Smear positivity in paediatric and adult tuberculosis: systematic review and meta-analysis.

Background: Tuberculosis (TB) diagnosis continues to rely on sputum smear microscopy in many settings. We conducted a meta-analysis to estimate the percentage of children and adults with tuberculosis that are sputum smear positive.

Methods: We searched PubMed, MEDLINE, Embase, and Global Health databases for studies that included both children and adults with all forms of active TB.

Predictive thermodynamics for ionic solids and liquids.

The application of thermodynamics is simple, even if the theory may appear intimidating. We describe tools, developed over recent years, which make it easy to estimate often elusive thermodynamic parameter values, generally (but not exclusively) for ionic materials, both solid and liquid, as well as for their solid hydrates and solvates. The tools are termed volume-based thermodynamics (VBT) and thermodynamic difference rules (TDR), supplemented by the simple salt approximation (SSA) and single-ion values for volume, Vm, heat capacity, , entropy, , formation enthalpy, ΔfH°, and Gibbs formation energy, ΔfG°.

Effectiveness of a novel cellular therapy to treat multidrug-resistant tuberculosis.

Introduction: We urgently need novel treatments for multidrug-resistant tuberculosis (MDR-TB). Autologous mesenchymal stromal cell (MSC) infusion is one such possibility due to its potential to repair damaged lung tissue and boost immune responses. We aimed to assess the effectiveness of MSC to improve outcomes among MDR-TB patients.

The Effect of Oxygen on Bile Resistance in .

is a Gram-positive facultative anaerobe that is the causative agent of the disease listeriosis. The infectious ability of this bacterium is dependent upon resistance to stressors encountered within the gastrointestinal tract, including bile. Previous studies have indicated bile salt hydrolase activity increases under anaerobic conditions, suggesting anaerobic conditions influence stress responses.

Asymmetric Organocatalytic Stepwise [2+2] Entry to Tetra-Substituted Heterodimeric and Homochiral Cyclobutanes.

An asymmetric synthesis of tetra-substituted cyclobutanes involving an organocatalytic, stepwise [2+2]-cycloaddition is described. The secondary-amine-catalyzed method allows for the hetero-dimerization of two different cinnamic-acid-derived sub-units, opening a novel one-step assembly to densely functionalized, head-to-tail coupled dimeric cyclobutanes in high enantiomeric excess. A series of selective synthetic interconversions in these sensitive cycloadducts is also described.

Supramolecular macrocycles reversibly assembled by Te(…)O chalcogen bonding.

Organic molecules with heavy main-group elements frequently form supramolecular links to electron-rich centres. One particular case of such interactions is halogen bonding. Most studies of this phenomenon have been concerned with either dimers or infinitely extended structures (polymers and lattices) but well-defined cyclic structures remain elusive.

Long-Term Outcome Data in Patients following One Year's Use of a Fully Implantable Active Middle Ear Implant.

This study examined the safety and efficacy of a fully implantable active middle ear (AMEI) system. Outcome measures assessed AMEI performance compared with an optimally fitted conventional hearing aid (CHA). Fifty adults with stable, symmetric moderate-to-severe sensorineural hearing loss were implanted at 9 ambulatory settings.

iPSC Neuronal Assay Identifies Amaryllidaceae Pharmacophore with Multiple Effects against Herpesvirus Infections.

The Amaryllidaceae alkaloid trans-dihydrolycoricidine 7 and three analogues 8-10 were produced via asymmetric chemical synthesis. Alkaloid 7 proved superior to acyclovir, the current standard for herpes simplex virus, type 1 (HSV-1) infection. Compound 7 potently inhibited lytic HSV-1 infection, significantly reduced HSV-1 reactivation, and more potently inhibited varicella zoster virus (VZV) lytic infection.

Synthetic, structural, and computational investigations of N-alkyl benzo-2,1,3-selenadiazolium iodides and their supramolecular aggregates.

Despite their versatility, the application of telluradiazoles as supramolecular building blocks is considerably constrained by their sensitivity to moisture. Albeit more robust, their selenium analogues form weaker supramolecular interactions. These, however, are enhanced when one nitrogen atom is bonded to an alkyl group.

Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial.

Background: Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the effect of early detection by screening on ovarian cancer mortality.

Methods: In this randomised controlled trial, we recruited postmenopausal women aged 50-74 years from 13 centres in National Health Service Trusts in England, Wales, and Northern Ireland.

DNA recognition for virus assembly through multiple sequence-independent interactions with a helix-turn-helix motif.

The helix-turn-helix (HTH) motif features frequently in protein DNA-binding assemblies. Viral pac site-targeting small terminase proteins possess an unusual architecture in which the HTH motifs are displayed in a ring, distinct from the classical HTH dimer. Here we investigate how such a circular array of HTH motifs enables specific recognition of the viral genome for initiation of DNA packaging during virus assembly.

Alternate wiring of a KNOXI genetic network underlies differences in leaf development of A. thaliana and C. hirsuta.

Two interrelated problems in biology are understanding the regulatory logic and predictability of morphological evolution. Here, we studied these problems by comparing Arabidopsis thaliana, which has simple leaves, and its relative, Cardamine hirsuta, which has dissected leaves comprising leaflets. By transferring genes between the two species, we provide evidence for an inverse relationship between the pleiotropy of SHOOTMERISTEMLESS (STM) and BREVIPEDICELLUS (BP) homeobox genes and their ability to modify leaf form.

Counting children with tuberculosis: why numbers matter.

In the last 5 years, childhood tuberculosis (TB) has received increasing attention from international organisations, national TB programmes and academics. For the first time, a number of different groups are developing techniques to estimate the burden of childhood TB. We review the challenges in diagnosing TB in children and the reasons why cases in children can go unreported.

Data for action: collection and use of local data to end tuberculosis.

Accelerating progress in the fight against tuberculosis will require a drastic shift from a strategy focused on control to one focused on elimination. Successful disease elimination campaigns are characterised by locally tailored responses that are informed by appropriate data. To develop such a response to tuberculosis, we suggest a three-step process that includes improved collection and use of existing programmatic data, collection of additional data (eg, geographic information, drug resistance, and risk factors) to inform tailored responses, and targeted collection of novel data (eg, sequencing data, targeted surveys, and contact investigations) to improve understanding of tuberculosis transmission dynamics.

Past, present and future of respiratory research: A survey of Canadian health care professionals.

Background: The Canadian Respiratory Health Professionals (CRHP) is the multidisciplinary health care professional group of the Canadian Lung Association. Although the CRHP has a growing number of highly qualified researchers, the landscape of their research in Canada has not been described.

Objectives: To describe the level of respiratory research engagement; identify barriers and facilitators to research engagement; describe the experience and interest in developing research skills; and identify priority areas of future respiratory research among health care professionals.

Cochlear Implant Electrode Effect on Sound Energy Transfer Within the Cochlea During Acoustic Stimulation.

Hypothesis: Cochlear implants (CIs) designed for hearing preservation will not alter mechanical properties of the middle and inner ears as measured by intracochlear pressure (P(IC)) and stapes velocity (Vstap).

Background: CIs designed to provide combined electroacoustic stimulation are now available. To maintain functional acoustic hearing, it is important to know if a CI electrode can alter middle or inner ear mechanics because any alteration could contribute to elevated low-frequency thresholds in electroacoustic stimulation patients.

Synthesis of the cyanobacterial metabolite nostodione A, structural studies and potent antiparasitic activity against Toxoplasma gondii.

A total synthesis of the cyanobacterial natural product nostodione A is reported involving a convergent, diversity-oriented route, enabling the assembly of a mini-library of structural analogues. The first single crystal X-ray structural determination on a member of this series is reported along with SAR studies identifying potent inhibitors of invasion and replication of the parasitic protozoan Toxoplasma gondii.

Understanding patient beliefs regarding the use of imaging in the management of low back pain.

Background: Imaging for low back pain (LBP) remains common despite guidelines recommending against routine imaging. Patient beliefs about imaging may contribute to the problem. This study aimed to quantitatively investigate patient beliefs regarding the need for imaging in managing LBP and to investigate whether personal characteristics, pain characteristics or back pain beliefs are associated with imaging beliefs.

Effects of Skin Thickness on Cochlear Input Signal Using Transcutaneous Bone Conduction Implants.

Hypothesis: Intracochlear sound pressures (PIC) and velocity measurements of the stapes, round window, and promontory (VStap/RW/Prom) will show frequency-dependent attenuation using magnet-based transcutaneous bone conduction implants (TCBCIs) in comparison with direct-connect skin-penetrating implants (DCBCIs).

Background: TCBCIs have recently been introduced as alternatives to DCBCIs. Clinical studies have demonstrated elevated high-frequency thresholds for TCBCIs as compared with DCBCIs; however, little data exist examining the direct effect of skin thickness on the cochlear input signal using TCBCIs.

From bacterial to human dihydrouridine synthase: automated structure determination.

The reduction of uridine to dihydrouridine at specific positions in tRNA is catalysed by dihydrouridine synthase (Dus) enzymes. Increased expression of human dihydrouridine synthase 2 (hDus2) has been linked to pulmonary carcinogenesis, while its knockdown decreased cancer cell line viability, suggesting that it may serve as a valuable target for therapeutic intervention. Here, the X-ray crystal structure of a construct of hDus2 encompassing the catalytic and tRNA-recognition domains (residues 1-340) determined at 1.

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Rising TAK-438 (Vonoprazan) Doses in Healthy Male Japanese/non-Japanese Subjects.

Objectives: To evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-438 (vonoprazan, a potassium-competitive acid blocker) in healthy male subjects.

Methods: In two phase I, randomized, double-blind, placebo-controlled, single rising-dose studies, healthy male subjects (Japan N=84; UK N=63) received a single TAK-438 dose (1-120 mg in Japan and 1-40 mg in the UK). Assessments included safety, tolerability, pharmacokinetics, and pharmacodynamics (intragastric pH).

Global and Regional Burden of Isoniazid-Resistant Tuberculosis.

Background: Isoniazid has been the backbone of tuberculosis chemotherapy for 6 decades. Resistance to isoniazid threatens the efficacy of treatment of tuberculosis disease and infection. To inform policies around treatment of tuberculosis disease and infection in children, we sought to estimate both the proportion of child tuberculosis cases with isoniazid resistance and the number of incident isoniazid-resistant tuberculosis cases in children, by region.

Work-related thumb disorders in South African physiotherapists treating musculoskeletal conditions using manual therapy techniques.

Research Question: What is the prevalence of and factors associated with work-related thumb problems (WRTP) in South African physiotherapists treating musculoskeletal conditions using manual therapy techniques?

Design: A cross-sectional, descriptive study design was used and data were collected using two Internet-based questionnaires.

Participants: The sample size calculated for the study was 284 using 95% confidence levels and a 5% margin of error. There were 395 participants that were included in the study.