Malnutrition Predicts Clinical Outcome in Patients with Neuroendocrine Neoplasia.

Malnutrition is a common problem in oncological diseases, influencing treatment outcomes, treatment complications, quality of life and survival. The potential role of malnutrition has not yet been studied systematically in neuroendocrine neoplasms (NEN), which, due to their growing prevalence and additional therapeutic options, provide an increasing clinical challenge to diagnosis and management. The aim of this cross-sectional observational study, which included a long-term follow-up, was therefore to define the prevalence of malnutrition in 203 patients with NEN using various methodological approaches, and to analyse the short- and long-term outcome of malnourished patients.

European Crohn's and Colitis Organisation Topical Review on IBD in the Elderly.

This ECCO topical review of the European Crohn's and Colitis Organisation [ECCO] focuses on the epidemiology, pathophysiology, diagnosis, management and outcome of the two most common forms of inflammatory bowel disease, Crohn's disease and ulcerative colitis, in elderly patients. The objective was to reach expert consensus to provide evidence-based guidance for clinical practice.

Mechanisms of first-line antimicrobial resistance in multi-drug and extensively drug resistant strains of Mycobacterium tuberculosis in KwaZulu-Natal, South Africa.

Background: In South Africa, drug resistant tuberculosis is a major public health crisis in the face of the colossal HIV pandemic.

Methods: In an attempt to understand the distribution of drug resistance in our setting, we analysed the rpoB, katG, inhA, pncA and embB genes associated with resistance to key drugs used in the treatment of tuberculosis in clinical isolates of Mycobacterium tuberculosis in the KwaZulu-Natal province.

Results: Classical mutations were detected in the katG, inhA and embB genes associated with resistance to isoniazid and ethambutol.

Fecal Microbiota Transplant in Patients With Recurrent Clostridium Difficile Infection.

Background: The clinical effectiveness of fecal microbiota transplant (FMT) for the treatment of recurrent Clostridium difficile infections (rCDI) has been demonstrated in randomized controlled trials. To assess the current status of FMT in Germany with respect to active centers, local standards, clinical effectiveness and safety, the MicroTrans Registry (NCT02681068) was established.

Methods: In a long-term retrospective multicenter observational study by the German Clinical Microbiome Study Group (GCMSG), primary and secondary cure on day 30 and 90, as well as occurrence of treatment-related adverse events were assessed.

Acute and Long-Term Cardiovascular Effects of Stimulant, Guanfacine, and Combination Therapy for Attention-Deficit/Hyperactivity Disorder.

Objectives: This study examines cardiovascular (CV) effects of guanfacine immediate-release (GUAN-IR), dexmethylphenidate extended-release (DMPH), and their combination (COMB) during acute and long-term treatment of youth with attention-deficit/hyperactivity disorder.

Methods: Two hundred seven participants aged 7-14 years enrolled in an 8-week double-blind randomized trial of GUAN-IR (1-3 milligrams (mg)/day), DMPH (5-20 mg/day), or COMB with fixed-flexible dosing and titrated to optimal behavioral response. Heart rate, systolic blood pressure (BP), diastolic BP, and electrocardiograms were assessed at baseline, end of blinded optimization, and over a 1-year open-label maintenance phase.

Effects of d-Methylphenidate, Guanfacine, and Their Combination on Electroencephalogram Resting State Spectral Power in Attention-Deficit/Hyperactivity Disorder.

Objective: Psychostimulant medications are the gold standard of treatment for attention-deficit/hyperactivity disorder (ADHD); however, a significant minority (∼30%) of individuals with ADHD fail to respond favorably. Noradrenergic agents are increasingly used as ADHD monotherapies or adjuncts for suboptimal stimulant response, yet knowledge of their cortical effects is limited. This study is the first to examine comparative effects of guanfacine (an α adrenergic 2A agonist), psychostimulant, and their combination on resting state cortical activity in ADHD.

Cognitive Effects of Stimulant, Guanfacine, and Combined Treatment in Child and Adolescent Attention-Deficit/Hyperactivity Disorder.

Objective: Psychostimulants are partially effective in reducing cognitive dysfunction associated with attention-deficit/hyperactivity disorder (ADHD). Cognitive effects of guanfacine, an alternative treatment, are poorly understood. Given its distinct action on α2A receptors, guanfacine may have different or complementary effects relative to stimulants.

Combined Stimulant and Guanfacine Administration in Attention-Deficit/Hyperactivity Disorder: A Controlled, Comparative Study.

Objective: Because models of attention-deficit/hyperactivity disorder (ADHD) therapeutics emphasize benefits of both enhanced dopaminergic and noradrenergic signaling, strategies to enhance D1 and α2A agonism may yield enhanced clinical and cognitive responses. This study tested the hypothesis that combined effects of a dopamine and noradrenergic agonist, d-methylphenidate extended-release (DMPH) with guanfacine (GUAN), an α2A receptor agonist, would be clinically superior to either monotherapy and would have equal tolerability.

Method: An 8-week, double-blind, 3-arm, comparative trial randomized 7- to 14-year-olds with DSM-IV ADHD to GUAN (1-3 mg/day), DMPH (5-20 mg/day), or a combination (COMB) with fixed-flexible dosing.

Early Monitoring of Response (MORE) to Golimumab Therapy Based on Fecal Calprotectin and Trough Serum Levels in Patients With Ulcerative Colitis: A Multicenter Prospective Study.

Background: The treatment of ulcerative colitis (UC) patients with moderate to severe inflammatory activity with anti-tumor necrosis factor alpha (TNFα) antibodies leads to a clinical remission rate of 10% after 8 weeks of therapy. However, it must be taken into account that patient selection in clinical trials clearly influences both response and remission rates. An unsatisfactory response to anti-TNFα medication after week 12 often leads to a discontinuation of treatment.

Characterization of the Plasmodium falciparum and P. berghei glycerol 3-phosphate acyltransferase involved in FASII fatty acid utilization in the malaria parasite apicoplast.

Malaria parasites can synthesize fatty acids via a type II fatty acid synthesis (FASII) pathway located in their apicoplast. The FASII pathway has been pursued as an anti-malarial drug target, but surprisingly little is known about its role in lipid metabolism. Here we characterize the apicoplast glycerol 3-phosphate acyltransferase that acts immediately downstream of FASII in human (Plasmodium falciparum) and rodent (Plasmodium berghei) malaria parasites and investigate how this enzyme contributes to incorporating FASII fatty acids into precursors for membrane lipid synthesis.

EMR documentation of physician-patient communication following genomic counseling for actionable complex disease and pharmacogenomic results.

Genomic risk information for potentially actionable complex diseases and pharmacogenomics communicated through genomic counseling (GC) may motivate physicians and patients to take preventive actions. The Ohio State University-Coriell Personalized Medicine Collaborative is a randomized trial to measure the effects of in-person GC on chronic disease patients provided with multiplex results. Nine personalized genomic risk reports were provided to patients through a web portal, and to physicians via electronic medical record (EMR).

Parasites resistant to the antimalarial atovaquone fail to transmit by mosquitoes.

Drug resistance compromises control of malaria. Here, we show that resistance to a commonly used antimalarial medication, atovaquone, is apparently unable to spread. Atovaquone pressure selects parasites with mutations in cytochrome b, a respiratory protein with low but essential activity in the mammalian blood phase of the parasite life cycle.

Gender differences in giant cell arteritis: a case-control study.

Objectives: To determine sex differences in the clinical spectrum and disease pattern of cranial and extracranial giant cell arteritis (GCA).

Methods: Data on 153 consecutive patients with a confirmed diagnosis of GCA between 2002 and 2013 were retrospectively obtained from our database. For every male patient, two age-matched female patients were identified.

Strains of Mycobacterium tuberculosis differ in affinity for human osteoblasts and alveolar cells in vitro.

Although the lung is the primary site of infection of tuberculosis, Mycobacterium tuberculosis is capable of causing infection at other sites. In 5-10 % such extra-pulmonary tuberculosis is located in bone tissue of the spine. It is unknown whether host or microbial factors are responsible for the site where extra-pulmonary tuberculosis manifests itself.

Treatment satisfaction, preferences and perception gaps between patients and physicians in the ulcerative colitis CARES study: A real world-based study.

Background: Ulcerative colitis (UC) is a life time disease and issues with therapy may impact on patient satisfaction and treatment preferences.

Aims: To assess disease and treatment perception gaps from patients' and physicians' perspectives in UC patients.

Methods: Adult patients with moderate-to-severe UC (Mayo score ≥6) naïve to biologic therapy were enrolled in a European, observational, cross-sectional, retrospective study.

Burden of disease and patient-reported outcomes in patients with moderate to severe ulcerative colitis in the last 12 months - Multicenter European cohort study.

Background: Treatment of ulcerative colitis (UC) is aimed at maintaining corticosteroid-free remission and improving quality of life (QoL).

Aim: Assess patients' perception of disease burden and unmet clinical needs in moderate/severe UC patients.

Methods: Adults surgery-free conventionally treated patients with Mayo score ≥6 were enrolled in an observational, cross-sectional, retrospective study in 11 European countries.

Cost-effectiveness of conservation payment schemes for species with different range sizes.

Payments to compensate landowners for carrying out costly land-use measures that benefit endangered biodiversity have become an important policy instrument. When designing such payments, it is important to take into account that spatially connected habitats are more valuable for many species than isolated ones. One way to incentivize provision of connected habitats is to offer landowners an agglomeration bonus, that is, a bonus on top of payments they are receiving to conserve land if the land is spatially connected.

Comparative glaucomatous diagnosis using macular optical coherence tomography and perimetry with centrally condensed stimuli: English version.

The presentation and measurement of the internal retinal layers by current optical coherence tomography (OCT) instruments allow a precise topographic localization of macular glaucomatous damage. Ganglion cell analysis in particular can reveal slight central defects and can effectively be correlated with perimetric strategies with centrally condensed stimuli, so that small glaucomatous defects can be confirmed earlier and more confidently. Progression can also be verified in the early stages of the disease as enlargement and deepening of small localized defects.

A Survey of the ATP-Binding Cassette (ABC) Gene Superfamily in the Salmon Louse (Lepeophtheirus salmonis).

Salmon lice, Lepeophtheirus salmonis (Krøyer, 1837), are fish ectoparasites causing significant economic damage in the mariculture of Atlantic salmon, Salmo salar Linnaeus, 1758. The control of L. salmonis at fish farms relies to a large extent on treatment with anti-parasitic drugs.

Mixture toxicity effects of sea louse control agents in Daphnia magna.

Caligid sea lice are ectoparasites causing major disease problems in industrial salmon farming. Sea louse control currently relies widely on parasiticides. Among non-target species, crustaceans are particularly susceptible to salmon delousing agents.

SCN5A variant that blocks fibroblast growth factor homologous factor regulation causes human arrhythmia.

Nav channels are essential for metazoan membrane depolarization, and Nav channel dysfunction is directly linked with epilepsy, ataxia, pain, arrhythmia, myotonia, and irritable bowel syndrome. Human Nav channelopathies are primarily caused by variants that directly affect Nav channel permeability or gating. However, a new class of human Nav channelopathies has emerged based on channel variants that alter regulation by intracellular signaling or cytoskeletal proteins.

The Plasmodium translocon of exported proteins component EXP2 is critical for establishing a patent malaria infection in mice.

Export of most malaria proteins into the erythrocyte cytosol requires the Plasmodium translocon of exported proteins (PTEX) and a cleavable Plasmodium export element (PEXEL). In contrast, the contribution of PTEX in the liver stages and export of liver stage proteins is unknown. Here, using the FLP/FRT conditional mutatagenesis system, we generate transgenic Plasmodium berghei parasites deficient in EXP2, the putative pore-forming component of PTEX.

Phenotypic Diversity as a Mechanism to Exit Cellular Dormancy.

Microorganisms can facilitate their survival in stressful environments by entering a state of metabolic inactivity or dormancy. However, this state impairs the function of the very sensory systems necessary to detect favorable growth conditions. Thus, how can a metabolically quiescent cell accurately monitor environmental conditions in order to best decide when to exit dormancy? One strategy employed by microbes to deal with changing environments is the generation of phenotypes that may be less well adapted to a current condition but might confer an advantage in the future.