reagent and analyte ions is the foundation for meaningful quantification of trace compounds by SESI-mass spectrometry (MS).

A numerical model based on gas-phase ion thermochemistry is developed that describes equilibria in H

O

(H

O)

reagent cluster ion distributions and ligand switching reactions with polar NH

molecules leading to equilibrated hydrated ammonium ions NH



(H

O)

. The model predictions are compared with experimental results obtained using a cylindrical SESI source coupled to an ion-trap mass spectrometer via a heated ion transfer capillary. Non-polar isoprene, C

H

, was used to further probe the nature of the reagent ions.

Equilibrium distributions of H

O

(H

O)

ions and their reactions with NH

moleenon is also predicted for other polar analyte molecules, A, that can undergo similar switching reactions, thus forming AH+ and AH+ (H2 O)m analyte ions.

The effort to make fake documents look real leads to the use of crickets and beverages to produce artificially aged papers, as land titles, based on yellowing caused by the use of these methods. An old practice in Brazil, called "cricketing", has led to the misappropriation of Brazilian land using these documents. We propose a rapid, simple, instantaneous and non-destructive method to identify artificially aged papers by easy ambient sonic-spray ionization mass spectrometry (EASI-MS) analysis.

Three typical aging procedures were used to obtain artificially aged papers using coffee, cola drink, and crickets, with the papers being analyzed by EASI-MS. Multivariate statistical analyses were performed on the data to find the sample groups and to study the most relevant ions of each ageing procedure. High-resolution MS (HRMS) was used to obtain the exact masses and attribute formulae to relevant ions present in the samples.

The combination of EASI-MS and multivariate statistical analyses allowed us to identify the most relevant ions to classify the adulteration of documents and HRMS identified most of these relevant ions. TMS fingerprinting in combination with multivariate analysis also demonstrated that this approach can qualitatively differentiate all the examined paper samples.

We developed a cheap, fast and easy method that can help to elucidate counterfeit documents that have been artificially aged, helping to identify chemical additives and one that can be used in forensic laboratories.

We developed a cheap, fast and easy method that can help to elucidate counterfeit documents that have been artificially aged, helping to identify chemical additives and one that can be used in forensic laboratories.

Inflammation associated with the tumour microenvironment (TME) is critical for cancer development, and immunotherapeutic strategies modulating the immune response in cancer have been crucial. In this study, a methotrexate-loaded (MTX) poly(lactic-co-glycolic acid)-based (PLGA) drug nanocarrier covered with polyethyleneimine (Pei) and hyaluronic acid (HA) was developed and combined with an PD-L1 antibody to investigate anti-cancer and immunomodulatory effects in breast cancer TME.

Naked or HA-coated PeiPLGA-MTX nanoparticles (NPs) were assessed on 4T1 breast cancer cells grown in culture and in a mouse model of orthotopic tumour growth. Tumours were evaluated by qRT-PCR and immunohistochemistry. The cell death profile and cell migration were analysed in vitro in 4T1 cells. Polarization of murine macrophages (RAW cells) was also carried out.

Naked or HA-coated PeiPLGA-MTX NPs used alone or combined with PD-L1 antibody modified the tumourigenic course by TME immunomodulation, leading to reduction of primarof breast cancer.

Various rehabilitation treatments may be offered following surgery for flexor tendon injuries of the hand. Rehabilitation often includes a combination of an exercise regimen and an orthosis, plus other rehabilitation treatments, usually delivered together. The effectiveness of these interventions remains unclear.

To assess the effects (benefits and harms) of different rehabilitation interventions after surgery for flexor tendon injuries of the hand.

We searched the Cochrane Central Register of Controlled Trials, the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, MEDLINE, Embase, two additional databases and two international trials registries, unrestricted by language. The last date of searches was 11 August 2020. We checked the reference lists of included studies and relevant systematic reviews.

We included randomised controlled trials (RCTs) and quasi-RCTs that compared any postoperative rehabilitation intervention with no intervention, control, placebo, or another postoperative blishing minimum study conduct and reporting criteria will be valuable. Our suggestions for future research are detailed in the review.

Ilexgenin A is a triterpenoid from ShanLv Cha with beneficial effects on metabolic homeostasis. We investigated whether ilexgenin A could inhibit hepatic de novo fatty acid synthesis via the interfering with SREBP1 maturation.

The effects of Ilexgenin A on CRTC2 translocation and SREBP1 maturation were investigated in the liver of fasted mice and hepatocytes exposed to saturated fatty acids. The effect of Iilexgenin A on hepatic lipid accumulation was also observed in high-fat diet fed mice.

Sec23A and Sec31A are two subunits of COPII complex and their interaction is essential for the processing of SREBP1 maturation. Ilexgenin A activates AMPK by reducing cellular energy and preventing cytoplasmic CRTC2 to compete with Sec23A for binding to Sec31A under nutrient-rich conditions. Consequently, ilexgenin A impaired COPII-dependent SREBP1 maturation via disrupting Sec31A-Sec23A interaction, leading to the inhibition of de novo fatty acid synthesis in the liver. In contrast, mTORC1 phosphorylated Ser136 of s section visit http//onlinelibrary.wiley.com/doi/10.1111/bph.v179.5/issuetoc.

The metabolic activity of cytochrome P450 (CYP) 2D6 is highly variable and CYP2D6 genotypes insufficiently explain the extensive and intermediate metabolic phenotypes, limiting the prediction of drug response plus adverse drug reactions. Since CYP2D6 prototypic substrates are positively charged, the aim of this study was to evaluate the organic cation transporters (OCTs) and multidrug and toxin extrusion proteins (MATEs) as potential contributors to the variability of CYP2D6 hydroxylation of debrisoquine, dextromethorphan, diphenhydramine, perhexiline and sparteine.

OCT1/SLC22A1-, OCT2/SLC22A2-, OCT3/SLC22A3-, MATE1/SLC47A1-, and MATE2K/SLC47A2-overexpressing cell lines were used to investigate the transport of the selected drugs. Individuals from a study cohort, well defined with respect to CYP2D6 genotype and sparteine pharmacokinetics, were genotyped for the common OCT1 variants rs12208357 (OCT1-R61C), rs34130495 (OCT1-G401S), rs202220802 (OCT1-Met420del), rs34059508 (OCT1-G465R), OCT2 variant rs316019xylation in extensive and intermediate metabolizers cannot be explained by OCT1 genetic variants indicating presence of other factors. Dose-dependent toxicities of dextromethorphan, diphenhydramine and perhexiline appear to be independent from OCTs and MATEs.

Bronchopulmonary dysplasia (BPD) is the most prevalent chronic paediatric lung disease and is linked to the development of chronic obstructive pulmonary disease. MicroRNA-based regulation of type II alveolar epithelial cell (T2AEC) proliferation and apoptosis is an important factor in the pathogenesis of BPD and warrants further investigation.

Two murine models of hyperoxic lung injury (with or without miR-342-5p or Sprouty-related, EVH1 domain-containing protein 3 [Spred3] modulation) were employed a hyperoxia-induced acute lung injury model (100% O

on postnatal days 1-7) and the BPD model (100% O

on postnatal days 1-4, followed by room air for 10 days). Tracheal aspirate pellets from healthy control and moderate/severe BPD neonates were randomly selected for clinical miR-342-5p analysis.

Hyperoxia decreased miR-342-5p levels in primary T2AECs, MLE12 cells and neonatal mouse lungs. Transgenic miR-342 overexpression in neonatal mice ameliorated survival rates and improved the BPD phenotype and BPD-associated pulmonary arterial hypertension (PAH). T2AEC-specific miR-342 transgenic overexpression, as well as miR-342-5p mimic therapy, also ameliorated the BPD phenotype and associated PAH. miR-342-5p targets the 3'UTR of the Raf1 regulator Spred3, inhibiting Spred3 expression. Treatment with recombinant Spred3 exacerbated the BPD phenotype and associated PAH. Notably, miR-342-5p inhibition under room air conditions did not mimic the BPD phenotype. Moderate/severe BPD tracheal aspirate pellets exhibited decreased miR-342-5p levels relative to healthy control pellets.

These findings suggest that miR-342-5p mimic therapy may show promise in the treatment or prevention of BPD.

These findings suggest that miR-342-5p mimic therapy may show promise in the treatment or prevention of BPD.General anaesthesia for obstetric surgery has distinct characteristics that may contribute towards a higher risk of accidental awareness during general anaesthesia. The primary aim of this study was to investigate the incidence, experience and psychological implications of unintended conscious awareness during general anaesthesia in obstetric patients. From May 2017 to August 2018, 3115 consenting patients receiving general anaesthesia for obstetric surgery in 72 hospitals in England were recruited to the study. Patients received three repetitions of standardised questioning over 30 days, with responses indicating memories during general anaesthesia that were verified using interviews and record interrogation. A total of 12 patients had certain/probable or possible awareness, an incidence of 1 in 256 (95%CI 149-500) for all obstetric surgery. The incidence was 1 in 212 (95%CI 122-417) for caesarean section surgery. Distressing experiences were reported by seven (58.3%) patients, paralysis by five (41.7%) and paralysis with pain by two (16.7%). Accidental awareness occurred during induction and emergence in nine (75%) of the patients who reported awareness. Factors associated with accidental awareness during general anaesthesia were high BMI (25-30 kg.m-2 ); low BMI ( less then 18.5 kg.m-2 ); out-of-hours surgery; and use of ketamine or thiopental for induction. Standardised psychological impact scores at 30 days were significantly higher in awareness patients (median (IQR [range]) 15 (2.7-52.0 [2-56]) than in patients without awareness 3 (1-9 [0-64]), p = 0.010. Four patients had a provisional diagnosis of post-traumatic stress disorder. We conclude that direct postoperative questioning reveals high rates of accidental awareness during general anaesthesia for obstetric surgery, which has implications for anaesthetic practice, consent and follow-up.

 The aim of this study was to determine the prevalence of acute traumatic coagulopathy (ATC) and identify associated clinical and laboratory parameters including rotational thromboelastometry.

 Dogs presenting within 6 hours after trauma were allocated to the ATC or non-ATC group based on thromboelastometry analysis (ex-tem S, in-tem S, fib-tem S). ATC was defined as ≥2 hypocoagulable parameters in 1 profile and ≥ 1 hypocoagulable parameter in an additional profile. Parameters used were ex-tem and in-tem clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), maximum lysis and fib-tem MCF. Clinical and laboratory parameters at presentation, animal trauma triage (ATT) score, transfusion requirement and outcome were compared. Logistic regression was used to identify independent factors associated with ATC.

 Eleven of 33 dogs presented with ATC and showed ex-tem CT and CFT prolongation and reduced MCF amplitude in all profiles (all

 0.001). pH (

0.043) and potassium concentration (

 0.022) were significantly lower and bleeding (

0.027) and plasma transfusions

0.001

more common in dogs with ATC. Time after trauma (

0.040) and Animal Trauma Triage score (

0.038, including haematocrit as confounding factor) were associated with the presence of ATC.

 Acute traumatic coagulopathy is more common in traumatized dogs than previously reported. Acute traumatic coagulopathy was associated with acidosis, Animal trauma triage score, time after trauma and higher transfusion needs. Coagulation abnormalities include ex-tem CT and CFT prolongations and decreased clot strength.

 Acute traumatic coagulopathy is more common in traumatized dogs than previously reported. Acute traumatic coagulopathy was associated with acidosis, Animal trauma triage score, time after trauma and higher transfusion needs. Coagulation abnormalities include ex-tem CT and CFT prolongations and decreased clot strength.

Conventional treatment guidelines of schizophrenia do not necessarily provide solutions on clinically important issues.

A total of 141 certified psychiatrists of the Japanese Society of Clinical Neuropsychopharmacology evaluated treatment options regarding 19 clinically relevant situations in the treatment of schizophrenia with a 9-point scale (1="disagree" and 9="agree").

First-line antipsychotics varied depending on predominant symptoms risperidone (mean±standard deviation score, 7.9±1.4), olanzapine (7.5±1.6), and aripiprazole (6.9±1.9) were more likely selected for positive symptoms; aripiprazole (7.6±1.6) for negative symptoms; aripiprazole (7.3±1.9), olanzapine (7.2±1.9), and quetiapine (6.9±1.9) for depression and anxiety; and olanzapine (7.9±1.5) and risperidone (7.5±1.5) for excitement and aggression. While only aripiprazole was categorized as a first-line treatment for relapse prevention (7.6±1.0) in patients without noticeable symptoms, aripiprazole (8.0±1.6) and brexpiprazole (6.9±2.3) were categorized as such for social integration. First-line treatments in patients who are vulnerable to extrapyramidal symptoms include quetiapine (7.5±2.0) and aripiprazole (6.9±2.1).

These clinical recommendations represent the expert consensus on the use of a particular antipsychotic medication for a particular situation, filling a current gap in the literature.

These clinical recommendations represent the expert consensus on the use of a particular antipsychotic medication for a particular situation, filling a current gap in the literature.Vesicoureteral reflux (VUR) is a common urological complication in renal transplant patients.

of this study is to evaluate the performance of contrast-enhanced voiding urosonography (CEvUS) in the diagnosis and classification of reflux into the renal allograft, to evaluate and classify VUR into the allograft using voiding cystourethrography (VCUG) and CEvUS, to compare the two methods, and to propose a new classification of reflux into the allograft based on CEvUS and VCUG assessment, in line with the international reflux grading system.

 From January 2017 to July 2019, 84kidney transplant patients were enrolled. All patients underwent VCUG and CEvUS.

 In 76 cases there was agreement between VCUG and CEvUS (90 %) (Kappa = 0.7). The sensitivity of CEvUS using VCUG as the gold standard was 90 %, and the specificity was 92 %. Of the 7 cases diagnosed by VCUG and not by CEvUS, 6were grade 1 and 1 was grade 2.

 Transplant patients with reflux symptoms should undergo CEvUS. If the outcome is negative, VCUG should be performed. The classification that we propose is better suited to describe VUR in transplant patients, because it is simpler and takes into account whether reflux occurs not only during urination but also when the bladder is relaxed.

 Transplant patients with reflux symptoms should undergo CEvUS. If the outcome is negative, VCUG should be performed. The classification that we propose is better suited to describe VUR in transplant patients, because it is simpler and takes into account whether reflux occurs not only during urination but also when the bladder is relaxed.Medicinal plants and their extracts are natural remedies with enormous potential for treating various diseases, including depression and anxiety. In the case of depression, hundreds of plants have traditionally been used in folk medicine for generations. Different plant extracts and natural products have been analyzed as potential antidepressant agents with validated models to test for antidepressant-like effects in animals, although other complementary studies have also been employed. Most of these studies focus on the possible mediators implicated in these potential effects, with dopamine, serotonin, and noradrenaline being the principal neurotransmitters implicated, both through interference with receptors and with their metabolism by monoamino oxidases, as well as through neuro-endocrine and neuroprotective effects. There are approximately 650 reports of antidepressant-like medicinal plants in PubMed; 155 of them have been compiled in this review, with a relevant group yielding positive results. Saffron and turmeric are the most relevant species studied in both preclinical and clinical studies; St. John's wort or kava have also been tested extensively. To the best of our knowledge, no review to date has provided a comprehensive understanding of the biomolecular mechanisms of action of these herbs or of whether their potential effects could have real benefits. The purpose of this narrative review is to provide an update regarding medicinal plants from the year 2000 to the present to examine the therapeutic potential of these antidepressant-like plants in order to contribute to the development of new therapeutic methods to alleviate the tremendous burden that depression causes worldwide.Lime flowers, traditionally used for medical purposes for the treatment of symptoms of the common cold and mental stress, consist of the dried inflorescences including the floral bracts of Tilia cordata, Tilia platyphyllos, Tilia × vulgaris, or mixtures thereof. During phytochemical investigations, 6 different alkaloids - not described until now - were detected in T. cordata and T. platyphyllos flowers. They have been isolated and characterized as alkaloids with a dihydro-pyrrole and a piperidine substructure, respectively. Compounds 1A and 1B (tiliines A and B) are characterized as 2 diastereomers containing a 2-methyl-3,4-dihydro-2H-pyrrol-3-ol, connected via a C-10 alkyl chain to a O-glucosylated hydroquinone moiety. Compounds 2A and 2B (tiliamines A and B) are diastereomers of a 2-methyl-substituted piperidin-3-ol, coupled via a C-9 alkyl chain again to an O-glucosylated hydroquinone moiety. Compounds 3A and 3B (tilacetines A and B) are 3-O-acetylated derivatives of tiliamines. Quantification of the 6 alkaloids by HPLC-ESI-qTOF analysis indicated the presence of all alkaloids in T. cordata flowers and T. platyphyllos flowers, bracts, and leaves, with tiliines A and B and tilacetines A and B being the major compounds. Acetone/water turned out be the best extraction solvent for the alkaloids, but ethanol and ethanol/water mixtures also can be used for effective extraction. Furthermore, the alkaloids are found in hot water extracts, which are typically used in the traditional medicine.Manuka oil, an essential oil derived from the Leptospermum scoparium, has been traditionally used for wound care and as a topical antibacterial, antifungal, and anti-inflammatory. However, the essential oil is not well retained at mucosal sites, such as the oral cavity, where the benefits of the aforementioned properties could be utilized toward the treatment of persistent biofilms. Within this study, L. scoparium essential oil was incorporated into a semisolid emulsion for improved delivery. The safety profile of L. scoparium essential oil on human gingival fibroblasts was determined via cell viability, cytotoxicity, and caspase activation. The minimal bactericidal concentration of L. scoparium essential oil was determined, and the emulsion's antibiofilm effects visualized using confocal laser scanning microscopy. L. scoparium essential oil demonstrated a lower IC50 (0.02% at 48 h) when compared to the clinical control chlorhexidine (0.002% at 48 h) and displayed lower cumulative cytotoxicity. Higher concentrations of L. scoparium essential oil (≥ 0.1%) at 6 h resulted in higher caspase 3/7 activation, suggesting an apoptotic pathway of cell death. A minimal bactericidal concentration of 0.1% w/w was observed for 6 oral bacteria and 0.01% w/v for Porphyromonas gingivalis. Textural and rheometric analysis indicated increased stability of emulsion with a 1  3 ratio of L. scoparium essential oil Oryza sativa carrier oil. The optimized 5% w/w L. scoparium essential oil emulsion showed increased bactericidal penetrative effects on Streptococci gordonii biofilms compared to oil alone and to chlorhexidine controls. This study has demonstrated the safety, formulation, and antimicrobial activity of L. scoparium essential oil emulsion for potential antibacterial applications at mucosal sites.The content of the flavonolignan mixture silymarin and its individual components (silichristin, silidianin, silibinin A, silibinin B, isosilibinin A, and isosilibinin B) in whole and milled milk thistle seeds (Silybi mariani fructus) was analyzed with near-infrared spectroscopy. The analytical performance of one benchtop and two handheld near-infrared spectrometers was compared. Reference analysis was performed with HPLC following a Soxhlet extraction (European Pharmacopoeia) and a more resource-efficient ultrasonic extraction. The reliability of near-infrared spectral analysis determined through partial least squares regression models constructed independently for the spectral datasets obtained by the three spectrometers was as follows. The benchtop device NIRFlex N-500 performed the best both for milled and whole seeds with a root mean square error of CV between 0.01 and 0.17%. The handheld spectrometer MicroNIR 2200 as well as the microPHAZIR provided a similar performance (root mean square error of CV between 0.01 and 0.18% and between 0.01 and 0.23%, respectively). We carried out quantum chemical simulation of near-infrared spectra of silichristin, silidianin, silibinin, and isosilibinin for interpretation of the results of spectral analysis. This provided understanding of the absorption regions meaningful for the calibration. Further, it helped to better separate how the chemical and physical properties of the samples affect the analysis. While the study demonstrated that milling of samples slightly improves the performance, it was deemed to be critical only for the analysis carried out with the microPHAZIR. This study evidenced that rapid and nondestructive quantification of silymarin and individual flavonolignans is possible with miniaturized near-infrared spectroscopy in whole milk thistle seeds.

To determine the association between autoantibodies to G-protein-coupled receptors with effect on the cardiovascular system and the cardiac biomarker N-terminal pro-brain natriuretic peptide reflecting heart function in Graves' disease.

Sixty premenopausal women with Graves' disease were analyzed for IgG autoantibodies against β

-adrenergic, muscarinic acetylcholine type 2 and angiotensin II type 1 receptors using enzyme-linked immunosorbent assays based on cell membranes overexpressing receptors in their native conformations. N-terminal pro-brain natriuretic peptide and heart symptoms were analyzed in hyperthyroidism and after 7.5 months of antithyroid treatment. Matched thyroid healthy controls were also assessed.

Serum levels of antibodies against the β

-adrenergic and the muscarinic acetylcholine type 2 receptors were higher in hyperthyroid patients than in controls (median β

-adrenergic receptor antibodies 1.9 [IQR 1.3-2.7]

1.1 [0.8-1.7] μg/mL,

<0.0001; muscarinic acetylcholine type 2 rert cannot be excluded in subpopulations, as the functional properties of the analyzed antibodies remain to be determined.

Neonates are highly vulnerable to preventable medication errors due to their extensive exposure to medications in the neonatal intensive care units (NICUs). These errors, which can be made by medical, nursing, or pharmacy personnel, are costly and can be life-threatening. This study aimed to investigate the newly developed computerized neonatal pharmaceutical health care system (NPHCS) in terms of its ability to (1) minimize neonatal medication prescription errors (NMPEs) and (2) improve workflow efficiency compared with the traditional manual prescribing approach.

A computerized neonatal medication prescription system was designed, developed, and tested successfully through a pilot clinical trial for over 6 months in 100 neonates. A three phase quasi-experimental study was then conducted using standardized monitoring checklists for the assessment of NMPEs before and after utilization of the developed prescribing system.

The obtained result showed a high rate of NMPEs in both systems, especially for theion of medical records, compared with the traditional handwritten approach.Coronavirus disease (COVID-19) emerged from Wuhan, has now become pandemic and the mortality rate is growing exponentially. Clinical complication and fatality rate is much higher for patients having co-morbid issues. Compromised immune response and hyper inflammation is hall mark of pathogenesis and major cause of mortality. Cytokine release syndrome (CRS) or cytokine storm is a term used to affiliate the situation of hyper inflammation and therefore use of anti-cytokine and anti-inflammatory drugs is used to take care of this situation. Looking into the clinical benefit of these anti-inflammatory drugs, many of them enter into clinical trials. However, understanding the immunopathology of COVID-19 is important otherwise, indiscriminate use of these drugs could be fetal as there exists a very fine line of difference between viral clearing cytokines and inflammatory cytokines. If any drug suppresses the viral clearing cytokines, it will worsen the situation and hence, the use of these drugs must be based on the clinical condition, viral load, co-existing disease condition and severity of the infection.Reaction of piperazine with chloroacetylchloride in dry acetone yield compound 1 , which on reaction with hydrazine hydrate yielded compound 2 , which was further reacted with various substituted phenylisothiocyanates in absolute alcohol to afford compounds 3-8 i. e. 2-(carbazolylacetyl)-N-(substitutedphenyl)-hydrazinepiperazinothioamides. Compounds 3-8 on reaction with aqueous NaOH, ethanolic NaOH and conc. H2SO4 afford triazoles 9-14 , oxadiazoles 15-20 and thiadiazoles 21-26 respectively. Twenty four newly synthesized compounds were evaluated for their anticonvulsant activity and acute toxicity. The structures of these compounds were established on the basis of analytical and spectral data.Premature ovarian insufficiency (POI) and early menopause, defined as loss of ovarian activity prior to 40 years or menopause between the ages of 40 and 45 years, respectively, is associated with significant adverse health impacts. Recent data indicate that the prevalence of POI and early menopause is greater than was previously thought, affecting more than 10% of women. Biopsychosocial risk factors including genetic, autoimmune, reproductive, lifestyle, early-life, social/environmental, and iatrogenic have been associated with POI/early menopause or earlier age at menopause. However, establishing a causal role and the underlying mechanisms remains elusive. Understanding and clarification of these risk factors will facilitate prevention and risk minimization strategies to optimize women's health.CAMP (Cathelicidin antimicrobial peptide) is synthesized and secreted by adipocytes and involved in adipose tissue (AT) innate immune response and host defense of subcutaneous AT against Gram positive bacteria. Data on the regulation of CAMP in obesity and during weight loss are scarce and reference values do not exist. Serum CAMP levels (ELISA) and AT gene expression levels (quantitative real time PCR) were investigated in two large and longitudinal (12 months) cohorts of severely obese patients undergoing either a low calorie diet (LCD; n=79) or bariatric surgery (BS; n=156). The impact of metabolic factors on CAMP expression in vitro was investigated in differentiated 3T3-L1 adipocytes. CAMP serum levels significantly increased after BS but not during LCD. Females had lower CAMP serum levels and lower gene expression levels in subcutaneous AT. CAMP was positively correlated to unfavorable metabolic factors/adipokines and negatively to favorable factors/adipokines. CAMP gene expression was higher in subcutaneous than in visceral AT but serum CAMP levels were not correlated to levels of AT gene expression. While certain bile acids upregulated CAMP expression in vitro, high glucose/insulin as well as GLP-1 had an inhibitory effect. There exist gender-specific and AT compartment-specific effects on the regulation of CAMP gene expression. Weight loss induced by BS (but not by LCD) upregulated CAMP serum levels suggesting the involvement of weight loss-independent mechanisms in CAMP regulation such as bile acids, incretins and metabolic factors. CAMP might represent an adipokine at the interface between metabolism and innate immune response.The eye, like all organs, is exposed to the effects of the body's endocrine system. In addition, however, local branches of the endocrine system control important organ-specific functions, such as the production and drainage of aqueous humour. Similarly, the eye as a sensory organ acts back on endocrine controlled functions of the body, for example the day-night rhythm. This article aims to illustrate the physiological and pathological interactions of the eye and the endocrine functions of the body in the context of glaucoma. 1. The renin-angiotensin-aldosterone system, which as a local system is involved in the control of aqueous humour production and outflow. 2. The hormone endothelin, which as a strong vasoconstrictor plays a role in the dysregulated perfusion of the optic nerve and retina, and 3. the disruption of the day-night rhythm in advanced glaucoma, which is thought to be caused by damage to light-sensitive ganglion cells.

Until now, venous pressure within the eye has widely been equated with intraocular pressure (IOP). Measurements with dynamometers calibrated in instrument units or in force showed that the retinal venous pressure (RVP) may be higher than the IOP in glaucoma patients. In this study, the RVP was measured with a contact lens dynamometer calibrated in mmHg.

Study type cross-sectional.

Fifty consecutive patients with primary open-angle glaucoma (POAG) who underwent diurnal curve measurement under medication. Age 69 ± 8 years. Measurement of RVP contact lens dynamometry. IOP measurement dynamic contour tonometry.

Pressures are given in mmHg. In all 50 patients, the IOP was 15.9 (13.6; 17.1) [median (Q1; Q3)], and the RVP was 17.4 (14.8; 27.2). The distribution of the IOP was normal and that of the RVP was right skewed. In the subgroup of 34patients with spontaneous pulsation of the central retinal vein (SVP), the IOP and therefore, by definition, the RVP was 16.5 (13.7; 17.4). In the subgroup of 16 patientses may be much more compromised in this group of patients than has been assumed. They may be identified by a missing SVP. Topical and systemic medications showed no statistically significant influence on the RVP, except for the systemic

-blockers, in which the RVP was lower by 4.6 mmHg than for the patients who did not receive these drugs (p = 0.003).

In a subgroup of 16 of the 50 patients studied, the RVP was greater than the IOP by a highly statistically and clinically significant degree. According to the widely accepted thinking on the pathophysiology of retinal and optic nerve head circulation, the blood flow in these tissues may be much more compromised in this group of patients than has been assumed. They may be identified by a missing SVP. Topical and systemic medications showed no statistically significant influence on the RVP, except for the systemic β-blockers, in which the RVP was lower by 4.6 mmHg than for the patients who did not receive these drugs (p = 0.003).

Regional lymphadenectomy for urothelial carcinoma of the upper urinary tract is sometimes avoided in older patients to reduce surgical burden. We aimed to evaluate the therapeutic impact of lymphadenectomy in older patients undergoing curative therapy for upper urinary tract urothelial carcinoma.

The patients with urothelial carcinoma of the upper urinary tract older than 75years at the time of surgery and without lymph node or distant metastasis who underwent curative therapy at two tertiary hospitals between 1994 and 2019 were retrospectively analyzed. Complete-lymphadenectomy was performed as per our protocol. Cancer-specific survival, overall survival and metastasis-free survival after surgery were evaluated between complete-lymphadenectomy and no/incomplete-lymphadenectomy groups before and after 11 propensity score matching.

The original cohort included 150 patients (median age, 80.71years), and complete-lymphadenectomy was performed in 42 (28.00%) patients. Patients in complete-lymphadenectomy group were younger and less likely to be aged >80years (both, P<0.0001). After matching, 30 patients were allocated to each group and the ages were comparable (78.58 vs. 77.48years, P=0.1738). High-grade perioperative complication rates did not differ between groups both before and after matching. Cancer-specific survival, overall survival and metastasis-free survival were significantly longer in the complete-lymphadenectomy group both before and after matching (all, P<0.05).

This study suggests that complete-lymphadenectomy may provide therapeutic benefits for older patients. The decision to perform complete-lymphadenectomy must be based on the patient's physical condition, rather than his/her chronological age.

This study suggests that complete-lymphadenectomy may provide therapeutic benefits for older patients. The decision to perform complete-lymphadenectomy must be based on the patient's physical condition, rather than his/her chronological age.

Worldwide, high systolic blood pressure is the leading risk factor for deaths and disability-adjusted life-years but has been historically under-detected. This study aimed to quantify differences between estimated and practice-detected prevalences of hypertension across English general practices, and to determine how variations in detected prevalence could be explained by population-level and service-level factors.

Descriptive statistics, pair wise correlations between the independent variables and a multivariable regression analysis were undertaken. In the regression model, the outcome was detected hypertension prevalence, adjusted for estimated prevalence, person-related and disease-related determinants of illness and characteristics of general practices.

Detected prevalence was substantially lower than estimated prevalence (mean difference 16.23%; standard deviation 2.88%). Higher detected prevalence was associated with increased deprivation, increased non-white ethnicity and urban location. Lower detected prevalence was associated with larger list sizes, more general practitioners and being located in the South outside London. The final multivariable model's adjusted R2 value was 0.75.

Substantial under-detection of hypertension is widespread across England. Independent of estimated prevalence, factors associated with greater morbidity and population density predicted higher detected prevalence. Identifying patients with undetected hypertension and coordinating care for these patients will require further resources and logistical support in community settings.

Substantial under-detection of hypertension is widespread across England. Independent of estimated prevalence, factors associated with greater morbidity and population density predicted higher detected prevalence. Identifying patients with undetected hypertension and coordinating care for these patients will require further resources and logistical support in community settings.