Synthesis, Characterization and Antimicrobial Studies of Some Novel 1,3,4-Thiadiazolium-2-thiolate Derivatives

In this study, ten new 5-substituted-3-[4,6-di(morpholine-4-yl)-1,3,5-triazine 2-yl]-1,3,5-thiadiazolium-2-thiolate 6(a–j) were prepared via a five step procedure from the starting material 1,3,5-triazine (1). Structures of all synthesized compounds were confirmed by spectral data and elemental analyses. Newly synthesized compounds were tested for their antibacterial and antifungal activities against some important bacterial and fungal species. Some of the compounds were found to be moderately active against the tested organisms.Keywords: Thiadiazol, s-triazine, Mesoionic, NMR spectroscopy, IR spectroscop

In vivo compartmental analysis of leukocytes in mouse lungs

The lung has a unique structure consisting of three functionally different compartments (alveolar, interstitial, and vascular) situated in an extreme proximity. Current methods to localize lung leukocytes using bronchoalveolar lavage and/or lung perfusion have significant limitations for determination of location and phenotype of leukocytes. Here we present a novel method using in vivo antibody labeling to enable accurate compartmental localization/quantification and phenotyping of mouse lung leukocytes. Anesthetized C57BL/6 mice received combined in vivo intravenous and intratracheal labeling with fluorophore-conjugated anti-CD45 antibodies, and lung single-cell suspensions were analyzed by flow cytometry. The combined in vivo intravenous and intratracheal CD45 labeling enabled robust separation of the alveolar, interstitial, and vascular compartments of the lung. In naive mice, the alveolar compartment consisted predominantly of resident alveolar macrophages. The interstitial compartment, gated by events negative for both intratracheal and intravenous CD45 staining, showed two conventional dendritic cell populations, as well as a Ly6C(lo) monocyte population. Expression levels of MHCII on these interstitial monocytes were much higher than on the vascular Ly6C(lo) monocyte populations. In mice exposed to acid aspiration-induced lung injury, this protocol also clearly distinguished the three lung compartments showing the dynamic trafficking of neutrophils and exudative monocytes across the lung compartments during inflammation and resolution. This simple in vivo dual-labeling technique substantially increases the accuracy and depth of lung flow cytometric analysis, facilitates a more comprehensive examination of lung leukocyte pools, and enables the investigation of previously poorly defined “interstitial” leukocyte populations during models of inflammatory lung diseases

Home Parenteral Nutrition in Patients with Advanced Cancer: A Systematic Review and Meta-Analysis

The use of home parenteral nutrition (HPN) in patients with incurable cancer remains controversial with significant variation worldwide. We aimed to systematically evaluate the literature from 1960 to 2018 examining the use of HPN in advanced cancer patients for all intestinal failure indications and assess the potential benefits/burdens of HPN in this cohort of patients. The primary end point was survival and secondary end points were quality of life and nutritional/performance status. Meta-analysis was performed with a random effects model, where suitable. Of 493 studies retrieved, 22 met the quality inclusion criteria. Studies were mainly conducted in Western countries (Italy, USA, Canada, Germany), including a total of 3564 patients (mean age 57.8 years). Mean duration for HPN was 5.0 mo. Mean overall survival was 7.3 mo. Patients with improved performance status survived for longer on HPN. Quality of life was sparsely reported though there was no observed negative impact of PN. HPN-related complications were reported in eight studies only and were mainly catheter-related blood stream infections. In conclusion, HPN is used for several indications in advanced cancer, though there is significant heterogeneity of results. Disparities in geographical distribution of the studies may reflect variation in accessing HPN

Biology of advanced uveal melanoma and next steps for clinical therapeutics

Uveal melanoma is the most common intraocular malignancy although it is a rare subset of all melanomas. Uveal melanoma has distinct biology relative to cutaneous melanoma, with widely divergent patient outcomes. Patients diagnosed with a primary uveal melanoma can be stratified for risk of metastasis by cytogenetics or gene expression profiling, with approximately half of patients developing metastatic disease, predominately hepatic in location, over a 15-yr period. Historically, no systemic therapy has been associated with a clear clinical benefit for patients with advanced disease, and median survival remains poor. Here, as a joint effort between the Melanoma Research Foundation's ocular melanoma initiative, CURE OM and the National Cancer Institute, the current understanding of the molecular and immunobiology of uveal melanoma is reviewed, and on-going laboratory research into the disease is highlighted. Finally, recent investigations relevant to clinical management via targeted and immunotherpies are reviewed, and next steps in the development of clinical therapeutics are discussed

Independent Commission on UK Public Health Emergency Powers:Final Report

The Independent Commission on UK Public Health Emergency Powers reviewed emergency public health laws and parliamentary procedures in the four UK nations. We considered how far these laws and procedures could be enhanced so as to better protect the rule of law and promote accountability, transparency and parliamentary control of executive action. We also undertook comparative research; reviewing public health emergency powers in ten foreign jurisdictions chosen because of their similarities to the UK’s parliamentary system and the efficacy of their legal responses to Covid-19. Throughout our inquiry we kept foremost in our minds the need for governments to act quickly in an emergency to secure timely and effective public health outcomes

Successful ACL reconstruction with a variant of the pes anserinus

An anatomical variant of the pes anserinus encountered during anterior cruciate ligament reconstructive surgery which has not been previously described is discussed. During routine harvesting, the sartorius fascia was incised and the semitendinosus and gracilis tendons were identified. At the distal portion, it was noted that each tendon gave off an additional tendinous slip. The slip from the semitendinosus tendon had attached to the gracilis tendon and vice versa, thereby creating a double pes anserinus. This variant was used to construct the graft, and at 1 year review the patient had returned to full sporting activities with no complications encountered

Clinical and Nutritional Care Pathways of Patients with Malignant Bowel Obstruction: A Retrospective Analysis in a Tertiary UK Center

We describe a retrospective cohort study of patients with malignant bowel obstruction to examine their nutritional care pathways between 1.1.16 and 31.12.16 with readmissions until 31.12.17. Data were analyzed by comparing patients who were referred (R) and not referred (NR) for PN. We identified 72 patients with 117 MBO admissions (mean ± SD age:63.1 ± 13.1yrs, 79% female). 24/72 patients were in R group. Predominant primary malignancies were gynaecological and lower-gastrointestinal cancers (76%). 83% patients had metastases (61% sub-diaphragmatically). All patients were at high-risk of malnutrition and baseline mean weight loss was 7%. Discussion of PN at multidisciplinary team meeting (MDT) (22% vs.5%, P = 0.02) and dietetic contact (94% vs. 41%, P < 0.0001) were more likely to occur in the R group. In 13/69 MBO admissions in NR group, reasons for non-referral were unclear. Median baseline and follow-up weight was similar (55–55.8 kg). Overall survival was 4.7 (1.4–15.2)months, with no differences by referral groups. We compared a sub-sample of patients who ‘may have’ required PN (n = 10) vs. those discharged on home PN (n = 10) and found greater survival in the HPN group (323vs.91 day, P < 0.01). Our findings highlight disparity in care pathways suggesting that nutritional care should be integrated into clinical management discussion(s) at MDT to ensure equal access to nutritional services