Ventilator-associated pneumonia in patients with cancer: Impact of multidrug resistant bacteria.
Patients with cancer have several risk factors for developing respiratory failure requiring mechanical ventilation (MV). The emergence of multidrug resistant bacteria (MDRB) has become a public health problem, creating a new burden on medical care in hospitals, particularly for patients admitted to the intensive care unit (ICU). To describe risk factors for ventilator-acquired pneumonia (VAP) in patients with cancer and to evaluate the impact of MDRB. A retrospective study was performed from January 2016 to December 2018 at a cancer referral center in Mexico City, which included all patients who were admitted to the ICU and required MV ≥ 48 h. They were classified as those who developed VAP versus those who did not; pathogens isolated, including MDRB. Clinical evolution at 60-d was assessed. Descriptive analysis was carried out; comparison was performed between VAP vs non-VAP and MDRB vs non-MDRB. Two hundred sixty-three patients were included in the study; mean age was 51.9 years; 52.1% were male; 68.4% had solid tumors. There were 32 episodes of VAP with a rate of 12.2%; 11.5 episodes/1000 ventilation-days. The most frequent bacteria isolated were the following: Klebsiella spp. [n = 9, four were Extended-Spectrum Beta-Lactamase (ESBL) producers, one was Carbapenem-resistant (CR)]; Escherichia coli (n = 5, one was ESBL), and Pseudomonas aeruginosa (n = 8, two were CR). One Methicillin-susceptible Staphylococcus aureus was identified. In multivariate analysis, the sole risk factor associated for VAP was length of ICU stay (OR = 1.1; 95%CI: 1.03-1.17; P = 0.003). Sixty-day mortality was 53% in VAP and 43% without VAP (P = 0.342). There was not higher mortality in those patients with MDRB. This study highlights the high percentage of Gram-negative bacteria, which allows the initiation of empiric antibiotic coverage for these pathogens. In this retrospective, single center, observational study, MDRB VAP was not directly linked to increased mortality at 60 days.


Medic One Pediatric (MOPed) cards: standardising paramedic paediatric resuscitation.
Paediatric resuscitation is highly stressful, technically challenging and infrequently performed by paramedics. Length-based equipment selection, weight-based medication dosing and less familiar paediatric clinical scenarios create high cognitive load. Our project aimed to decrease cognitive load and increase paramedic comfort by providing standardised paediatric resuscitation cards across an entire Emergency Medical Services (EMS) system. After 2 years of collaboration between EMS and regional paediatric subspecialists, we created and implemented a novel set of length-based, colour-coded cards: Medic One Pediatric (MOPed) cards. MOPed cards standardise the approach to paediatric scenarios, such as rapid sequence intubation (RSI), seizure management and cardiac arrest. We standardised drug concentrations across all five EMS agencies to allow for volume-based dosing, removing medication calculations, simplifying the process of medication administration and potentially decreasing both calculation error and time to intervention. We consolidated medications on MOPed cards to the 12 most commonly used in Paediatric Advanced Life Support scenarios. We surveyed 240 EMS personnel before and after implementation to determine use and effect on paramedic comfort. After 12 months of implementation, 97% of respondents reported using the new cards as their primary reference, and 94% reported improved speed and accuracy of medication administration. Specifically, RSI medication administration received the greatest improvement in comfort (p=0.001). Additionally, paramedics increased the use of MOPed cards when selecting endotracheal tubes: 45% of the respondents had done so by 6 months, and 60% had done so after 12 months of implementation (p=0.01). MOPed cards were well adopted across a large EMS system, with improvement in paramedic comfort in managing some paediatric resuscitation scenarios.


Deficiency of ribosomal proteins reshapes the transcriptional and translational landscape in human cells.
Human ribosomes have long been thought to be uniform factories with little regulatory function. Accumulating evidence emphasizes the heterogeneity of ribosomal protein (RP) expression in specific cellular functions and development. However, a systematic understanding of functional relevance of RPs is lacking. Here, we surveyed translational and transcriptional changes after individual knockdown of 75 RPs, 44 from the large subunit (60S) and 31 from the small subunit (40S), by Ribo-seq and RNA-seq analyses. Deficiency of individual RPs altered specific subsets of genes transcriptionally and translationally. RP genes were under cotranslational regulation upon ribosomal stress, and deficiency of the 60S RPs and the 40S RPs had opposite effects. RP deficiency altered the expression of genes related to eight major functional classes, including the cell cycle, cellular metabolism, signal transduction and development. 60S RP deficiency led to greater inhibitory effects on cell growth than did 40S RP deficiency, through P53 signaling. Particularly, we showed that eS8/RPS8 deficiency stimulated apoptosis while eL13/RPL13 or eL18/RPL18 deficiency promoted senescence. We also validated the phenotypic impacts of uL5/RPL11 and eL15/RPL15 deficiency on retina development and angiogenesis, respectively. Overall, our study provides a valuable resource for and novel insights into ribosome regulation in cellular activities, development and diseases.


Acceptability of human papillomavirus vaccine for males: a review of the literature.
The quadrivalent human papillomavirus virus vaccine was recently licensed for use in males in the United States. This study reviews available published literature on acceptability among parents, health care providers, and young males. Among 23 published articles, half were conducted in the United States. The majority (87%) used quantitative survey methodology, and 13% used more explorative qualitative techniques. Convenience samples were used in most cases (74%) and 26% relied on nationally representative samples. Acceptability of a human papillomavirus virus (HPV) vaccine that protects against cervical cancer and genital warts was high in studies conducted among male college students (74%-78%) but lower in a community sample of males (33%). Among mothers of sons, support of HPV vaccination varied widely from 12% to 100%, depending on the mother's ethnicity and type of vaccine, but was generally high for a vaccine that would protect against both genital warts and cervical cancer. Health providers' intention to recommend HPV vaccine to male patients varied by patient age but was high (82%-92%) for older adolescent patients. A preference to vaccinate females over males was reported in a majority of studies among parents and health care providers. Messages about cervical cancer prevention for female partners did not resonate among adult males or parents. Future acceptability studies might incorporate more recent data on HPV-related disease, HPV vaccines, and cost-effectiveness data to provide more current information on vaccine acceptability.


Role of simple V-Y advancement flap in the treatment of complicated pilonidal sinus.
To evaluate our short term results of simple V-Y advancement flap for complicated pilonidal sinus. Prospective study. Yüzüncü Yýl University hospital, Van, Turkey. 23 patients aged 19-47 (mean 31) years with complicated pilonidal sinus treated between October 1994 and December 1996, of whom 9 had had previous operations for pilonidal sinus. Bilateral V-Y-plasty to close the defect after wide excision (n = 7), and unilateral V-Y-plasty (n = 16) were performed under spinal anaesthesia. There were no complications during the operation. There were 4 minor complications (17%) consisted of seroma (n = 2) and severe wound pain, and wound infection (n = 1 each). All patients were discharged within 10 days of operation and returned to work within 3 weeks. The mean follow up was 18 months (range 10-25) and no recurrences have occurred so far. Simple V-Y advancement flap may prove to be useful in patients with recurrent and complicated pilonidal sinuses.


Pediatric telerehabilitation medicine: Making your virtual visits efficient, effective and fun.
The COVID-19 pandemic has accelerated many changes in medicine including the transition from providing care in person to providing care via technology enabled telemedicine. The benefits of telemedicine visits with a Pediatric Rehabilitation Medicine (PRM) provider, also known as telerehabilitation medicine visits, are numerous. Telerehabilitation medicine provides an opportunity to deliver timely, patient and family-centric rehabilitation care while maintaining physical distance and reducing potential COVID-19 exposure for our patients, their caregivers and medical providers. Telerehabilitation medicine also allows for access to PRM care in rural areas or areas without medical specialty, virtual in-home equipment evaluation, and reduced travel burden. Because of these and many other benefits, telerehabilitation medicine will likely become part of our ongoing model of care if barriers to telemedicine continue to be lowered or removed. This paper is intended to establish a foundation for pediatric telerehabilitation medicine visit efficiency and effectiveness in our current environment and into the future.


Involvement of family members in life with type 2 diabetes: Six interconnected problem domains of significance for family health identity and healthcare authenticity.
Family involvement plays a key role in diabetes management. Problems and challenges related to type 2-diabetes often affect the whole family, and relatives are at increased risk of developing diabetes themselves. We highlight these issues in our objectives: (1) to uncover specific family problems associated with mutual involvement in life with type 2-diabetes and (2) to analytically look at ways of approaching these problems in healthcare settings. Qualitative data were gathered in participatory problem assessment workshops. The data were analysed in three rounds using radical hermeneutics. Problems were categorized in six domains: knowledge, communication, support, everyday life, roles and worries. The final cross-analysis focusing on the link between family identity and healthcare authenticity provided information on how the six domains can be approached in healthcare settings. The study generated important knowledge about problems associated with family involvement in life with type 2 diabetes and about how family involvement can be supported in healthcare practice.


[Effect of pharmacological substances on nociceptive vasomotor reflexes in experiments on unanesthetized animals].
Experiments on unanesthetized cats (conscious and curarized) were made to analyze the method of studying the effect of pharmacological substances on the pressor vasomotor reflexes produced by nociceptive stimulation. It was shown that the activity profiles of the drugs depend not only on their cardiovascular properties but also on the parameters of stimulation applied to the reflex recording, which is related to the shape of the curve of reflex magnitude dependence on the stimulation intensity. The most precise test in the application of the method to the unanesthetized animals involved the recording of the threshold of reflex occurrence, with the use of curare-like drugs being mandatory. Making of experiments without use of the curare-like agents or without considering the shape of the curve of reflex magnitude dependence on the parameters of stimulation might lead to errors in the appraisal of the results obtained.


Clinical usefulness of contrast-enhanced MP-RAGE of the brain.
Our purpose was to evaluate the usefulness of a 3D T1-weighted gradient-echo sequence (MP-RAGE) in clinical practice. We prospectively examined 200 patients with a variety of neurological disorders and symptoms. We compared lesion conspicuity and contrast enhancement on MP-RAGE images with conventional gadolinium-enhanced spin-echo (SE) T1-weighted images. Both the original MP-RAGE data and the reformatted images were characterised by improved differentiation between grey and white matter. More lesions were found on the 3D series, in both patients with neoplastic and non-neoplastic disease. Contrast enhancement of small oedematous lesions affecting the white matter in demyelinating disease was less obvious. Multiplanar reformatting, which can be realised in any desired plane and surface rendering with sophisticated segmentation algorithms superbly displayed the underlying anatomical relationships between lesions and normal brain structures. Excellent spatial resolution, the absence of posterior fossa artefacts and equivalent contrast enhancement resulted in an increased number of space-occupying lesions being found on the MP-RAGE images. Thus contrast-enhanced MP-RAGE is an alternative to conventional SE imaging in the investigation of intracranial masses. Although the total number of lesions found in patients with demyelinating disease was significantly higher on MP-RAGE, demonstration of blood-brain-barrier breakdown in active lesions was less obvious.


Post-Traumatic Growth of Nurses Who Faced the COVID-19 Epidemic and Its Correlation With Professional Self-Identity and Social Support.
To investigate post-traumatic growth (PTG) and analyze its correlation with professional self-identity and social support in Chinese nurses who faced the coronavirus disease 2019 (COVID-19) epidemic. A cross-sectional descriptive design was used in this study. An online questionnaire was completed by 266 nurses who faced the COVID-19 emergency in Hubei Province, China. The Post-traumatic Growth Inventory (PTGI), Professional Self-identity Scale, and Perceived Social Support Scale were used to assess the level of PTG, professional self-identity, and social support. Descriptive, univariate analysis and multiple regression analyses were used in exploring related influencing factors. Participants' mean scores were 96.26 (SD = 21.57) for PTG, 115.30 (SD = 20.82) for professional self-identification, and 66.27 (SD = 12.90) for social support. Multiple regression analysis showed that nurses from other provinces moving to support Hubei Province, professional self-identity, and social support were the main factors affecting nurse stress (p = 0.014, < 0.001, and 0.017, respectively). Professional self-identity and social support were positively correlated with PTG (r = 0.720 and 0.620, respectively). There was a phenomenon of PTG when the nurses faced COVID-19 in Hubei Province. Providing an active coping style helps to improve the level of PTG.


Prevalence of active Chlamydia trachomatis infection at the time of exploratory laparotomy for ectopic pregnancy.
Cultures of the fallopian tube, cul-de-sac, and cervix were obtained from 50 patients undergoing exploratory laparotomy for ectopic pregnancy. Chlamydia trachomatis was cultured from the cervix in four patients (8%). All the cultures from the fallopian tube or cul-de-sac were negative. Immunofluorescent stain of deparaffinized cross-sections of fallopian tube at the site of tubal involvement with the ectopic pregnancy failed to reveal any C trachomatis inclusions.


Modulated excitation infrared spectrophotometer.
The design and construction of a modulated excitation infrared spectrophotometer that allows detection of photoinduced transients in the spectral range 3000-4000 em(-1) is described. The lifetime range of photoproduced species is 10(-1)-10(-5) sec. Information about kinetics may be obtained by amplitude and phase measurements. The sensitivity achievable by single and double modulation is discussed in detail. Performance of the instrument is illustrated by detection of four transient photoproducts of pyrocatechol, distinguishable by phase measurements. Estimated lifetimes are within 1 msec and 40 msec.


Does COVID-19 infection change the need for future surgical interventions? An exploratory analysis.
Background: It is unknown whether recovery from coronavirus disease 2019 (COVID-19) infection leads to an increased need for common surgical procedures. Our objective was to conduct an exploratory analysis of surgical procedures performed after a documented COVID-19 infection. Methods: We conducted a retrospective cohort study using routinely collected data from the province of Ontario, Canada. We identified individuals with a positive COVID-19 test between February 1 2020 and May 31 2020, and matched them 1:2 with individuals who had a negative COVID-19 test during the same period. We used physician billing codes to identify the ten most frequent surgical procedures in the COVID-19 cohort. An at-risk period 30 days after the first positive COVID-19 swab (or matched index date in the control group) until November 30 2020 was used. Cox proportional hazard models (adjusted for important baseline differences) are reported with hazard ratios (HR) and 95% confidence intervals. Results: After exclusions and matching, we had 19,143 people in the COVID-19 cohort, and 38,286 people in the control cohort. The top ten surgical procedures were hand/wrist fracture fixation, cesarean-section, ureteral stent placement, cholecystectomy, treatment of an upper tract urinary stone, hysterectomy, femur fracture repair, hip replacement, transurethral prostatectomy, and appendectomy. There was a significantly reduced hazard of requiring upper tract renal stone surgery (adjusted hazard ratio [aHR] 0.50, 95% confidence interval [CI] 0.29-0.87) or ureteral stent placement (aHR 0.54, 95%CI 0.36-0.82), or undergoing a cholecystectomy (aHR 0.43, 95%CI 0.26-0.71) among those with a prior positive COVID-19 test. Conclusions: After a COVID-19 infection there is not an increased risk of needing several common surgical procedures. There appears to be a reduced risk of renal stone disease treatment and ureteral stent placement, and a reduced risk of cholecystectomy, however understanding the reasons for this will require further study.


The SnRK1A protein kinase plays a key role in sugar signaling during germination and seedling growth of rice.
Sugars repress alpha-amylase expression in germinating embryos and cell cultures of rice (Oryza sativa) through a sugar response complex (SRC) in alpha-amylase gene promoters and its interacting transcription factor MYBS1. The Snf1 protein kinase is required for the derepression of glucose-repressible genes in yeast. In this study, we explored the role of the yeast Snf1 ortholog in rice, SnRK1, in sugar signaling and plant growth. Rice embryo transient expression assays indicated that SnRK1A and SnRK1B act upstream and relieve glucose repression of MYBS1 and alphaAmy3 SRC promoters. Both SnRK1s contain N-terminal kinase domains serving as activators and C-terminal regulatory domains as dominant negative regulators of SRC. The accumulation and activity of SnRK1A was regulated by sugars posttranscriptionally, and SnRK1A relieved glucose repression specifically through the TA box in SRC. A transgenic RNA interference approach indicated that SnRK1A is also necessary for the activation of MYBS1 and alphaAmy3 expression under glucose starvation. Two mutants of SnRK1s, snrk1a and snrk1b, were obtained, and the functions of both SnRK1s were further studied. Our studies demonstrated that SnRK1A is an important intermediate in the sugar signaling cascade, functioning upstream from the interaction between MYBS1 and alphaAmy3 SRC and playing a key role in regulating seed germination and seedling growth in rice.


An endogenous mCherry-tagged COSA-1 as a crossover investigation tool in Caenorhabditis elegans.
The C. elegans cosa-1 gene encodes the crossover site-associated-1 (COSA-1) protein, a cyclin-related protein that functions in promoting crossovers (COs) during meiosis. Previous studies regarding CO dynamics in live C. elegans have mostly relied on the green fluorescent protein-tagged cosa-1 transgenic strain, which was generated by the microparticle bombardment method. Here, we insert the red fluorescence protein mCherry at the C-terminal of the cosa-1 gene to establish cosa-1::mCherry transgenic worm by the CRISPR/Cas9 technique. The COSA-1::mCherry was observed to appear from the early pachytene, and disappear in the diplotene zone of the germline, with 6 COSA-1:: mCherry foci in the late pachytene, which colocalized with GFP::COSA-1 from AV630 strain. Furthermore, the transgenic strain harboring a cosa-1::mCherry fusion shows no defect in the brood size, progeny viability and male frequency, which provides a useful tool for the meiotic analysis in C. elegans .


[Possibilities of cavinton therapy regimen for infusions and cavinton comforte in acute and early recovery periods after ischemic stroke].
To study the efficacy of a current regimen of treatment with cavinton for infusions and cavinton comforte in patients with ischemic stroke in acute and early recovery periods and to evaluate an impact of treatment on erythrocyte deformity using atomic power microscopy. One hundred and sixty-four patients with hemispheric ischemic stroke, aged from 30 to 79 years, were randomized into main (n=100) and control (n=64) groups. Patients of the main group received complex treatment (basic therapy and cavinton R for drop infusions (10 intravenously during 10 days) followed by cavinton R comforte in dose 10 mg, 1 tablet 3 times a day during 90 days). Patients of the control group received basic therapy only. NIHSS, the Rankin scale, the Barthel index, MMSE, MоCA, the Rivermead scale, Beck depression scale, HADS were used to measure the severity of patient's state. To study the erythrocyte membrane by estimating Young's modulus, dry preparations were made with the following scanning of erythrocytes using atomic power microscopy. Positive changes on all scales were observed in both groups. Higher scores on NIHSS, Rankin, Barthel, MоCA, MMSE, Rivermead mobility index were found in the main group compared to the controls. There were no differences in scores on the Beck depression scale and HADS. A decrease in Young's modulus was found in the main group while in the control group this index remained unchanged. More rapid and complete regression of neurological deficit, better recovery of self-care function, cognitive function and social activity, an increase in erythrocyte membrane elasticity were found in the main group compared to the control one. These results indicate the efficacy of cavinton R and cavinton R comforte in the regimen used in complex treatment in acute and early recovery periods after ischemic stroke.


A Fuzzy Rule-Based Penalty Function Approach for Constrained Evolutionary Optimization.
This paper proposes a novel fuzzy rule-based penalty function approach for solving single-objective nonlinearly constrained optimization problems. Of all the existing state-of-the-art constraint handling techniques, the conventional method of penalty can be easily implemented because of its simplicity but suffers from the lack of robustness. To mitigate the problem of parameter dependency, several forms of adaptive penalties have been suggested in literature. Instead of identifying a complex mathematical function to compute the penalty for constraint violation, we propose a Mamdani type IF-THEN rule-based fuzzy inference system that incorporates all the required criteria of self-adaptive penalty without formulating an explicit mapping. Effectiveness of the proposed constrained optimization algorithm has been empirically validated on the basis of the standard optimality theorems from the literature on mathematical programming. Simulation results show that fuzzy penalty not only surpasses its existing counterpart i.e., self adaptive penalty, but also remain competitive against several other standard as well as currently developed complex constraint handling strategies.


Inverted terminal repeats permit the average length of amplified DNA fragments to be regulated during preparation of cDNA libraries by polymerase chain reaction.
A simple polymerase chain reaction (PCR)-based technique for construction of cDNA libraries starting with very small amounts of cells or tissues is described. The technique is based on the insertion of inverted terminal repeats into amplified cDNAs which permit short molecules to generate "pan"-type structures at each cycle of PCR amplification and thus to escape annealing with primers. This allows one to avoid amplification of primer dimers and makes it possible to perform oligonucleotide tailing of the first cDNA strands followed by PCR amplification in the same tube. Moreover, the average size of amplified cDNAs can be controlled by varying the primer concentration.


The smoking paradox: exploring why attitudes toward cigarette smoking are a weak predictor of cigarette smoking.
An attitude change perspective represents a central line of research in the smoking literature. This line of research focuses on influencing individuals' attitudes toward smoking in order to alleviate the negative outcomes of smoking and to achieve positive smoking behaviours. This line of research, however, does not explain why attitudes toward cigarette smoking are a weak predictor of cigarette smoking, an indication of a smoking paradox. The current study introduces two domain-general factors to explore this smoking paradox. We used an online survey and collected data from American subjects (n = 328) via a crowdsourcing platform, Amazon Mechanical Turk, in 2018. We found that the association between attitude toward smoking and the likelihood of smoking is significantly weaker when individuals perceive a low probability of risk and/or believe that this probable risk will only occur in the distant future, after many years. These results suggest that smoking may not be consistent with attitude because individuals perceive low probability of risk and/or they temporally discount the occurrence of this probable risk. The results suggest that novel strategies that incorporate the concepts of perceived risk probability and temporal discounting of the probable risk are needed for smoking cessation.


Communication Patterns Among Male Couples with Open and Monogamous Agreements.
Male couples in open relationships tend to have as equally fulfilling relationships as monogamous male couples; however, less is known about communication differences between monogamous and open couples. Because couples with open agreements permit sex with outside partners, they must navigate different relationship issues than monogamous couples, and this can translate to differences in communication. We therefore examined differences between cisgender men in monogamous versus open relationships regarding communication about sexual agreements, safety agreements, breaking of sexual and safety agreements, the disclosure of broken sexual and safety agreements, and general relationship communication. Using a sample of 395 couples, we found that while certain aspects of communication are different for monogamous couples compared to open couples, similarities also exist. Specifically, we identified no differences in how explicitly couples discussed their sexual and safety agreements, attitudes toward communication about safety agreements, and mutual avoidance and withholding communication. However, monogamous couples had more positive attitudes toward communication about sexual agreements. The results were mixed on the perceived impact that broken safety agreements had on communication with the primary partner. Our results are interpreted with attention to relationship well-being and implications for safer sex practices.


Favipiravir Inhibits Mayaro Virus Infection in Mice.
Mayaro virus (MAYV) is an emergent alphavirus that causes MAYV fever. It is often associated with debilitating symptoms, particularly arthralgia and myalgia. MAYV infection is becoming a considerable health issue that, unfortunately, lacks a specific antiviral treatment. Favipiravir, a broad-spectrum antiviral drug, has recently been shown to exert anti-MAYV activity in vitro. In the present study, the potential of Favipiravir to inhibit MAYV replication in an in vivo model was evaluated. Immunocompetent mice were orally administrated 300 mg/kg/dose of Favipiravir at pre-, concurrent-, or post-MAYV infection. The results showed a significant reduction in infectious viral particles and viral RNA transcripts in the tissues and blood of the pre- and concurrently treated infected mice. A significant reduction in the presence of both viral RNA transcript and infectious viral particles in the tissue and blood of pre- and concurrently treated infected mice was observed. By contrast, Favipiravir treatment post-MAYV infection did not result in a reduction in viral replication. Interestingly, Favipiravir strongly decreased the blood levels of the liver disease markers aspartate- and alanine aminotransferase in the pre- and concurrently treated MAYV-infected mice. Taken together, these results suggest that Favipiravir is a potent antiviral drug when administered in a timely manner.


MRI pattern of progressive multifocal leukoencephalopathy (PML) in AIDS. Pathological correlations.
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease which occurs in immunodepressed subjects and is particularly frequent in AIDS. Some authors having drawn attention to the protean aspect of the disease and claimed that AIDS may lose its basic characteristics and affect the grey matter as well as the white matter, we reviewed a series of 8 patients who had been biopsied and/or autopsied and had been examined at least once by MRI. In this series, contrary to what is regularly observed in toxoplasmic abscesses we did not find any lesion of the grey matter or any mass effect. On the other hand, we confirmed that PLM is not multifocal in all cases and that it course may be interrupted by prolonged remissions. The MRI criteria for PML therefore are reliable, provided multiple T2-weighted slices in coronal plane are performed, clearly showing the anatomy of the white fibres affected. However, it must be borne in mind that HIV-infected patients often have other associated brain pathologies, especially when the immune deficiency increases.


An immunochromatographic test strip for on-site detection of Ralstonia solanacearum in tobacco leaves and soil.
Tobacco bacterial wilt is one of the most devastating soil-borne diseases in tobacco-producing regions worldwide. It is often responsible for significant economic losses during tobacco production. A rapid, specific, and high-throughput on-site detection method is important for plant disease management. In this study, monoclonal antibody 3H3 and polyclonal antibody 0344 specific for Ralstonia solanacearum were used to prepare a colloidal gold-based immunochromatographic test strip (ITS). Under optimal conditions, the detection limit of the ITS was 105 CFU/mL. The ITS was able to detect different R. solanacearum strains collected from Shandong, Yunnan, Guizhou, and Sichuan provinces in China. Moreover, the ITS was highly specific for R. solanacearum, with no cross-reactivity with Alternaria alternata (Fries) Keissler, Pseudomonas syringae pv. angulata, and P. syringae pv. tabaci. Furthermore, R. solanacearum-spiked tobacco leaves and soil were used to evaluate the matrix interference of the developed ITS, which indicated the test strip was unaffected by leaf size or soil abundance.


Genomic and Non-genomic Action of Neurosteroids in the Peripheral Nervous System.
Since the former evidence of biologic actions of neurosteroids in the central nervous system, also the peripheral nervous system (PNS) was reported as a structure affected by these substances. Indeed, neurosteroids are synthesized and active in the PNS, exerting many important actions on the different cell types of this system. PNS is a target for neurosteroids, in their native form or as metabolites. In particular, old and recent evidence indicates that the progesterone metabolite allopregnanolone possesses important functions in the PNS, thus contributing to its physiologic processes. In this review, we will survey the more recent findings on the genomic and non-genomic actions of neurosteroids in nerves, ganglia, and cells forming the PNS, focusing on the mechanisms regulating the peripheral neuron-glial crosstalk. Then, we will refer to the physiopathological significance of the neurosteroid signaling disturbances in the PNS, in to identify new molecular targets for promising pharmacotherapeutic approaches.


Crystallization and preliminary X-ray characterization of the Bacillus amyloliquefaciens YwrO enzyme.
CB1954 is an anticancer prodrug that is currently in clinical trials coupled with the Escherichia coli flavoenzyme nitroreductase (NTR) for use in directed-enzyme prodrug therapy (DEPT). The NTR enzyme is responsible for the conversion of the prodrug into a cytotoxic agent. The bifunctional alkylating agent produced by this bioactivation process leads to DNA damage and death of cancer cells. Recently, a novel flavoenzyme from Bacillus amyloliquefaciens, YwrO (Bam YwrO), was reported to be able to reduce CB1954 from its noncytotoxic form into its active form. The crystallization and preliminary X-ray diffraction analysis of two crystal forms of Bam YwrO are reported. The first crystal form is orthorhombic, with space group P22(1)2(1), and diffracts X-rays to 2.18 A resolution. The second crystal form is tetragonal, with space group P4(1), and diffracts X-rays to 3.4 A. Determination of the Bam YwrO crystal structure will provide an understanding of the molecular recognition between this enzyme and the anticancer prodrug CB1954.


[Development and Application for Drug-safety and Efficacy Using a Large Claims Data].
Recent years, evidences for medical safety and efficacy are accelerated-developing using medical big data. Medical big data were adequate for analyzing 1) rare events that difficult for finding in each hospital, 2) for comparison of bench marks obtained routine work between average data in large number of hospitals and specific hospital data and 3) prescription surveys etc. As so far, these analyses using medical big data were conducted by academia and/or researcher. However, in these days, evidences using medical big data were focused on hospital pharmacists little by little. In this review, we show 3 researches using large claims data such as 1) risk factors assessing for failed low-density lipoprotein level achievement in members of the working-age population, 2) prevalence of drug-drug interaction in atrial fibrillation patients and 3) assessment of "look-alike" packaging designs related to medication errors using information technology and large claims data. Medical big data such as large claims data analysis is useful and suitable for building evidences according to medical staffs-needs.


Loss of phosphatase activity in myotubularin-related protein 2 is associated with Charcot-Marie-Tooth disease type 4B1.
Mutations in the gene encoding myotubularin-related protein 2 (MTMR2) are responsible for autosomal recessive Charcot-Marie-Tooth disease type 4B1 (CMT4B1), a severe hereditary motor and sensory neuropathy characterized by focally folded myelin sheaths and demyelination. MTMR2 belongs to the myotubularin family, which is characterized by the presence of a phosphatase domain. Myotubularin (MTM), the archetype member of this family, is mutated in X-linked myotubular myopathy. Although MTMR2 and MTM are closely related, they are likely to have different functions. Recent studies revealed that MTM dephosphorylates specifically phosphatidylinositol 3-phosphate. Here we analyze the biochemical properties of the mouse Mtmr2 protein, which shares 97% amino acid identity with human MTMR2. We show that phosphatidylinositol-3-phosphate is also a substrate for Mtmr2, but, unlike myotubularin, Mtmr2 dephosphorylates phosphatidylinositol 3,5-bisphosphate with high efficiency and peak activity at neutral pH. We demonstrate that the known disease-associated MTMR2 mutations lead to dramatically reduced phosphatase activity, suggesting that the MTMR2 phosphatase activity is crucial for the proper function of peripheral nerves in CMT4B1. Expression analysis of Mtmr2 suggests particularly high levels in neurons. Thus, the demyelinating neuropathy CMT4B1 might be triggered by the malfunction of neural membrane recycling, membrane trafficking, and/or endocytic or exocytotic processes, combined with altered axon-Schwann cell interactions. Furthermore, the different biochemical properties of MTM and MTMR2 offer a potential explanation for the different human diseases caused by mutations in their respective genes.


The effects of early- or mid-gestation nutrient restriction on bovine fetal pancreatic development.
Research on the effects of nutrient restriction in beef cows on fetal pancreatic development is limited. To address this, multiparous Angus-cross cows (n = 22) were fed either control (CON; to gain 1 kg/wk) or nutrient-restricted (NR; 0.55% NEm) diets based on NRC requirements. On d 30 of gestation, cows were blocked by body condition and randomly assigned to one of three nutritional regimes: CON fed from d 30 to 190 (n = 8), or NR/C (n = 7) or C/NR (n = 7) fed either the CON or NR diet from d 30 to 110 followed by CON or NR from d 110 to 190 of gestation. Cows were harvested on d 190 of gestation, and blood samples, fetal weights, and fetal tissue weights and samples were collected. Pancreas samples were embedded in paraffin and sectioned for standard immunohistochemistry procedures to quantify insulin-positive β cells and number of apoptotic β cells using TUNEL staining. Data were analyzed via ANOVA using the general linear model procedure of SAS. At harvest, empty carcass weights were decreased (P = 0.036) in fetuses of C/NR and NR/C fed dams compared to fetuses of CON fed dams. Pancreas weight was decreased (P = 0.028) in fetuses of C/NR fed dams compared to CON fetuses; however, fetuses of NR/C fed dams were not different (P > 0.05) from fetuses of CON fed dams. Maternal and fetal serum insulin concentrations were not different (P > 0.05) in NR/C fed compared to CON fed; however, concentrations of insulin were decreased (P = 0.036 and P = 0.40, respectively) in C/NR fed compared to CON fed. Beta cell number was decreased (P = 0.009) in fetuses of NR/C and C/NR fed dams compared to fetuses of CON fed dams. Percentage of apoptotic cells was increased (P < 0.0001) in fetuses of NR/C and C/NR fetuses than fetuses of CON fed dams. This evidence suggests that nutrient restriction either during early- or mid-gestation can negatively impact fetal pancreatic development. However, mid-gestational nutritional insult is potentially recovered by reacclimation to a diet that meets requirements of the dam, thus reducing negative outcomes in fetal offspring.


Therapeutic Benefit of Galectin-1: Beyond Membrane Repair, a Multifaceted Approach to LGMD2B.
Two of the main pathologies characterizing dysferlinopathies are disrupted muscle membrane repair and chronic inflammation, which lead to symptoms of muscle weakness and wasting. Here, we used recombinant human Galectin-1 (rHsGal-1) as a therapeutic for LGMD2B mouse and human models. Various redox and multimerization states of Gal-1 show that rHsGal-1 is the most effective form in both increasing muscle repair and decreasing inflammation, due to its monomer-dimer equilibrium. Dose-response testing shows an effective 25-fold safety profile between 0.54 and 13.5 mg/kg rHsGal-1 in Bla/J mice. Mice treated weekly with rHsGal-1 showed downregulation of canonical NF-κB inflammation markers, decreased muscle fat deposition, upregulated anti-inflammatory cytokines, increased membrane repair, and increased functional movement compared to non-treated mice. Gal-1 treatment also resulted in a positive self-upregulation loop of increased endogenous Gal-1 expression independent of NF-κB activation. A similar reduction in disease pathologies in patient-derived human cells demonstrates the therapeutic potential of Gal-1 in LGMD2B patients.


Regeneration of dopaminergic neurons after 6-hydroxydopamine-induced lesion in planarian brain.
Planarians have robust regenerative ability dependent on X-ray-sensitive pluripotent stem cells, called neoblasts. Here, we report that planarians can regenerate dopaminergic neurons after selective degeneration of these neurons caused by treatment with a dopaminergic neurotoxin (6-hydroxydopamine; 6-OHDA). This suggests that planarians have a system to sense the degeneration of dopaminergic neurons and to recruit stem cells to produce dopaminergic neurons to recover brain morphology and function. We confirmed that X-ray-irradiated planarians do not regenerate brain dopaminergic neurons after 6-OHDA-induced lesioning, suggesting that newly generated dopaminergic neurons are indeed derived from pluripotent stem cells. However, we found that the majority of regenerated dopaminergic neurons were 5-bromo-2'-deoxyuridine-negative cells. Therefore, we carefully analyzed when proliferating stem cells became committed to become dopaminergic neurons during regeneration by a combination of 5-bromo-2'-deoxyuridine pulse-chase experiments, immunostaining/in situ hybridization, and 5-fluorouracil treatment. The results strongly suggested that G(2) -phase stem cells become committed to dopaminergic neurons in the mesenchymal space around the brain, after migration from the trunk region following S-phase. These new findings obtained from planarian regeneration provide hints about how to conduct cell-transplantation therapy for future regenerative medicine.


DOTS centre at a tertiary care teaching hospital: lessons learned and future directions.
In 1993, Government of India started the Revised National Tuberculosis Control Programme (RNTCP). A model Directly Observed Therapy, Short-Course (DOTS) centre was established at the All India Institute of Medical Sciences (AIIMS) to (i) identify the challenges and opportunities in establishing DOTS centres at tertiary care facilities, (ii) to teach the strategies of RNTCP to medical and paramedical staff, and (iii) to undertake relevant operational research connected with tuberculosis (TB) treatment and control. In this communication, we describe the experience of establishing a DOTS centre at India's premier medical institute and discuss the lessons learned. Since September 2001 through November 2002 AIIMS employees and their dependants diagnosed with tuberculosis were enrolled for treatment at AIIMS DOTS centre. One hundred sixty-eight patients were diagnosed as suffering from tuberculosis. Of these 49 patients were referred out and remaining 119 patients were treated at AIIMS DOTS centre. Treatment success was achieved in 80% (20/25) of new smear positive cases and the DOTS centre achieved other targets set up by the RNTCP. As the results of the pilot study at AIIMS DOTS centre were favourable, the facilities of AIIMS DOTS centre were extended to the general public from September 2002 onwards. Despite tremendous patient load at tertiary care facilities, it is possible to achieve targets established by the RNTCP. However, additional research needs to be conducted especially relating to drug resistance and surrogate markers of failure under RNTCP.


Reference-point-independent dynamics of molecular liquids and glasses in the tensorial formalism.
We apply the tensorial formalism to the dynamics of molecular liquids and glasses. This formalism separates the degrees of freedom into translational and orientational ones. Using the Mori-Zwanzig projection formalism, the equations of motion for the tensorial density correlators S(lmn,l'm'n')(q-->,t) are derived. For this we show how to choose the slow variables such that the resulting Mori-Zwanzig equations are covariant under a change of the reference point of the body fixed frame. We also prove that the memory kernels obtained from mode-coupling theory (MCT) including all approximations preserve the covariance. This covariance makes, e.g., the glass transition point, the two universal scaling laws and particularly the corresponding exponents independent on the reference point and on the mass and moments of inertia, i.e., they only depend on the properties of the potential energy landscape. Finally, we show that the corresponding MCT questions for linear molecules can be obtained from those for arbitrary molecules and that they differ from earlier equations that are not covariant.


Development of an expressed sequence tag (EST) resource for wheat (Triticum aestivum L.): EST generation, unigene analysis, probe selection and bioinformatics for a 16,000-locus bin-delineated map.
This report describes the rationale, approaches, organization, and resource development leading to a large-scale deletion bin map of the hexaploid (2n = 6x = 42) wheat genome (Triticum aestivum L.). Accompanying reports in this issue detail results from chromosome bin-mapping of expressed sequence tags (ESTs) representing genes onto the seven homoeologous chromosome groups and a global analysis of the entire mapped wheat EST data set. Among the resources developed were the first extensive public wheat EST collection (113,220 ESTs). Described are protocols for sequencing, sequence processing, EST nomenclature, and the assembly of ESTs into contigs. These contigs plus singletons (unassembled ESTs) were used for selection of distinct sequence motif unigenes. Selected ESTs were rearrayed, validated by 5' and 3' sequencing, and amplified for probing a series of wheat aneuploid and deletion stocks. Images and data for all Southern hybridizations were deposited in databases and were used by the coordinators for each of the seven homoeologous chromosome groups to validate the mapping results. Results from this project have established the foundation for future developments in wheat genomics.


Radicular pain caused by synovial cyst: an underdiagnosed entity in the elderly?
Synovial cyst is a recognized but infrequent cause of nerve root or spinal canal compression. The authors undertook a review of 839 decompressive spinal procedures performed over a 5-year period. They found seven cases in which the symptoms were caused by synovial cysts. Six of these cases were in a subgroup of 80 patients who were older than 60 years of age, which represents 7.5% of the total for this age group. More than 200 cases of this abnormality have been reported in the world literature, but the incidence, prevalence, and natural history remain unknown. The authors propose that the incidence of synovial cysts may be more common than recognized in the elderly and suggest that preoperative diagnosis may help limit the extent of the surgical approach.


In vitro activation of a galactosyl transferase involved in the osmotic regulation of ochromonas.
Osmotic regulation in the flagellate Ochromonas malhamensis Pringsheim is mainly mediated by fluctuations in the pool size of alpha-galactosyl-(1-->1)-glycerol (isofloridoside). A regulated key enzyme of isofloridoside metabolism is the galactosyl transferase producing isofloridoside phosphate. The activity of this enzyme in crude extracts can be increased 5- to 20-fold by incubation at pH 6. The activation occurs in a reaction with a Q(10) of 1.5 to 3 and is dependent on time and pH value. Inactivation of the activated form of the enzyme is also time-dependent, and is minimal at the pH value at which activation is optimal. The data suggest a regulation of the enzyme by chemical modification due to the action of auxiliary enzymes.


Discovery and Characterization of a Water-Soluble Prodrug of a Dual Inhibitor of Bacterial DNA Gyrase and Topoisomerase IV.
Benzimidazole 1 is the lead compound resulting from an antibacterial program targeting dual inhibitors of bacterial DNA gyrase and topoisomerase IV. With the goal of improving key drug-like properties, namely, the solubility and the formulability of 1, an effort to identify prodrugs was undertaken. This has led to the discovery of a phosphate ester prodrug 2. This prodrug is rapidly cleaved to the parent drug molecule upon both oral and intravenous administration. The prodrug achieved equivalent exposure of 1 compared to dosing the parent in multiple species. The prodrug 2 has improved aqueous solubility, simplifying both intravenous and oral formulation.


Ribozyme-catalyzed excision of targeted sequences from within RNAs.
We demonstrate that a group I intron-derived ribozyme from the opportunistic pathogen Pneumocystis carinii can bind an RNA in trans and excise from within it an internal segment, resulting in the splicing of the remaining ends of the RNA back together (the trans excision-splicing reaction). The reaction is intramolecular with regard to substrate. The ribozyme targets its substrate by base pairing with two or three noncontiguous regions on the substrate, and the reaction occurs through a nucleotide cofactor independent mechanism. The excised segment can be as long as 28 nucleotides, or more, and as little as one nucleotide. The potential usefulness of this reaction is demonstrated by engineering a ribozyme that excises the triplet-repeat expansion region from a truncated myotonic dystrophy protein kinase transcript mimic in vitro.


Prevalence and recognition of obstructive sleep apnea in Chinese patients with type 2 diabetes mellitus.
Obstructive sleep apnea (OSA) is associated with disorders of glucose metabolism. Previous studies revealed a high prevalence of OSA among subjects with type 2 diabetes mellitus (DM). The aims of this study were to determine the prevalence of OSA and associated clinical factors in Chinese patients with DM. All records of the DM clinic at a teaching hospital in Hong Kong were screened between January 2007 and June 2008. Inclusion criteria for patients were Chinese, aged 18 to 75 years, with type 2 DM. Patients with unstable medical illnesses, gestational diabetes, or on renal replacement therapy were excluded. Of 3,489 records screened, 1,859 subjects were eligible. A random sample of 663 (mean age, 58.2 ± 10.8; mean BMI, 26.0 ± 4.6), except six with known OSA, were invited for polysomnography (PSG). Of 165 subjects on which PSG was performed, OSA was diagnosed (apnea-hypopnea index [AHI] ≥ 5.0/h) in 89 subjects (53.9%, median Epworth Sleepiness Scale, 6 [interquartile range 3, 10]). Fifty-four (32.7%) had moderate/severe OSA (AHI ≥ 15/h). The estimated OSA prevalence in this diabetic cohort was 17.5% (24.7% in men, 10.3% in women). Regression analysis identified that AHI was associated independently with higher BMI, advanced age, male sex, and higher diastolic BP (R(2) = 29.6%). The adjusted OR of requiring three or more antihypertensive drugs in moderate/severe OSA was 2.48 (95% CI, 1.05-5.87). No association between glycemic control (HbA1c) and sleep was identified. In conclusion, OSA is more prevalent in Chinese adults with DM than in the general population. A high index of suspicion for OSA in patients with DM is warranted, because they may not have overt daytime sleepiness.


Short-bowel syndrome: a review of the role of nutrition support.
Advances in long-term venous access devices and in parenteral nutrition solutions have made it possible for patients with severe short bowel syndrome to survive and to live in our society. The spectrum of this disease is such that some patients may be able to lessen their dependence or even become free from parenteral therapy. This review will discuss the role of nutrition support in the patient with short bowel syndrome.


The Prognostic Role of STEAP1 Expression Determined via Immunohistochemistry Staining in Predicting Prognosis of Primary Colorectal Cancer: A Survival Analysis.
STEAP1 (six transmembrane epithelial antigen of the prostate 1) is a transmembrane protein that functions as a potential channel or transporter protein. It is overexpressed in certain cancers and is viewed as a promising therapeutic target. However, the prognostic role of STEAP1 is still controversial, and no role for STEAP1 has yet been indicated in colorectal cancer. The aim of this study was to investigate the possible association of STEAP1 expression with colorectal cancer prognosis. STEAP1 expression was analyzed by immunohistochemical staining of a tissue array of 165 cancer specimens from primary colorectal cancer patients. The mean and medium follow-up times after surgery were 5.1 and 3.9 years, respectively. A total of 139 patients died during the 13 years of follow-up in the survey period. The prognostic value of STEAP1 with respect to overall survival was analyzed by Kaplan-Meier analysis and Cox proportional hazard models. In total, 164 samples displayed detectable STEAP1 expression in the cytoplasm and membrane. Low STEAP1 expression was correlated with poor overall survival (five-year survival: 33.7% vs. 57.0%, low expression vs. high expression, p = 0.020). Accordingly, multivariate analysis identified low STEAP1 expression as an independent risk factor (hazard ratio = 1.500, p = 0.018), especially in elderly patients or those with late stage cancers, late T values, and early N values. We suggest that analysis of STEAP1 expression by immunohistochemical staining could serve as an independent prognostic marker for colorectal patients. This finding should be validated by other investigative groups.


Intravascular fasciitis leading to an aortic dissection. A case report.
Here we report on the case of a 61-year-old female with an accidental finding of intravascular fasciitis (IVF) affecting the ascending aorta in a specimen resected due to an acute aortic dissection. No infiltrative process of the aorta or surrounding soft tissues was grossly apparent. Microscopically, the lesion had poorly defined margins and was composed of plump spindle- and oval-shaped cells set in an abundant myxoid stroma. Immunohistochemically, cytoplasmic positivity for β-catenin was observed and about 25% of cells were positive for calponin. The Ki-67 index was approximately 25% (increasing to about 50% in hot spot areas). Occasional isolated cells also showed positivity for alpha actin. Other markers were all negative in the tumor cells including; smooth muscle actin, desmin, h-caldesmon, D2-40, DOG1, S100 protein, CD34, CD31, ERG, melan A, HMB45, IgG, IgG4, ALK, cytokeratin AE1/AE3, and LCA. Intravascular fasciitis is a benign myofibroblastic proliferation which most commonly occurs in subcutaneous tissues and may mimic malignancy. To the best of our knowledge this is only the 2nd ever reported case of IVF affecting the aorta. Keywords: intravascular fasciitis - nodular fasciitis - soft tissue lesions - myofibroblasts - aorta.


Stimulation of Mitochondrial Calcium Uptake by Light during Growth of Corn Shoots.
Ca(2+) uptake in mitochondrial fractions, isolated on Percoll discontinuous density gradients, from light- and dark-grown corn (Zea mays L. var W64A x W182E) shoots was characterized by dual wavelength spectroscopy and the Ca(2+)-sensitive dye murexide. In light-grown seedlings, the rate of mitochondrial Ca(2+) uptake was about 40 nanomoles per minute per milligram of mitochondrial protein. A portion of the Ca(2+) uptake required an exogenous supply of ATP (65%) while the remaining 35% was the respiratory substrate-dependent reaction. Ruthenium red (2 micromolar) completely inhibited both ATP- and substrate-dependent reactions. There was no detectable Ca(2+) efflux from the mitochondria with the inhibitor. When the mitochondrial fraction was prepared from the dark-grown shoots, the rate of uptake, in particular the ATP-dependent reaction, was greatly reduced. The dark treatment caused a reduction in mitochondrial Ca content which is largely due to the reduction of Ca associated with the mitochondrial membrane rather than to a reduction of Ca in the soluble matrix.


Procedure-related risk of miscarriage following chorionic villus sampling and amniocentesis.
To estimate the procedure-related risks of miscarriage following chorionic villus sampling (CVS) and amniocentesis in a large unselected screened population, and to determine whether these risks are consistent with those reported in systematic reviews and meta-analyses. This was a retrospective cohort study carried out on data obtained from a large fetal medicine unit in the UK between January 2009 and May 2018. We included all women with singleton pregnancy who booked for pregnancy care at our unit before 20 weeks' gestation, after excluding those with multiple pregnancy, major fetal defect, pregnancy termination and loss to follow-up. We estimated the risk of miscarriage in women who underwent a CVS or amniocentesis as well as in those who did not have an invasive procedure. The procedure-related risk of miscarriage was estimated as risk difference (95% CI) between the two groups. Univariate and multivariate regression analyses were used to derive odds ratios (95% CI) and determine which maternal and pregnancy characteristics provided a significant contribution in the prediction of miscarriage and whether CVS or amniocentesis provided a significant independent contribution. During the study period, 45 120 singleton pregnancies were booked for pregnancy care at our hospital, of which 1546 had an invasive procedure. We excluded 1429 (3.2%) pregnancies due to fetal defects, termination of pregnancy or missing outcomes. Of the 43 691 pregnancies included in the study population, 861 underwent CVS and 375 amniocentesis. In pregnancies that underwent CVS, the risk of miscarriage was 1.5% (13/861), compared with 1.2% (476/39 152) in pregnancies that had first-trimester combined screening and did not have an invasive procedure (P = 0.437). In pregnancies that underwent an amniocentesis, the risk of miscarriage was 0.8% (3/375), compared with 1.2% (491/42 463) in those that did not undergo an invasive procedure (P = 0.520). Univariate and multivariate regression analysis demonstrated that there was no significant contribution in the prediction of the risk of miscarriage from CVS (P = 0.399 and P = 0.592, respectively) or amniocentesis (P = 0.543 and P = 0.550, respectively). The risk of procedure-related loss attributed to CVS was 0.29% (95% CI, -0.53 to 1.12%) and that following amniocentesis was -0.36% (95% CI, -1.26 to 0.55%), which was not significantly different from the risk in women who did not have any procedure. The procedure-related risks of miscarriage following CVS and amniocentesis in our study are considerably lower than those currently quoted and are consistent with the estimates of such risks reported by systematic reviews and meta-analyses. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.


Radioprotective effect of misoprostol on mouse spermatogonial stem cells.
The radioprotective effects of misoprostol, a synthetic stable analogue of prostaglandin E1, on spermatogonial stem cells of C3H/HeH x 101/F1 hybrid mice (3H1) were analysed by establishing dose--response relationships for stem cell killing by X-rays in mice that were pretreated with misoprostol. Spermatogonial stem cell killing was studied through determination of the percentage of tubular cross-sections showing repopulation at 10 days after irradiation. In control mice, the D0 values ranged between 1.7 and 3.6 Gy, dependent on the stage of the cycle of the seminiferous epithelium the cells were in. As found previously, proliferating spermatogonial stem cells were much more radioresistant than quiescent stem cells. In the misoprostol-pretreated animals the spermatogonial stem cells were more radioresistant, the D0 values ranging from 3.6 to 5.0 Gy. Both proliferating and quiescent spermatogonial stem cells were protected by misoprostol. As the dose--response curves in control and misoprostol-pretreated mice showed about the same extrapolation number to the y-axis it was concluded that the misoprostol pretreatment did not alter the kinetics of the repopulation process.


Patterns, Outcomes and Predictors of Pediatric Medical Admissions at Gadarif Hospital in Eastern Sudan.
The reduction of childhood mortality is a reliable indicator of a national health system's progress and improvement. Sudan's population is still suffering from communicable diseases, with a considerably higher mortality rate among children. Efforts are therefore needed to reduce mortality and achieve the Millennium Development Goals and Sustainable Development Goals. This study was conducted to determine the morbidity, mortality and outcomes of children admitted to Gadarif Hospital in eastern Sudan. A retrospective study was conducted by reviewing the medical files of pediatric patients who were admitted to Gadarif Hospital between March 1, 2019 and March 31, 2020. A total of 740 medical files were reviewed. Most, 453 (61.2%) of the admissions were males. The median (interquartile range) age was 3.0 (8.0) years and 433 (58.8%) of the admissions were under 5 years of age. The median (interquartile range) of the length of hospital stay was 9.0 (12.0) days. Visceral leishmaniasis, malnutrition, severe malaria, sickle cell disease, acute watery diarrhea, severe anemia (regardless of its cause), septicemia and acute respiratory infection were the most common causes of admission. The mortality rate was 5.7%, and it was significantly higher in females than males [24/287 (8.4%) vs. 18/453 (4.0%), P = 0.01] and in children under 5 years [36/433 (8.3%) vs. 6/307 (2.0%), P < 0.001]. Malnutrition, visceral leishmaniasis, septicemia and meningitis/encephalitis were the main diseases causing death in the study population. The case fatality rate was not significantly different in malnutrition than in visceral leishmaniasis [9/93 (9.7%) vs. 7/178 (3.9%), P = 0.05]. The main causes of morbidity and mortality for children admitted to Gadarif Pediatric Hospital were communicable diseases. The mortality rate was 5.7%. Females and children under 5 years were the most vulnerable groups for fatality.


The effects of surface and biomolecules on magnesium degradation and mesenchymal stem cell adhesion.
A novel class of biodegradable metals, magnesium (Mg) and Mg-based alloys, has recently attracted much attention because of unique biodegradation and mechanical properties for medical applications. Ideally, Mg-based devices should degrade no faster than the degradation products can be eliminated efficiently from the body. Additionally, for orthopedic and maxillofacial applications, the implant integration with the surrounding bone is critical for its clinical success. Therefore, it is necessary to thoroughly characterize Mg surface and degradation and investigate how these characteristics influence its interactions with essential cells, for example, bone marrow derived mesenchymal stem cells. The objectives of this study were to investigate (1) the effects of two surface conditions (the presence vs. absence of surface oxides) on Mg degradation and mesenchymal stem cell adhesion, and (2) the effects of two essential aqueous environments (the presence vs. absence of physiological ions and proteins) on Mg degradation. In an effort towards standardizing testing methods for Mg alloys, consistent and well-controlled experimental methods were designed to characterize the surface and degradation of Mg and its interactions with cells. The results demonstrated that original surface (oxidized vs. polished) conditions had a less pronounced effect on regulating initial cell adhesion, but did affect surface morphology and composition of the Mg samples after 24 h of cell culture. The presence versus absence of biological ions and proteins had a significant effect on Mg degradation mode and rate. In conclusion, the material surface and anatomical sites of implantation dependent on the intended applications must be carefully considered while assessing Mg alloys in vitro or in vivo for medical applications. Standardized testing procedures and methods are critically needed for developing more effective medical-grade Mg alloys.


Comments on: involving service users in the qualitative analysis of patient narratives to support healthcare quality improvement.
Some previous researchers (Locock et al) have written about what may be the best way for public contributors to be involved in data analysis in research projects. Their experience has been that giving public contributors large amounts of text to read is not the best use of their time and experience. They have recommended that a better approach would be for a researcher to meet with a group of users at the start of analysis, to discuss what to look out for. However, as another patient group that has been involved in analysis, we think differently. The approach we used was to be more fully involved in the project over a longer time period. Analysis tasks were broken down into stages to make it easier for those taking part. We found that this allowed us to take part fully without placing too much burden on us. We found that our approach was workable and successful and see no reason why it could not be applied in other circumstances. In this journal, Locock et al. have suggested that service users should not be overburdened with large amounts of data, and that eliciting users' reflections on their experience at the start of analysis and using this as a guide to direct researcher attention during the remainder of the process may work better. As public contributors that have been involved in analysis we suggest an alternative approach in this brief letter, based on our own experiences.


Mechanisms of Nucleosome Reorganization by PARP1.
Poly(ADP-ribose) polymerase 1 (PARP1) is an enzyme involved in DNA repair, chromatin organization and transcription. During transcription initiation, PARP1 interacts with gene promoters where it binds to nucleosomes, replaces linker histone H1 and participates in gene regulation. However, the mechanisms of PARP1-nucleosome interaction remain unknown. Here, using spFRET microscopy, molecular dynamics and biochemical approaches we identified several different PARP1-nucleosome complexes and two types of PARP1 binding to mononucleosomes: at DNA ends and end-independent. Two or three molecules of PARP1 can bind to a nucleosome depending on the presence of linker DNA and can induce reorganization of the entire nucleosome that is independent of catalytic activity of PARP1. Nucleosome reorganization depends upon binding of PARP1 to nucleosomal DNA, likely near the binding site of linker histone H1. The data suggest that PARP1 can induce the formation of an alternative nucleosome state that is likely involved in gene regulation and DNA repair.


Structure and expression of the human histamine H4-receptor gene.
We report the characterization by genomics-based approach of the human H4-receptor gene structure. The H4-receptor gene have been mapped by radiation hybrid experiments (Gene Bridge 4) on chromosome 18q11.2, between the AFMBB11WH5 and CHLC.GATA85D10 markers. The H4-receptor gene spans more than 21 kbp and contains three exons separated by two large introns (>7 kbp). RT-PCR analysis showed that the H4-receptor gene encoded a 3.7 kb mRNA which did not seem to be alternatively spliced within its coding region. The H4-receptor transcripts were found to be highly expressed in peripheral tissues implicated in inflammatory responses such as leukocytes, spleen, lung, and liver. In addition, low expression level of the H4-receptor mRNA was also detected in several human brain regions. Analysis of the 5'-flanking region of the H4-receptor gene did not reveal the existence of canonical TATA or CAAT-box. However, several putative regulatory elements mediating TNFalpha or IL-6-stimulated transcriptional activation were detected. The uteroglobin promoter binding factor, known to mediate anti-inflammatory response of uteroglobin, in the lung, was also found in this region. Thus, the description of the H4-receptor gene promoter region will facilitate the elucidation of its transcriptional control by factors secreted during inflammatory responses.


Terminal Oxidases of Chlorella pyrenoidosa.
In studies of the kinetics of oxygen uptake by glucose-stimulated Chlorella pyrenoidosa, two terminal oxidases could be distinguished. The cytochrome oxidase of Chlorella has a Km (O(2)) of 2.1 +/- 0.3 mum, while the second oxidase has a Km (O(2)) of 6.7 +/- 0.5 mum, and a maximum capacity about one-quarter of that of the cytochrome system. The identity of the second oxidase is unknown, but it is not inhibited by carbon monoxide, 1 mm cyanide, 0.1 mm thiocyanate, or 1 mm 8-hydroxyquinoline. In fresh cultures, the second oxidase accounts for at most 35% of the total oxygen uptake.


Altered Mucus Barrier Integrity and Increased Susceptibility to Colitis in Mice upon Loss of Telocyte Bone Morphogenetic Protein Signalling.
FoxL1+-Telocytes (TCFoxL1+) are subepithelial cells that form a network underneath the epithelium. We have shown that without inflammatory stress, mice with loss of function in the BMP signalling pathway in TCFoxL1+ (BmpR1aΔFoxL1+) initiated colonic neoplasia. Although TCFoxL1+ are modulated in IBD patients, their specific role in this pathogenesis remains unclear. Thus, we investigated how the loss of BMP signalling in TCFoxL1+ influences the severity of inflammation and fosters epithelial recovery after inflammatory stress. BmpR1a was genetically ablated in mouse colonic TCFoxL1+. Experimental colitis was performed using a DSS challenge followed by recovery steps to assess wound healing. Physical barrier properties, including mucus composition and glycosylation, were assessed by alcian blue staining, immunofluorescences and RT-qPCR. We found that BmpR1aΔFoxL1+ mice had impaired mucus quality, and upon exposure to inflammatory challenges, they had increased susceptibility to experimental colitis and delayed healing. In addition, defective BMP signalling in TCFoxL1+ altered the functionality of goblet cells, thereby affecting mucosal structure and promoting bacterial invasion. Following inflammatory stress, TCFoxL1+ with impaired BMP signalling lose their homing signal for optimal distribution along the epithelium, which is critical in tissue regeneration after injury. Overall, our findings revealed key roles of BMP signalling in TCFoxL1+ in IBD pathogenesis.


A girl with an atypical form of ataxia telangiectasia and an additional de novo 3.14 Mb microduplication in region 19q12.
A 9-year-old girl born to healthy parents showed manifestations suggestive of ataxia telangiectasia (AT), such as short stature, sudden short bouts of horizontal and rotary nystagmus, a weak and dysarthric voice, rolling gait, unstable posture, and atactic movements. She did not show several cardinal features typical of AT such as frequent, severe infections of the respiratory tract. In contrast, she showed symptoms not generally related to AT, including microcephaly, profound motor and mental retardation, small hands and feet, severely and progressively reduced muscle tone with slackly protruding abdomen and undue drooling, excess fat on her upper arms, and severe oligoarthritis. A cranial MRI showed no cerebellar hypoplasia and other abnormalities. In peripheral blood samples she carried a de novo duplication of 3.14 Mb in chromosomal region 19q12 containing six annotated genes, UQCRFS1, VSTM2B, POP4, PLEKHF1, CCNE1, and ZNF536, and a de novo mosaic inversion 14q11q32 (96% of metaphases). In a saliva-derived DNA sample only the duplication in 19q12 was detected, suggesting that the rearrangements in blood lymphocytes were acquired. These findings reinforced the suspicion that she had AT. AT was confirmed by strongly elevated serum AFP levels, cellular radiosensitivity and two inherited mutations in the ATM gene (c.510_511delGT; paternal origin and c.2922-50_2940del69; maternal origin). This case suggest that a defective ATM-dependent DNA damage response may entail additional stochastic genomic rearrangements. Screening for genomic rearrangements appears indicated in patients suspected of defective DNA damage responses.


Random-walk model of the sodium-glucose transporter SGLT2 with stochastic steps and inhibition.
Random-walk models are frequently used to model distinct natural phenomena such as diffusion processes, stock-market fluctuations, and biological systems. Here, we present a random-walk model to describe the dynamics of glucose uptake by the sodium-glucose transporter of type 2, SGLT2. Our starting point is the canonical alternating-access model, which suggests the existence of six states for the transport cycle. We propose the inclusion of two new states to this canonical model. The first state is added to implement the recent discovery that the Na+ion can exit before the sugar is released into the proximal tubule epithelial cells. The resulting model is a seven-state mechanism with stochastic steps. Then we determined the transition probabilities between these seven states and used them to write a set of master equations to describe the time evolution of the system. We showed that our model converges to the expected equilibrium configuration and that the binding of Na+and glucose to SGLT2 in the inward-facing conformation must be necessarily unordered. After that, we added another state to implement inhibition in the model. Our results reproduce the experimental dependence of glucose uptake on the inhibitor concentration and they reveal that the inhibitors act by decreasing the number of available SGLT2s, which increases the chances of glucose escaping reabsorption.


Peer support to decrease diabetes-related distress in patients with type 2 diabetes mellitus: design of a randomised controlled trial.
Many type 2 diabetes mellitus patients face difficulties self-managing their illness, which can lead to high levels of diabetes-related distress. Diabetes distress may be decreased by peer support, as peers understand and have dealt with similar problems, and can help motivate each other. A recent systematic review concluded that evidence of benefits of peer support in patients with type 2 diabetes mellitus is too inconsistent due to weak theoretical foundation of the interventions. This study describes the design of a trial evaluating the effectiveness of a group-based, peer support programme with a strong theoretical foundation on diabetes-related distress in type 2 diabetes patients. This is a parallel group randomised controlled trial of a six session group-based peer support intervention, delivered by peer leaders and group psychotherapists, compared with one educational meeting on diabetes. At least 152 patients with a type 2 diabetes duration of three years or more and between 50 and 70 years of age, recruited via their general practitioner, will be randomised to receive the peer support intervention or one educational meeting. The intervention is developed in line with three key stages of research development of the Medical Research Council framework. The primary outcome measure for this study is diabetes-related distress. Secondary outcomes include self-management behaviour, well-being and health-related quality of life. Perceived social support is a process measure. Outcomes will be measured one month before, and 6, and 12 months after the intervention by means of self-reported questionnaires. Analysis will be on an intention-to-treat basis. This article contains a description of the design of a study that will investigate the effect of a group-based, peer support intervention on diabetes-related distress in type 2 diabetes patients. The intervention was developed in recognition of the limited evidence, and the importance of a theoretical foundation and its implementation. Findings will contribute to knowledge in the field of peer support and patient-important outcomes in type 2 diabetes patients. Dutch Trial Registry: NTR3474.


4-Methylthio-3-butenyl isothiocyanate (raphasatin) exerts chemopreventive effects against esophageal carcinogenesis in rats.
To examine the effects of 4-methylthio-3-butenyl isothiocyanate on esophageal carcinogenesis, male 6-week-old F344 rats were subcutaneously injected with 0.5 mg/kg body weight N-nitrosomethylbenzylamine three times per week for 5 weeks and fed a diet supplemented with 80 ppm 4-methylthio-3-butenyl isothiocyanate, equivalent to 6.05 mg/kg body weight/day for the initiation stage, 4.03 mg/kg body weight/day for the promotion stage, or 4.79 mg/kg body weight/day for all stages. Although the incidence of lesions was not affected by 4-methylthio-3-butenyl isothiocyanate treatment, the multiplicity of squamous cell papilloma in the esophagus was significantly decreased in rats in the 4-methylthio-3-butenyl isothiocyanate initiation stage group (1.13 ± 0.74), 4-methylthio-3-butenyl isothiocyanate promotion stage group (1.47 ± 0.99), and 4-methylthio-3-butenyl isothiocyanate all stage group (1.47 ± 1.13) as compared with rats treated with N-nitrosomethylbenzylamine alone (3.00 ± 1.46). Immunohistochemical analysis revealed that 4-methylthio-3-butenyl isothiocyanate induced apoptosis, suppressed cell proliferation, and increased p21 expression when administered in the promotion phase. These modifying effects were not observed in the rats treated with 4-methylthio-3-butenyl isothiocyanate alone. Our results indicated that 4-methylthio-3-butenyl isothiocyanate may exert chemopreventive effects against N-nitrosomethylbenzylamine-induced esophageal carcinogenesis in rats.


Dual topology of the large envelope protein of duck hepatitis B virus: determinants preventing pre-S translocation and glycosylation.
The biosynthesis and topology of the large envelope protein (L protein) of hepadnaviruses was investigated using the duck hepatitis B virus (DHBV) model, which also allows the study of hepadnavirus morphogenesis in experimentally infected hepatocytes. Results from proteolysis of virus particles and from the analysis of topology and posttranslational modification of L chains synthesized in vivo or in a cell-free system both support the presence of a mixed population of L-protein molecules with their N-terminal pre-S domain located either inside or outside the virus particle. During L biosynthesis and DHBV morphogenesis, pre-S, together with the neighboring transmembrane domain (TM-I), initially remained cytoplasmically disposed and was translocated only posttranslationally. Delayed pre-S translocation into a post-endoplasmic reticulum compartment is also indicated by the absence of glycosylation at a modification-competent pre-S glycosylation site. Major features of L-protein biosynthesis and of the resulting dual topology appear to be conserved between avian and mammalian hepadnaviruses, supporting the model that pre-S domains function in part either as an internal matrix for capsid envelopment or externally as a ligand for cellular receptor binding. However, differences in the mechanisms controlling pre-S translocation were revealed by the results of mutational analyses identifying and characterizing cis-acting determinants in pre-S that delay its cotranslational translocation. Our data from DHBV demonstrate the negative influence of a cluster of positively charged amino acid residues next to TM-I, a motif that is conserved among the avian but absent from mammalian hepadnaviruses. Additional control elements, which are apparently shared between both virus groups and which may serve in chaperone binding, were mapped by deletion analysis in the central part of pre-S.


Thidiazuron suppresses breast cancer via targeting miR-132 and dysregulation of the PI3K-Akt signaling pathway mediated by the miR-202-5p-PTEN axis.
Chemo-resistance and metastasis are the most common causes of breast cancer recurrence and death. Thidiazuron (TDZ) is a plant growth regulator (phytohormone) whose biological effects on humans and animals has not yet been determined. In this study, we investigated the anticancer activity of this phytohormone on the drug resistant-triple negative breast cancer cell line MDA-MB-231. Treatment of the breast cancer cells with TDZ (1-50 μmol/L) caused more stressful environment and induced a significant increase in active caspase-positive cells. In addition, TDZ treatment (5 and 10 μmol/L) significantly attenuated the migration and the invasiveness of these highly metastatic cancer cells. Mechanistically, TDZ reduces cancer progression and invasiveness by targeting miR-202-5p, which stimulates the expression of phosphatase and tensin homolog (PTEN), the tumor suppressor that downregulates the PI3K-Akt signaling pathway. Treatment with TDZ significantly upregulates miRNA-132, the suppressor of breast cancer proliferation, which is also implicated in dysregulation of the TEN-Akt-NFκB signaling pathway. Interestingly, our molecular docking analysis revealed a potential non-covalent interaction between TDZ and Akt, PTEN, and PI3K. These findings suggest that TDZ suppresses breast cancer metastasis by targeting miRNA-132, the miR-202-5p-PTEN axis, and the PI3K-Akt signaling pathway downstream.


Ethical considerations in the prevention and management of genetic disorders with special emphasis on religious considerations.
Genetic diseases include not only single gene disorders, but multifactorial, somatic cell genetic disorders, mitochondrial and even chromosomal. One in 4 adults will suffer from a multifactorial or a somatic cell genetic disease. The common diseases in the community have a hereditary component namely diabetes mellitus, hypertension, ischemic heart diseases and many types of cancer. Even monogenic diseases which affect a small number of the newborns (2%-3%), have a greater impact on childhood diseases up to age 15 years. Therefore, it is imperative to scrutinize the available methods of prevention and management of genetic disorders, their ethical implications, and since east Mediterranean region is mainly occupied by Arabs and muslims, religious considerations become of paramount importance. Islam differs from many other religions in providing a complete code of life, which encompasses the secular with spiritual, the mundane with the celestial and hence forms the basis of the ethical, moral and even juridical attitudes and laws towards any problem or situation. Islamic teachings carry a great deal of instructions for health promotion and disease prevention including hereditary and genetic disorders. This review discusses how the Islamic teachings play an important role in the prevention and management of genetic disorders and the type of ethical implications involved in such management namely premarital medical examination, the question of consanguinity, the genetic counseling, the question of preimplantation diagnosis, the question of abortion and the offering of alternative ways of reproduction.


Molecular Characterization and Phylogenetic Analysis of Earthworm Species Collected from Different Soil Habitats of Poonch Division Azad Jammu and Kashmir Pakistan.
This study aims to analyze molecular characterization and phylogenetic analysis of earthworm species collected from different soil habitats of Poonch division Azad Kashmir Pakistan by using CO1 gene partial sequencing methodology. Samples gathered randomly from 18 study sites (127 localities) by digging and hand sorting methods were preserved in pure ethanol at -20°C. The modified CTAB (Cetyltrimethyl ammonium bromide) method extracted high quality DNA from region of representative earthworm's caudal region. This extracted DNA was used to amplify the 700 bp partial region of the cytochrome oxidase I (COI) gene with LCO1490 and HCO2198 universal primers. All of the obtained amplified gene sequences were aligned, edited and analyzed using MEGA X software to characterize different species of earthworms. Thirty-eight (38) Barcoding sequences belonging to 11 different strains of earthworms were successfully generated. Their phylogenetic analysis revealed that 7 Barcoding sequences gave maximum similarity with the available online database, while the rest of the 4 sequences gave lower similarity than the maximum threshold level. The collected DNA barcode sequences were also clustered together by the maximum likelihood method and the resultant phylogenetic tree revealed they belong to different family lineages. Moreover the identified earthworm species have a close evolutionary link with the earthworm fauna of south and central Asia instead of Europe, which might be due to similar climate of both regions.


Hypertonic saline up-regulates A3 adenosine receptor expression of activated neutrophils and increases acute lung injury after sepsis.
Hypertonic saline resuscitation reduces tissue damage by inhibiting polymorphonuclear neutrophils. Hypertonic saline triggers polymorphonuclear neutrophils to release adenosine triphosphate that is converted to adenosine, inhibiting polymorphonuclear neutrophils through A2a adenosine receptors. Polymorphonuclear neutrophils also express A3 adenosine receptors that enhance polymorphonuclear neutrophil functions. Here we investigated whether A3 receptors may diminish the efficacy of hypertonic saline in a mouse model of acute lung injury. Randomized animal study and laboratory investigation. University research laboratory. The effect of A3 receptors on the efficacy of hypertonic saline resuscitation was assessed in A3 receptor knockout and wild-type mice. Animals were treated with hypertonic saline (7.5% NaCl, 4 mL/kg) before or after cecal ligation and puncture, and acute lung injury and mortality were determined. The effect of timing of hypertonic saline exposure on A3 receptor expression and degranulation was studied in vitro with isolated human polymorphonuclear neutrophils. Treatment of human polymorphonuclear neutrophils with hypertonic saline before stimulation with formyl methionyl-leucyl-phenylalanine inhibited A3 receptor expression and degranulation, whereas hypertonic saline-treatment after formyl methionyl-leucyl-phenylalanine-stimulation augmented A3 receptor expression and degranulation. Acute lung injury in wild-type mice treated with hypertonic saline after cecal ligation and puncture was significantly greater than in wild-type mice pretreated with hypertonic saline. This aggravating effect of delayed hypertonic saline-treatment was absent in A3 receptor knockout mice. Similarly, mortality in wild-type mice with delayed hypertonic saline-treatment was significantly higher (88%) than in animals treated with hypertonic saline before cecal ligation and puncture (50%). Mortality in A3 receptor knockout mice remained only 50% regardless of timing of hypertonic saline administration. Polymorphonuclear neutrophil A3 receptors expression determines whether hypertonic saline resuscitation inhibits or aggravates polymorphonuclear neutrophil-induced acute lung injury. These findings suggest that A3 antagonists could improve the efficacy of hypertonic saline resuscitation by reducing side effects in patients whose polymorphonuclear neutrophils are activated before hypertonic saline treatment.


Strain engineering, efficient excitonic photoluminescence, and exciton funnelling in unmodified MoS2 nanosheets.
We established locally varying strain fields in unmodified MoS2 nanosheets. The approach relies on dry release in place of multilayer MoS2 on textured Si substrates. By this process we demonstrated intense photoluminescence, a ∼70 meV decrease of the transition energy, and exciton funneling in ∼4 nm-thick MoS2 films.


The Telomere/Telomerase System in Chronic Inflammatory Diseases. Cause or Effect?
Telomeres are specialized nucleoprotein structures located at the end of linear chromosomes and telomerase is the enzyme responsible for telomere elongation. Telomerase activity is a key component of many cancer cells responsible for rapid cell division but it has also been found by many laboratories around the world that telomere/telomerase biology is dysfunctional in many other chronic conditions as well. These conditions are characterized by chronic inflammation, a situation mostly overlooked by physicians regarding patient treatment. Among others, these conditions include diabetes, renal failure, chronic obstructive pulmonary disease, etc. Since researchers have in many cases identified the association between telomerase and inflammation but there are still many missing links regarding this correlation, the latest findings about this phenomenon will be discussed by reviewing the literature. Our focus will be describing telomere/telomerase status in chronic diseases under the prism of inflammation, reporting molecular findings where available and proposing possible future approaches.


Graphene encapsulated and SiC reinforced silicon nanowires as an anode material for lithium ion batteries.
Anode materials play a key role in the performance, in particular the capacity and lifetime, of lithium ion batteries (LIBs). Silicon has been demonstrated to be a promising anode material due to its high specific capacity, but pulverization during cycling and formation of an unstable solid-electrolyte interphase limit its cycle life. Herein, we show that anodes consisting of an active silicon nanowire (Si NW), which is surrounded by a uniform graphene shell and comprises silicon carbide nanocrystals, are capable of serving over 500 cycles in half cells at a high lithium storage capacity of 1650 mA h g(-1). In the anodes, the graphene shell provides a highly-conductive path and prevents direct exposure of Si NWs to electrolytes while the SiC nanocrystals may act as a rigid backbone to retain the integrity of the Si NW in its great deformation process caused by repetitive charging-discharging reactions, resulting in a stable cyclability.


Fracture of the humeral condyles in children: 49 cases evaluated after 18-45 years.
We evaluated 49 children with fracture of the humeral condyles 18-45 years after the injury. 20 fractures with a displacement of 2-1 0 mm with no tilting of the osteochondral fragment had been treated without reduction and with good results. 16 fractures with marked displacement and tilting of the osteochondral fragment had been treated surgically, with good results. 13 patients had been treated for old, displaced fractures both operatively and nonoperatively, with poor results. Nonunion developed in 4 cases and aseptic necrosis in 6. Arthrosis of the elbow was found in cases complicated by aseptic necrosis and nonunion or in old fractures when resection of the humeral condyle was done, but it was never observed in uncomplicated fractures.


Near full-length genome characterization of a new CRF01_AE/CRF08_BC recombinant transmitted between a heterosexual couple in Guangxi, China.
Human immunodeficiency virus type 1 (HIV-1) subtype CRF01_AE is transmitted mainly by sexual activity in Guangxi, southwestern China. Other subtypes, including CRF07_BC, CRF08_BC, and subtype B, are also prevalent in this region. Cocirculation of multiple subtypes, as well as a high rate of drug use, creates favorable conditions for the emergence of recombinant viruses in Guangxi. In the present study, we identified a new HIV-1 unique recombinant form (CRF01_AE /08BC) transmitted from the infected index patient to his seronegative sexual partner. This is the first near full-length genome characterization of a CRF01_AE /08BC recombinant virus in Guangxi, and provides an important basis for future analysis on potential new recombinant transmission events.


[Adjuvant chemotherapy in breast cancer. Report and commentary on the NIH Consensus Development Conference, Bethesda, Maryland, U.S. 9-11 September, 1985].
Adjuvant chemo- and endocrine treatment in breast cancer are effective treatment modalities. However, the cure rate in this disease is still not satisfying. Using prospective clinical trials further treatment procedures should be evaluated. Based on data presented at the 1985 Consensus Development Conference, treatment recommendations can be made for patients, who are not willing to participate in clinical trials: Regardless of steroid hormone receptor status combination chemotherapy has proven significant effectiveness in premenopausal patients with axillary node metastases, however in patients without nodal involvement this treatment is generally not recommended. For patients with receptor-negative and/or undifferentiated carcinomas chemotherapy should be considered. Postmenopausal patients with axillary node metastases and receptor-positive tumours should be treated with tamoxifen. In those with positive nodes and negative receptors chemotherapy may be considered. There is no indication for routine adjuvant chemotherapy in postmenopausal patients with negative nodes regardless of hormone receptor levels.


Distribution of mercury in rabbits subchronically exposed to low levels of radiolabeled methyl mercury.
The metabolism of methyl mercury (MeHg) has been studied in rabbits administered 203Hg-labeled methyl mercuric chloride, 0.125 mumol/kg body weight, twice a week for 9 weeks, by intravenous injection. Twelve weeks after cessation of treatment, about 54% of the administered dose had been excreted in faeces and 5% in urine. After one week, the highest concentration of 203Hg was found in fur (8.6 nmol Hg/g). Substantially lower concentrations were found in kidney (2.5 nmol/g), liver (0.9 nmol/g), brain (0.4 nmol/g), muscle (0.3 nmol/g) and blood (0.1 nmol/g). The rate of elimination of 203Hg from brain, muscle and blood was faster (t1/2 about 12 days) than that from kidney and liver (t1/2 about 28 days). The relative amount of inorganic Hg in kidney and liver increased with time after cessation of treatment. The highest fractions were 85 and 70%, respectively. In brain, no significant demethylation of MeHg could be detected.


Evidence that apoptosis of activated T cells occurs in spontaneous tolerance of liver allografts and is blocked by manipulations which break tolerance.
Fully allogeneic liver grafts from piebald virol glaxo to dark agouti rats are spontaneously tolerated, whereas kidney transplants between these strains are rejected. Liver tolerance is broken by donor irradiation or peritransplant corticosteroid treatment of recipient rats, both of which interfere with the activation of recipient cells. In this study we used a combination of immunohistochemical staining, reverse transcription-polymerase chain reaction, and terminal deoxynucleotide transferase-mediated dUTP nick end labeling and Annexin-V apoptosis assays to compare donor cell migration, cytokine profiles, and leukocyte apoptosis in grafts and lymphoid organs from tolerant liver and rejecting kidney recipients. We then examined the effect on apoptosis of treatments which abrogate liver tolerance. Liver transplantation in this tolerant strain combination is accompanied by rapid migration of many passenger leukocytes to the recipient spleen and lymph node, concurrent with a marked but transient increase in the amount of mRNA for the cytokines interleukin-2 and interferon-gamma. Apoptotic cells appear promptly in the spleen, their numbers reaching a peak 2 days earlier than has been previously shown for the graft infiltrate. Both CD4+ and CD8+ T cells undergo apoptosis and apoptotic cells are most concentrated among CD25+ T cells. In contrast, renal transplant rejection is associated with limited donor cell migration to lymphoid tissues and significantly less up-regulation of interleukin-2 and interferon-gamma in the spleen. Few apoptotic cells are detected in spleen or graft infiltrate during rejection, whereas apoptotic renal tubular and glomerular cells are found from day 5. Either recipient steroid treatment or donor irradiation significantly reduced the number of apoptotic cells in liver graft infiltrates and recipient spleen. Taken together, these findings suggest that a mechanism akin to activation-induced cell death, with apoptosis of alloreactive recipient cells may be responsible for the induction of spontaneous liver transplant tolerance.


Longitudinal Changes in the Total Knee Joint Moment After Anterior Cruciate Ligament Reconstruction Correlate With Cartilage Thickness Changes.
This study investigated associations between changes in the total joint moment (TJM) at the knee and changes in cartilage thickness after anterior cruciate ligament reconstruction (ACLR). Seventeen subjects (five males; age: 29.6 ± 7.3 years) with unilateral ACLR underwent gait analysis and magnetic resonance imaging at baseline (2.2 ± 0.3 years post-ACLR) and at long-term follow-up (7.7 ± 0.7 years post-ACLR). Knee loading was assessed using the TJM, and differences in loading were analyzed using repeated measures analysis of variance. Pearson correlation coefficients assessed associations between changes in TJM and changes in (medial-to-lateral) M/L femoral cartilage thickness ratios in the ACLR limb. Bilaterally, there was no significant change in the magnitude of the TJM first peak (TJM1), however, there was a significant increase in the percent contribution of the knee flexion moment (KFM) (p < 0.001) and decrease in the percent contribution of the knee adduction moment (KAM) to TJM1 (p < 0.001). The change in the percent contributions of KFM and KAM to TJM1 were associated with changes in M/L femoral cartilage thickness in the ACLR limb. Specifically, subjects with smaller increases in KFM contribution (R = 0.521, p = 0.032) and smaller decreases in KAM contribution (R = -0.521, p = 0.032) had a reduction in the M/L ratio in the central femoral subregion over the follow-up period, with similar trends in the external femoral subregion. The study results provide new insight into changes in the loading environment at the knee joint prospectively following ACL reconstruction and give evidence that there are modifiable gait metrics that are associated with cartilage changes after ACLR. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1546-1554, 2019.


Community development and preventive work.
The theoretical frame of reference in connection with prevention, some theoretical approaches, and the practical consequences of giving priority to prevention are discussed. The following points are stressed: that one must expand the theoretical frame of reference of prevention to include theory on local community, social networks and concepts of mutuality and self-supporting processes that preventive work is most efficient when it is developed in the form of fruitful interaction between primary intervention and selective intervention that giving priority to preventive work rather than implementing continuous expansion of institutions and fields of administration involves changes in the ones that already exist.