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Surgical sperm retrieval (SSR) is currently one of the most common procedures in in vitro fertilization (IVF). However, a gap between the guidelines and routine clinical practice regarding antibiotic use in SSR, which might lead to antibiotic resistance, is a challenging problem worldwide. A cross-sectional survey was conducted from May 1, 2021, to July 15, 2021, to investigate antibiotic usage by medical professionals when performing SSR in IVF centers in Vietnam. The confidential questionnaire comprised 12 items, including characteristics of the study population, awareness of antimicrobial resistance, attitude toward prescribing antibiotics, and current practice of prescribing antibiotics when performing SSR. Surveys were completed by 30 of 45 registered IVF centers (66.7%). Among 67 physicians working at those centers, the age and work-experience years (mean ± standard deviation [s.d.]) were 38.6 ± 6.6 years and 11.2 ± 7.0 years, respectively. Over 60% of them held a degree in Obstetrics and Gynecology, and over four-fifths were men. Most respondents "often/very often/always" raised awareness of antimicrobial resistance to their patients (83.3%), but only half of them "often/occasionally" prescribed antibiotics to patients with SSR in cases where the prescription would be optional. About one-tenth of respondents followed the recommendation from the American Urological Association using "prophylaxis only" for SSR patients. For more invasive SSR, physicians tended to prescribe more complicated and sometimes inappropriate regimens. In conclusion, antibiotic usage in SSR was not always appropriate among IVF centers. Further studies may define specific recommendations for regimens, intervention strategies, and programs to promote appropriate antibiotic use for SSR patients among IVF specialists., Competing Interests: None

A new glycoside, telosmoside A 21 ( 1 ) and two known compounds, telosmoside A 6 ( 2 ) and telosmoside A 1 ( 3 ), were isolated from the roots of Jasminanthes tuyetanhiae . The structure of compound 1 was identified from its spectroscopic data and by comparison with the literature.

Acute hepatopancreatic necrosis disease (AHPND) has recently emerged as a serious disease of cultured shrimp. A total of 19 lactic acid bacteria (LAB) strains isolated from shrimp samples were characterized based on morphological characteristics, biochemical tests, sequencing analysis, and their ability to antagonize Vibrio parahaemolyticus, which causes AHPND in whiteleg shrimp. Results from the agar well diffusion method indicated that 3 out of 19 isolated LAB strains showed the highest antagonizing ability against AHPND V. parahaemolyticus strain with an inhibition zone diameter ranging from 18 to 20 mm. Experiments where shrimps were given feed supplemented with these LAB strains and challenged with AHPND strain showed high survival rates (approximately 80.0%), which were not significantly different as compared to those recorded in the negative control treatment (86.6%), but significantly different to those recorded in the positive control treatment (40.6%) after 16 days of the experiment. However, the histological images of shrimp hepatopancreas indicated that the infection rate significantly reduced from 60.0% to 11.1% in shrimps fed with LAB-supplemented feeds and challenged with AHPND V. parahaemolyticus strain as compared to those in the positive control treatment. A polymerase chain reaction (PCR) and 16S rRNA gene sequencing confirmed the identification of LAB strain. These results can be applied in further experiments to investigate the ability of L. plantarum in preventing AHPND in intensively cultured whiteleg shrimp., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

There is a need for single cell analysis methods that enable the identification and localization of different kinds of biomolecules throughout cells and intact tissues, thereby allowing characterization and classification of individual cells and their relationships to each other within intact systems. Expansion microscopy (ExM) is a technology that physically magnifies tissues in an isotropic way, thereby achieving super-resolution microscopy on diffraction-limited microscopes, enabling rapid image acquisition and large field of view. As a result, ExM is well-positioned to integrate molecular content and cellular morphology, with the spatial precision sufficient to resolve individual biological building blocks, and the scale and accessibility required to deploy over extended 3-D objects like tissues and organs., (© 2018 Federation of European Biochemical Societies.)

Optical and electron microscopy have made tremendous inroads toward understanding the complexity of the brain. However, optical microscopy offers insufficient resolution to reveal subcellular details, and electron microscopy lacks the throughput and molecular contrast to visualize specific molecular constituents over millimeter-scale or larger dimensions. We combined expansion microscopy and lattice light-sheet microscopy to image the nanoscale spatial relationships between proteins across the thickness of the mouse cortex or the entire Drosophila brain. These included synaptic proteins at dendritic spines, myelination along axons, and presynaptic densities at dopaminergic neurons in every fly brain region. The technology should enable statistically rich, large-scale studies of neural development, sexual dimorphism, degree of stereotypy, and structural correlations to behavior or neural activity, all with molecular contrast., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: The post-2015 End TB Strategy proposes targets of 50% reduction in tuberculosis incidence and 75% reduction in mortality from tuberculosis by 2025. We aimed to assess whether these targets are feasible in three high-burden countries with contrasting epidemiology and previous programmatic achievements., Methods: 11 independently developed mathematical models of tuberculosis transmission projected the epidemiological impact of currently available tuberculosis interventions for prevention, diagnosis, and treatment in China, India, and South Africa. Models were calibrated with data on tuberculosis incidence and mortality in 2012. Representatives from national tuberculosis programmes and the advocacy community provided distinct country-specific intervention scenarios, which included screening for symptoms, active case finding, and preventive therapy., Findings: Aggressive scale-up of any single intervention scenario could not achieve the post-2015 End TB Strategy targets in any country. However, the models projected that, in the South Africa national tuberculosis programme scenario, a combination of continuous isoniazid preventive therapy for individuals on antiretroviral therapy, expanded facility-based screening for symptoms of tuberculosis at health centres, and improved tuberculosis care could achieve a 55% reduction in incidence (range 31-62%) and a 72% reduction in mortality (range 64-82%) compared with 2015 levels. For India, and particularly for China, full scale-up of all interventions in tuberculosis-programme performance fell short of the 2025 targets, despite preventing a cumulative 3·4 million cases. The advocacy scenarios illustrated the high impact of detecting and treating latent tuberculosis., Interpretation: Major reductions in tuberculosis burden seem possible with current interventions. However, additional interventions, adapted to country-specific tuberculosis epidemiology and health systems, are needed to reach the post-2015 End TB Strategy targets at country level., Funding: Bill and Melinda Gates Foundation., (Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.)

Background: The post-2015 End TB Strategy sets global targets of reducing tuberculosis incidence by 50% and mortality by 75% by 2025. We aimed to assess resource requirements and cost-effectiveness of strategies to achieve these targets in China, India, and South Africa., Methods: We examined intervention scenarios developed in consultation with country stakeholders, which scaled up existing interventions to high but feasible coverage by 2025. Nine independent modelling groups collaborated to estimate policy outcomes, and we estimated the cost of each scenario by synthesising service use estimates, empirical cost data, and expert opinion on implementation strategies. We estimated health effects (ie, disability-adjusted life-years averted) and resource implications for 2016-35, including patient-incurred costs. To assess resource requirements and cost-effectiveness, we compared scenarios with a base case representing continued current practice., Findings: Incremental tuberculosis service costs differed by scenario and country, and in some cases they more than doubled existing funding needs. In general, expansion of tuberculosis services substantially reduced patient-incurred costs and, in India and China, produced net cost savings for most interventions under a societal perspective. In all three countries, expansion of access to care produced substantial health gains. Compared with current practice and conventional cost-effectiveness thresholds, most intervention approaches seemed highly cost-effective., Interpretation: Expansion of tuberculosis services seems cost-effective for high-burden countries and could generate substantial health and economic benefits for patients, although substantial new funding would be required. Further work to determine the optimal intervention mix for each country is necessary., Funding: Bill & Melinda Gates Foundation., (Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.)

To reach the ambitious WHO TB global targets by 2035, it is likely that China will need a comprehensive strategy that builds on its existing high-quality directly observed treatment, short-course program. This will require optimizing the use of existing tools within a changing health system landscape. In addition, new tools are needed to identify and treat TB in high-risk groups and in older people, who are a growing driver of disease incidence. Lastly, strategies are needed to address the proximate risk factors and social determinants that underlie trends in TB burden., (© The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In the last 20 years, China ramped up a DOTS (directly observed treatment, short-course)-based tuberculosis (TB) control program with 80% population coverage, achieving the 2015 Millennium Development Goal of a 50% reduction in TB prevalence and mortality. Recently, the World Health Organization developed the End TB Strategy, with an overall goal of a 90% reduction in TB incidence and a 95% reduction in TB deaths from 2015-2035. As the TB burden shifts to older individuals and China's overall population ages, it is unclear if maintaining the current DOTS strategy will be sufficient for China to reach the global targets., Methods: We developed an individual-based computational model of TB transmission, implementing realistic age demographics and fitting to country-level data of age-dependent prevalence over time. We explored the trajectory of TB burden if the DOTS strategy is maintained or if new interventions are introduced using currently available and soon-to-be-available tools. These interventions include increasing population coverage of DOTS, reducing time to treatment, increasing treatment success, and active case finding among elders > 65 years old. We also considered preventative therapy in latently infected elders, a strategy limited by resource constraints and the risk of adverse events., Results: Maintenance of the DOTS strategy reduces TB incidence and mortality by 42% (95% credible interval, 27-59%) and 41% (5-64%), respectively, between 2015 and 2035. A combination of all feasible interventions nears the 2035 mortality target, reducing TB incidence and mortality by 59% (50-76%) and 83% (73-94%). Addition of preventative therapy for elders would enable China to nearly reach both the incidence and mortality targets, reducing incidence and mortality by 84% (78-93%) and 92% (86-98%)., Conclusions: The current decline in incidence is driven by two factors: maintaining a low level of new infections in young individuals and the aging out of older latently infected individuals who contribute incidence due to reactivation disease. While further reducing the level of new infections has a modest effect on burden, interventions that limit reactivation have a greater impact on TB burden. Tools that make preventative therapy more feasible on a large scale and in elders will help China achieve the global targets.

Background: A pre-erythrocytic vaccine could provide a useful tool for burden reduction and eventual eradication of malaria. Mathematical malaria models provide a mechanism for evaluating the effective burden reduction across a range of transmission conditions where such a vaccine might be deployed., Methods: The EMOD model is an individual-based model of malaria transmission dynamics, including vector lifecycles and species-specific behaviour, coupled to a mechanistic intrahost model of malaria parasite and host immune system dynamics. The present work describes the extension of the EMOD model to include diagnoses of severe malaria and iterative calibration of the immune system parameters and parasite antigenic variation to age-stratified prevalence, incidence and severe disease incidence data obtained from multiple regions with broadly varying transmission conditions in Africa. An ensemble of calibrated model parameter sets is then employed to evaluate the potential impact of routine immunization with a pre-erythrocytic vaccine., Results: The reduction in severe malaria burden exhibits a broad peak at moderate transmission conditions. Under sufficiently intense transmission, a vaccine that reduces but does not eliminate the probability of acquisition from a single challenge bite may delay infections but produces minimal or no net reduction. Conversely, under sufficiently weak transmission conditions, a vaccine can provide a high fractional reduction but avert a relatively low absolute number of cases due to low baseline burden., Conclusions: Roll-out of routine immunization with pre-erythrocytic malaria vaccines can provide substantial burden reduction across a range of transmission conditions typical to many regions in Africa.

In this work, we use coarse-grained modeling to study the free solution electrophoretic mobility of small highly charged peptides (lysine, arginine, and short oligos thereof (up to nonapeptides)) in NaCl and Na2SO4 aqueous solutions at neutral pH and room temperature. The experimental data are taken from the literature. A bead modeling methodology that treats the electrostatics at the level of the nonlinear Poisson Boltzmann equation developed previously in our laboratory is able to account for the mobility of all peptides in NaCl, but not Na2SO4. The peptide mobilities in Na2SO4 can be accounted for by including sulfate binding in the model and this is proposed as one possible explanation for the discrepancy. Oligo arginine peptides bind more sulfate than oligo lysines and sulfate binding increases with the oligo length., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This prospective cohort study examined the effects of atosiban on uterine contraction, implantation rate (IR) and clinical pregnancy rate (CPR) in women undergoing IVF/embryo transfer. The study enrolled 71 women with repeated implantation failure (RIF; no pregnancies from an average of 4.8 previous embryo transfers with a mean of 12 top-quality embryos) undergoing IVF/embryo transfer using cryopreserved embryos. The total atosiban dose was 36.75 mg. The IR per transfer and CPR per cycle were 13.9% and 43.7%, respectively. Before atosiban, 14% of subjects had a high frequency of uterine contractions (≥ 16 in 4 min). The frequency of uterine contractions was reduced after atosiban. This reduction of uterine contractions in all cycles was significant overall (from 6.0 to 2.6/4 min; P<0.01), in cycles with ≥ 16 uterine contractions/4 min at baseline (from 18.8 to 5.1; P<0.01) and in cycles with <16 uterine contractions/4 min (from 3.9 to 2.2; P<0.01). IR and CPR improved in all subjects, irrespective of baseline uterine contraction frequency. This is the first prospective study showing that atosiban may benefit subjects with RIF undergoing IVF/embryo transfer with cryopreserved embryos. One potential mechanism is the reduction in uterine contractility, but others may also contribute. Many women undergoing IVF/embryo transfer do not achieve the outcome that they wish for. In fact, IVF/embryo transfer repeatedly fails for a subgroup of patients. There are limited options available to help these patients with repeat implantation failure (RIF) to become pregnant. This study looks at one potential new treatment option for women who experience RIF. A drug called atosiban is already being used to delay premature labour by inhibiting contractions of the uterus. In this study, atosiban was given at the time of embryo transfer to women undergoing IVF/embryo transfer. Atosiban reduced the number of uterine contractions in these patients and also increased the implantation and pregnancy rates. The pregnancy rate went from zero to 43.7%. The beneficial effects of atosiban were observed not only in patients who had a high frequency of uterine contractions at baseline but also in those who had a low frequency. These findings suggest that atosiban may have other benefits in addition to its effect on contractions of the uterus. More studies are required to find out exactly how atosiban works and to increase the knowledge of its use in patients with RIF undergoing IVF/embryo transfer., (Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Delivery of drugs and macromolecules into the brain is a challenging problem, due in part to the blood-brain barrier. In this article, we focus on the possibilities and limitations of two infusion techniques devised to bypass the blood-brain barrier: convection enhanced delivery (CED) and retro-convection enhanced delivery (R-CED). CED infuses fluid directly into the interstitial space of brain or tumor, whereas R-CED removes fluid from the interstitial space, which results in the transfer of drugs from the vascular compartment into the brain or tumor. Both techniques have shown promising results for the delivery of drugs into large volumes of tissue. Theoretical approaches of varying complexity have been developed to better understand and predict brain interstitial pressures and drug distribution for these techniques. These theoretical models of flow and diffusion can only be solved explicitly in simple geometries, and spherical symmetry is usually assumed for CED, while axial symmetry has been assumed for R-CED. This perspective summarizes features of these models and provides physical arguments and numerical simulations to support the notion that spherical symmetry is a reasonable approximation for modeling CED and R-CED. We also explore the potential of multi-catheter arrays for delivering and compartmentalizing drugs using CED and R-CED.

A retro-convection enhanced delivery (R-CED) method has been developed to improve the entry of intravenously administered therapeutics within solid brain tumors. R-CED uses an osmotic gradient to withdraw brain interstitial fluid (ISF) in a controlled manner via an implanted microdialysis catheter. Withdrawal of ISF increases the local tissue specific gravity in normal brain and increases twofold the extravasation of intravenous Evans blue (EB) albumin in normal brain and in an orthotopic 9L tumor. R-CED also increases the extravasation of 70 nm fluorescent liposomes fivefold in the 9L tumor. Thus the transmembrane osmotic gradient induces movement of substances in the blood into the tissue parenchyma. Following probe removal, the magnitude of the R-CED effect on EB-albumin extravasation decreases to control values within 1.5 h in normal brain; however, the effect persists beyond 6 h in the tumor. There was no evidence of histologic damage to the neurons at either 6 h or 2 weeks after R-CED. These studies establish the feasibility of applying R-CED to increase the distribution of systemically administered drugs in both the normal tissue-tumor margin as well as in the central tumor core, holding forth the possibility of improved antitumor drug efficacy.

Brain tumor patients face a poor prognosis despite significant advances in tumor imaging, neurosurgery and radiation therapy. Potent chemotherapeutic drugs fail when used to treat brain tumors because biochemical and physiological barriers limit drug delivery into the brain. In the past decade a number of strategies have been introduced to increase drug delivery into the brain parenchyma. In particular, direct drug administration into the brain tumor has shown promising results in both animal models and clinical trials. This technique is well suited for the delivery of liposome and polymer drug carriers, which have the potential to provide a sustained level of drug and to reach cellular targets with improved specificity. We will discuss the current approaches that have been used to increase drug delivery into the brain parenchyma in the context of fluid and solute transport into, through and from the brain, with a focus on liposome and polymer drug carriers.