Combining quality improvement and critical care training: Evaluating an ICU CPR training programme quality improvement initiative at the National Hospital in Tanzania.

Background: The United Republic of Tanzania has had a 41.4% mortality rate in the intensive care unit. In Tanzania, the Ministry of Health and Social Welfare has implemented quality improvement (QI), yet the Tanzanian health sector continues to face resource constraints, unsustainable projects and gaps in knowledge and skills, contributing to unacceptably high mortality rates for Tanzanian patients.

Yield of family screening in dilated cardiomyopathy within low-income setting: Tanzanian experience.

Background: Dilated cardiomyopathy (DCM) is often familial and screening of relatives is recommended. However, studies on the yield of screening are scarce in developing countries.

Aim: The aim of the study was to identify and characterise First-degree relatives of patients with DCM in Tanzania.

Yeast Stn1 promotes MCM to circumvent Rad53 control of the S phase checkpoint.

Treating yeast cells with the replication inhibitor hydroxyurea activates the S phase checkpoint kinase Rad53, eliciting responses that block DNA replication origin firing, stabilize replication forks, and prevent premature extension of the mitotic spindle. We previously found overproduction of Stn1, a subunit of the telomere-binding Cdc13-Stn1-Ten1 complex, circumvents Rad53 checkpoint functions in hydroxyurea, inducing late origin firing and premature spindle extension even though Rad53 is activated normally. Here, we show Stn1 overproduction acts through remarkably similar pathways compared to loss of RAD53, converging on the MCM complex that initiates origin firing and forms the catalytic core of the replicative DNA helicase.

An Evaluation of the Use of Corticosteroids for the Management of Immune-Mediated Adverse Events in Cancer Patients Treated With Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) have gained prominence for the treatment of a variety of malignancies. However, they are associated with the development of immune-mediated adverse events (IMAEs). Appropriate management of IMAEs and subsequent rechallenging of patients with ICI therapy remains an important area of research.

Inhibition of spindle extension through the yeast S phase checkpoint is coupled to replication fork stability and the integrity of centromeric DNA.

Budding yeast treated with hydroxyurea (HU) activate the S phase checkpoint kinase Rad53, which prevents DNA replication forks from undergoing aberrant structural transitions and nuclease processing. Rad53 is also required to prevent premature extension of the mitotic spindle that assembles during a HU-extended S phase. Here we present evidence that checkpoint restraint of spindle extension is directly coupled to Rad53 control of replication fork stability.

Daily fruit and vegetable consumption and diabetes status in middle-aged females in the general US population.

Objectives: Fruit and vegetable consumption may impact development of diabetes, but limited research has addressed whether daily consumption of fruits and vegetables differs by those with and without diabetes, especially within high-risk groups. Thus, the purpose of this study was to determine whether daily fruit and vegetable consumption differs by diabetes status in middle-aged females in the general US population.

Methods: This cross-sectional analysis used 2017 Behavioral Risk Factor Surveillance System data for females ages 45-64 years old in Arizona (n = 2609), Florida (n = 3768), Georgia (n = 1018), and Texas (n = 2092).

Potential Obstacles in the Acquisition of Oral Anticancer Medications.

Purpose: To determine the amount of time elapsed between prescriber order and patient receiving oral anticancer medication.

Patients And Methods: Adult patients with a diagnosis of cancer were prospectively identified in three outpatient oncology clinics when oral anticancer agents were prescribed during a 4-month observation period. For each patient, time to obtain medication was analyzed by the following time points: date of prescription, date of submission to insurance, date prior authorization was obtained, date financial assistance was received, date prescription was processed by pharmacy, and date patient received medication.

Defining the impact of the use of granulocyte colony stimulating factors on the incidence of chemotherapy-induced neutropenia in patients with gynecologic malignancies.

Purpose The objectives of this study were to characterize the incidence of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) with specific chemotherapy agents commonly used in the treatment of gynecologic malignancies, as well as defining the impact of granulocyte colony stimulating factors (G-CSF) on the prevention of CIN and FN in this patient population. Methods This retrospective analysis was conducted from a database of 635 gynecologic cancer patients who received chemotherapy between 1 September 2007 and 31 August 2008. A logistic regression analysis was conducted to determine the impact of potential covariates on the overall incidence of CIN.

Evaluating the potential effect on fetal tissue after exposure to granisetron during pregnancy.

The objective of this study was to elucidate the possible toxic effects on the fetal tissues after exposure to two clinically relevant concentrations of granisetron. Primary cells were isolated from human fetal organs of 16-19 weeks gestational age and treated with 3 ng/mL or 30 ng/mL of granisetron. Cell cycle progression was evaluated by flow cytometry.

Evaluation of the maternal-fetal transfer of granisetron in an ex vivo placenta perfusion model.

The objective of this study was to estimate maternal-fetal transplacental passage of granisetron in an ex vivo placental perfusion model. Term human placentas (N=8) were collected immediately after delivery. A single cotyledon from each placenta was perfused granisetron concentration to mimic systemic maternal peak plasma concentrations following either IV (50ng/mL) or transdermal administration (5ng/mL).

Evaluation of pegylated liposomal doxorubicin dose on the adverse drug event profile and outcomes in treatment of recurrent endometrial cancer.

Objective: This study aims to determine factors that may increase the likelihood of adverse drug events (ADEs) in patients with recurrent endometrial cancer treated with pegylated liposomal doxorubicin (PLD) as well as this agent's impact on clinical outcomes.

Methods: The treatment records of patients with endometrial cancer who received PLD at The University of Texas, MD Anderson Cancer Center, from 1996 to 2006 were reviewed. Patient demographics, PLD dose, ADEs, use of supportive care interventions, disease progression, and survival were extracted.

Defining the role of echinocandin catechol functional groups in the development of secondary hepatocellular carcinoma.

Objectives: To determine whether the catechol functional group on echinocandins decreases the catechol-O-methyltransferase (COMT) metabolism of catechol oestrogens (CEs) and the potential role of this functional group in the development of hepatocellular cancer.

Methods: Human COMT expression was measured by RT-PCR in a panel of selected human cancer cell lines and human hepatocytes. An ex vivo human hepatocyte model was employed to evaluate the metabolism of 17-β-oestradiol to CEs in the presence of a catechol (B(0)C) versus a non-catechol echinocandin (B(0)) compound.

Clinical perspectives on the role of the human papillomavirus vaccine in the prevention of cancer.

The role of human papillomavirus (HPV) in the genesis of cervical cancer has been well documented, and an increasing body of literature exists with regard to the role of HPV in other cancers, including cancers of the head and neck. With the recent expansion of the United States Food and Drug Administration's approval of the quadrivalent HPV virus-like particle vaccine to include men and boys and approval of the bivalent vaccine this year, the controversies regarding who should be vaccinated, at what age is vaccination most appropriate, and the limitations of the available HPV vaccines are increasing. Health care providers are challenged with evaluating the current, but continually changing, clinical evidence when making critical decisions for their patients.

The yeast SUMO isopeptidase Smt4/Ulp2 and the polo kinase Cdc5 act in an opposing fashion to regulate sumoylation in mitosis and cohesion at centromeres.

Post-translation modification through the SUMO pathway is cell cycle regulated, with specific SUMO conjugates accumulating in mitotic cells. The basis for this regulation, however, and its functional significance remain poorly understood. We present evidence that in budding yeast sumoylation during mitosis may be controlled through the SUMO deconjugating enzyme Smt4/Ulp2.

Synthesis and pharmacological evaluation of 1,2,3,4-tetrahydropyrazino[1,2-a]indole and 2-[(phenylmethylamino)methyl]-1H-indole analogues as novel melatoninergic ligands.

Two novel series of melatonin-derived compounds have been synthesized and pharmacologically evaluated at the MT(1) and MT(2) subtypes of melatonin receptors. Compounds 12b-c are non-selective high-affinity MT(1) and MT(2) receptor ligands (K(i)=7-11 nM). Compound 12b had little intrinsic activity at the MT(1) receptor and no intrinsic activity at the MT(2) receptor.

2-[(2,3-dihydro-1H-indol-1-yl)methyl]melatonin analogues: a novel class of MT2-selective melatonin receptor antagonists.

A novel series of 2-[(2,3-dihydro-1H-indol-1-yl)methyl]melatonin analogues has been prepared to probe the steric and electronic properties of the binding pocket of the MT(2) receptor accommodating the "out-of-plane" substituent of MT(2)-selective antagonists. The acetamide (6b) bearing an usubstituted indoline moiety displayed an excellent binding affinity and selectivity toward the MT(2)-subtype (MT(2), K(i) = 1 nM; MT(1), K(i) = 115 nM), behaving as a competitive antagonist. 5-Me, 5-OMe, 5-Br, 6-NH(2), and 6-NO(2) substitution of the indoline moiety reduced both MT(2) affinity and selectivity, indicating that hydrophobic interactions play a decisive role in binding the out-of-plane substituent.

Yeast telomere capping protein Stn1 overrides DNA replication control through the S phase checkpoint.

Telomere integrity is maintained through end-protection proteins that block nuclease degradation and prevent telomeres from being recognized as DNA breaks. Although less well understood, end protection proteins may also play a role in facilitating telomere replication. Here, we show that overproduction (OP) of the yeast telomere capping protein Stn1 makes cells highly sensitive to the replication inhibitors hydroxyurea (HU) and methyl-methane sulfonate (MMS).

Decrease of Visual Fields Due to Re-growth of a Big Aneurysm after Coiling. A case report.

We report the case of a 50-year-old man with the chief complaint of narrowing of the visual fields and blurring in his right eye. He had undergone coiling for bilateral aneurysms of the ophthalmic segment of the internal carotid arteries 15 months previously. Angiography showed re-growth of the left ophthalmic aneurysm.

Synthesis and pharmacological evaluation of pentacyclic 6a,7-dihydrodiindole and 2,3-dihydrodiindole derivatives as novel melatoninergic ligands.

The synthesis of novel melatonin analogues 3a and 4a-c designed as melatonin receptor ligands is described. Among the newly synthesized ligands, 2-((S)-2-hydroxymethylindolin-1-ylmethyl)-melatonin 4b displayed the highest affinity for MT(1) receptors (K(i)=9.8 nM) and for MT(2) subtype (K(i)=7.

One step construction of PCR mutagenized libraries for genetic analysis by recombination cloning.

Recombination cloning encompasses a set of technologies that transfer gene sequences between vectors through site-specific recombination. Due in part to the instability of linear DNA in bacteria, both the initial capture and subsequent transfer of gene sequences is often performed using purified recombination enzymes. However, we find linear DNAs flanked by loxP sites recombine efficiently in bacteria expressing Cre recombinase and the lambda Gam protein, suggesting Cre/lox recombination of linear substrates can be performed in vivo.

Synthesis, NMR conformational analysis and pharmacological evaluation of 7,7a,13,14-tetrahydro-6H-cyclobuta[b]pyrimido[1,2-a:3,4-a']diindole analogues as melatonin receptor ligands.

A structure for the self-condensation product of 2-(1H-indol-2-yl)ethyl tosylate 2a, previously proposed as 6,7,14,15-tetrahydro-15aH-azocino[1,2-a:6,5-b]diindole 3a, was revised based on the (13)C-2D-INADEQUATE experiment, and proved to be 7,7a,13,14-tetrahydro-6H-cyclobuta[b]pyrimido[1,2-a:3,4-a']diindole 4a. A mechanism for the unexpected formation of this novel hexacyclic heterocycle was proposed and its NMR solution structure was elucidated. Five derivatives of the title ring skeleton 12-16 designed as melatonin receptor ligands were synthesized and their affinities for the human MT(1) and MT(2) receptors were determined.

Growth hormone stimulation test results as predictors of recombinant human growth hormone treatment outcomes: preliminary analysis of the national cooperative growth study database.

Growth hormone (GH) stimulation tests are considered a prerequisite to clinical trials of recombinant human GH (rhGH) therapy, but the test results may not be predictive of the treatment outcomes with rhGH. We examined the GH stimulation test results as a predictor of the treatment outcome in a cohort of prepubertal subjects in the National Cooperative Growth Study. A standard is proposed in which a diagnosis of GH deficiency is considered appropriate when a patient has significant first-year catch-up growth and that a positive stimulation test result predicts this outcome.

Combined use of growth hormone and gonadotropin-releasing hormone analogues: the national cooperative growth study experience.

Gonadotropin-releasing hormone ana-logues (GnRHa) are used to treat central precocious puberty. They also are used to delay puberty in short children with a prognosis for impaired adult height. In both cases, growth hormone (GH) treatment is sometimes added.

Patterns of medical practice in cystic fibrosis: part II. Use of therapies. Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis.

This report describes the prescribing pattern of therapeutic interventions in the management of patients with cystic fibrosis (CF), as observed in the Epidemiologic Study of Cystic Fibrosis (ESCF). Use of 20 therapies by 12,622 patients was recorded from each health care encounter (53,024 outpatient visits and 8,561 hospitalizations) during a 1-year period (1995), and analyzed by gender, age, severity of lung disease, and presence of any Pseudomonas species in the respiratory tract. The percentage of patients using the following pulmonary therapies was observed (in descending order): airway clearance techniques (88.