Retrospective analysis of the effects of low-dose, high frequency human growth hormone on serum lipids and prostate specific antigen.
Background. Elevated serum total cholesterol (TC) and triglycerides (TG) are risk factors for atherosclerosis and ischemic heart disease. Adult growth hormone deficiency (AGHD) is associated with elevated TC and TG. Many treatment protocols for AGHD use relatively high doses of growth hormone (GH) given at low frequency, which is associated with increased incidences of edema, joint pains, and carpal tunnel syndrome. We have treated > 2200 patients using a low-dose high frequency (LDHF) dosing regimen of GH which results in similar beneficial subjective responses, and fewer of the side-effects associated with the higher-dosage treatment at a substantial cost savings. Clinically, in addition to increased insulin-like growth factor I (IGF-I), we observed lower TG and TC levels and no elevation of prostate specific antigen levels in treated patients. Methods. A retrospective analysis of IGF-I, TG, TC, and PSA data from our patient population was performed to test our hypothesis that positive objective responses of IGF-I, TG, and TC occur and that elevation of PSA does not occur in response to LDHF dosing regimen of GH. The mean duration of treatment of the analyzed data ranged from 181 to 259 days. Results. The mean plasma IGF-I level rose significantly (p<.00001) to a level 37% greater than baseline with treatment. TC and TG decreased significantly (p<.001) in those patients with elevated baseline values, and did not change significantly in those with normal baseline values. PSA concentrations decreased non-significantly during treatment, and few cases of edema, joint pain, or carpal tunnel were reported. Conclusions. Treatment of AGHD using the LDHF dosing regimen of GH resulted in significant increases in IGF-I, significant reductions in TC and TG levels in patients with elevated baseline values, no increase in PSA concentrations, and fewer side effects than other dosing regimens.


Reflections on the declining ability of the Salmonella assay to detect rodent carcinogens as positive.
It is suggested that urgent attempts should be made to define and gain general agreement for the existence of two classes of animal carcinogen, those which are genotoxic and those which are not. In the absence of such a step, attempts to validate in vivo genotoxicity assays, and to derive a meaningful structure-activity database for chemical carcinogenesis, will be frustrated. These suggestions are supported by the preliminary findings of a detailed analysis of the carcinogen database accrued by the United States National Toxicology Program. The possibility that many non-genotoxic carcinogens should be regarded as tumour-promoting agents is considered.


A Comparison of Medical Comorbidities, Psychosocial, and Sexual Well-being in an Online Cross-Sectional Sample of Women Experiencing Persistent Genital Arousal Symptoms and a Control Group.
Persistent genital arousal disorder (PGAD) is characterized by symptoms of distressing physiological sexual arousal (Persistent genital arousal [PGA] symptoms such as genital vasocongestion, sensitivity, or both) that occur in the absence of sexual desire. There continues to be a lack of systematic research on this condition. Little is known about the common medical comorbidities and psychological, sexual, or relationship well-being of individuals who experience PGA symptoms. To compare these biopsychosocial factors in an age-matched sample of women with and without symptoms of PGA. A secondary aim was to examine what symptom factors (associated distress, symptom severity) and cognitive factors (eg, catastrophizing of vulvar sensations) were associated with psychosocial outcomes in women with symptoms of PGA. Age-matched samples of women with (n = 72) and without (n = 72) symptoms of PGA completed a comprehensive online survey. Participants self-reported their medical histories and completed validated measures of psychosocial functioning (depressive and anxiety symptoms, catastrophizing of vulvar sensations, sexual functioning and distress, and relationship functioning). Women with symptoms of PGAD reported significantly greater depressive and anxiety symptoms, sexual distress, and suicidal ideation, as well as significantly poorer relationship functioning than women without PGA symptoms. Catastrophizing of vulvar sensations was related to PGA symptom ratings (greater severity, distress) and psychosocial outcomes (greater depression, anxiety, and sexual distress). The results of this study highlight medical and psychosocial difficulties associated with PGA symptoms, which should be assessed and addressed as essential components of treatment. This study seeks to address the paucity of research on the well-being of women with PGA symptoms by undertaking a comparison of age-matched samples using validated questionnaires. This study is limited by its self-report, cross-sectional design. PGA symptoms are associated with significant health and psychological difficulties. These results highlight the need for continued research in this area to improve identification and treatment for this population. Jackowich RA, Poirier É, Pukall CF. A Comparison of Medical Comorbidities, Psychosocial, and Sexual Well-being in an Online Cross-Sectional Sample of Women Experiencing Persistent Genital Arousal Symptoms and a Control Group. J Sex Med 2020;17:69-82.


Analytical techniques for charactering radioactive particles deposited in the environment.
Since 1945, a series of nuclear and radiological sources have contributed to the release of radioactive particles containing refractory elements into the environment. Several years of research have demonstrated that the particle composition will depend on the source, while the release scenarios will influence particle properties of relevance for environmental transfer. Radioactive particles can also carry sufficient amount of radioactivity (MBq) and represent point sources of radiological concern. Most radiological assessment models, however, are based on bulk concentrations, assuming that radionuclides in the environment are evenly distributed. In contrast, radioactive particles and thereby doses are unevenly distributed, while leaching of radionuclides from particles prior to measurements can be partial, potentially leading to underestimation of inventories. For areas affected by particle contamination, information on particle characteristics controlling the particle weathering rates and remobilization of particle associated radionuclides will therefore be essential to reduce the overall uncertainties of the impact assessments. The present paper will focus on analytical strategies, from screening techniques applicable for identifying hot spots in the field, fractionation techniques and single particle extraction techniques as a preparatory mean to apply non-destructive solid state speciation techniques, till leaching techniques applied sequentially to obtain information on binding mechanisms, mobility and potential bioavailability. Thus, a combination of techniques should be utilized to characterize radioactive particles in order to improve environmental assessments for areas affected by radioactive particle fallout.


Identifying the geographic distribution pattern of venomous snakes and regions of high snakebite risk in Iran.
We describe species richness patterns of venomous snakes in Iran in order to produce snakebite risk prediction maps and identify gaps in regional health care centers capable of managing snakebites. We digitized distribution maps from the literature, Global Biodiversity Information Facility (GBIF), and the results of our own field studies of 24 terrestrial venomous snake species (including 4 endemic to Iran). Species richness patterns were associated with eight environmental factors. The variables have been extracted from the WorldClim dataset (bio12 = annual precipitation, bio15 = precipitation seasonality, bio17 = precipitation of the driest quarter, bio2 = mean diurnal range, bio3 = isothermality (bio2/bio7), bio4 = temperature seasonality, bio9 = mean temperature of the driest quarter and slope). Based on spatial analyses, species richness in Iran is highly affected by three environmental variables (bio12, 15, and 17) associated with precipitation. The relationship patterns among these predictors and species richness were strong and linear. The hotspot regions for venomous snakes species are concentrated on the western to southwestern and north to northeastern regions of Iran, which is partially consistent with the known Irano-Anatolian biodiversity hotspot. Because of the high number of endemic species and climatic conditions on the Iranian Plateau, the venoms of snakes distributed in those areas may contain novel properties and components.


Musical hallucinations: prevalence in psychotic and nonpsychotic outpatients.
Musical hallucinations have been considered a rare manifestation of psychotic states or brain and hearing abnormalities. However, an obsessive-compulsive disorder (OCD) assessment tool refers to musical hallucinations and our preliminary study showed that about one third of OCD patients experienced musical hallucinations. To elucidate the lifetime prevalence of musical hallucinations among psychotic and nonpsychotic psychiatric outpatients. Lifetime experience of musical hallucinations was examined with a specially designed structured interview in 190 consecutive outpatients with diagnoses of anxiety, affective, and schizophrenia disorders. Musical hallucinations occurred in more than one fifth of all diagnoses. The prevalence of musical hallucinations was highest in OCD patients (41%). Musical hallucinations were significantly more frequent with more comorbid disorders, and logistic regression revealed that this finding was mainly due to OCD combined with either social phobia or schizophrenia. Musical hallucinations are more common among psychiatric patients than previously reported and are more suggestive of OCD than of other mental disorders.


[The immediate results of treating patients with acute early postoperative intestinal obstruction].
We performed 58,938 operations on the abdominal organs. Three hundred and six (37.8%) patients developed early postoperative acute ileus. After its operative elimination, 22 (7.2%) patients required performance of a reoperation. Ninety (29.4%) patients died. Of them in 72, death was caused by peritonitis, in 18--pneumonia, acute cardiovascular failure, impairement in cerebral circulation and pulmonary thromboembolism.


Radical appendectomy as an alternative to right colon resection in patients with epithelial appendiceal neoplasms.
Appendectomy is an extremely common surgical procedure usually performed for an inflammatory process within this organ. Upon occasion, the pathology within the appendix is a neoplastic process which requires definitive oncologic management. The optimal management strategies for appendiceal neoplasms were reviewed and pertinent literature critically evaluated. The technology for appendectomy for an inflammatory process and an appendectomy for a neoplastic process were compared and contrasted. A new surgical procedure called "radical appendectomy" was described and its merits for optimizing the management of an appendiceal neoplasm enumerated. The technology of radical appendectomy was described. The possible shortcomings that may be encountered in performing a new surgical methodology for appendectomy was presented and the results of a technically perfect radical appendectomy enumerated. The integration of a radical appendectomy with perioperative hyperthermic chemotherapy was described. When a malignancy exists as the cause of appendiceal pathology, the radical appendectomy will provide the maximal amount of information required for optimal decisions regarding patient management.


Application of Theranostics in Oncology.
In recent years, due to the development of nanotechnology new horizons in treatment and diagnosis of cancer open up. Development of nano-systems for simultaneous transfer of active substances and imaging of tumor regions gathers an important amount of scientific interest. This new category of nano-systems is called Theranostics. Theranostics methods can provide multiple benefits by inserting nanoparticles into the patient and using photodynamic therapy and pave the way for personalized medicine. The objective of this paper is to study the use and application of Theranostics in the diagnosis and treatment of cancer, in order to achieve personalized anticancer treatment. For this purpose, investigation of existing literature has been conducted using electronic databases, PubMed, Google Scholar and IEEE Xplore. In addition, there was a secondary research phase, using paper citations found during the first research phase. It has to be pointed out that nanoparticles are the basis of Theranostics, since, due to their properties, they provide the ability to display accurate imaging and provide diagnosis along with simultaneous treatment of diseases. Theranostics methods may be applied in treatment of esophageal cancer, prostate cancer, breast cancer, in treatment of actinic keratosis, actinic cheilitis and Bowen's disease and in treatment of basal cell epithelioma and macular degeneration. As a result, application of Theranostics can provide multiple benefits by inserting nanoparticles into the patient. This method is currently encountering many challenges, but continuation of research on the field is necessary not only for the improvement of the medical field and the healthcare techniques, but also for the creation of new treatment methods for patients with diseases that are incurable until now.


Exploring the impact and use of patients' feedback about their care experiences in general practice settings-a realist synthesis.
Policy encourages health care providers to listen and respond to feedback from patients, expecting that it will enhance care experiences. Enhancement of patients' experiences may not yet be a reality, particularly in primary health care settings. To identify the issues that influence the use and impact of feedback in this context. A realist synthesis of studies of the use of patient feedback within primary health care settings. Structured review of published studies between 1971 and January 2015. Eighteen studies were reported in 20 papers. Eleven studies reported patient survey scores as a primary outcome. There is little evidence that formal patient feedback led to enhanced experiences. The likelihood of patient feedback to health care staff stimulating improvements in future patients' experiences appears to be influenced predominantly by staff perceptions of the purpose of such feedback; the validity and type of data that is collected; and where, when and how it is presented to primary health care teams or practitioners and teams' capacity to change. There is limited research into how patient feedback has been used in primary health care practices or its usefulness as a stimulant to improve health care experience. Using a realist synthesis approach, we have identified a number of contextual and intervention-related factors that appear to influence the likelihood that practitioners will listen to, act on and achieve improvements in patient experience. Consideration of these may support research and improvement work in this area.


Purification and characterization of the heat-stable calmodulin-binding protein from the matrix of bovine heart mitochondria.
A heat-stable calmodulin binding protein was purified and characterized from the matrix of bovine heart mitochondria. It bound specifically to calmodulin in the presence of calcium, and strongly inhibited the stimulatory activity of calmodulin on phosphodiesterase. The estimated molecular weight of the calmodulin-binding protein was 61,000 dalton determined by SDS-polyacrylamide gel electrophoresis.


Heroes in crisis: Trauma centers should be screening for and intervening on posttraumatic stress in our emergency responders.
Emergency responders face a crisis of rising suicide rates, and many resist seeking help due to the stigma surrounding mental health. We sought to evaluate the feasibility of an urban trauma center to screen for posttraumatic stress (PTS) among emergency responders and to provide mental health services. Paramedics, firefighters, law enforcement, and corrections officers involved with patients in the trauma unit were asked to complete the Post-Traumatic Growth Inventory (PTGI) and Post-Traumatic Checklist for Diagnostic and Statistical Manual-5 (PCL-5). Additional factors known to affect PTS were correlated: occupation, age, sex, years of service, marital status, children, and pets. Willingness and barriers to seeking interventions for PTS were evaluated. A total of 258 responded: 36.7% paramedics, 40.2% law enforcement officers, 18.4% corrections officers, 0.8% firefighters, and 3.5% with multiple positions. Responders had a mean of 14.5 years of service (SD, 9.9 years). Mean PTGI and PCL-5 scores were 52.1 (SD, 25.1) and 17.2 (SD, 16.5), respectively. Overall, 24.7% had diagnostic PTS disorder with no difference seen in rates between professions. Of these, 80.7% had not sought care. Barriers included that they were not concerned (46%), did not recognize symptoms (24%), and were worried about consequences (20%). Concern over career advancement or losing one's job was the greatest barrier cited for seeking care. Among law enforcement, 47.7% were concerned that they would lose their ability to carry a firearm if they sought care for PTS. The PTGI score, divorce, and 46 years to 50 years were the only factors examined that correlated with increased PCL-5 score. There were 82.5% that felt the trauma center was the right place to screen and intervene upon PTS. Trauma centers are an ideal and safe place to both screen for PTS and offer mental health assistance. Comprehensive trauma-informed care by hospital-based intervention programs must expand to include emergency responders. Epidemiological study type, Level II.


Proteome analysis of formalin-fixed paraffin-embedded colorectal adenomas reveals the heterogeneous nature of traditional serrated adenomas compared to other colorectal adenomas.
Traditional serrated adenoma (TSA) remains the least understood of all the colorectal adenomas, although these lesions have been associated with a significant cancer risk, twice that of the conventional adenoma (CAD) and of the sessile serrated adenoma (SSA/P). This study was performed to investigate the proteomic profiles of the different colorectal adenomas to better understand the pathogenesis of TSA. We performed a global quantitative proteome analysis using the label-free quantification (LFQ) method on 44 colorectal adenoma (12 TSAs, 15 CADs, and 17 SSA/Ps) and 17 normal colonic mucosa samples, archived as formalin-fixed paraffin-embedded blocks. Unsupervised consensus hierarchical clustering applied to the whole proteomic profile of the 44 colorectal adenomas identified four subtypes: C1 and C2 were well-individualized clusters composed of all the CADs (15/15) and most of the SSA/Ps (13/17), respectively. This is consistent with the fact that CADs and SSA/Ps are homogeneous and distinct colorectal adenoma entities. In contrast, TSAs were subdivided into C3 and C4 clusters, consistent with the more heterogeneous entity of TSA at the morphologic and molecular levels. Comparison of the proteome expression profile between the adenoma subtypes and normal colonic mucosa further confirmed the heterogeneous nature of TSAs, which overlapped either on CADs or SSA/Ps, whereas CADs and SSAs formed homogeneous and distinct entities. Furthermore, we identified LEFTY1 a new potential marker for TSAs that may be relevant for the pathogenesis of TSA. LEFTY1 is an inhibitor of the Nodal/TGFβ pathway, which we found to be one of the most overexpressed proteins specifically in TSAs. This finding was confirmed by immunohistochemistry. Our study confirms that CADs and SSA/Ps form homogeneous and distinct colorectal adenoma entities, whereas TSAs are a heterogeneous entity and may arise from either SSA/Ps or from normal mucosa evolving through a process related to the CAD pathway. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Effects of glycerol on lung and liver tumor development.
Mice of several strains (A/J, SWR, MaMyJ, BALB/cByJ, 129J, and C57BL/6J) were treated with the carcinogens 3-methylcholanthrene, urethane, and 4-nitroquinoline 1-oxide and then given 1 or 5% glycerol in the drinking water for up to 4 months. Effects of glycerol on lung tumor multiplicity and incidence were evaluated. The effects of glycerol were variable, and in the majority of experiments glycerol failed to enhance tumor development in mouse lung. Analysis of cell kinetics did not show a proliferative response of alveolar or bronchiolar cells to glycerol. In rats, glycerol did not enhance the appearance of putative preneoplastic liver foci, and in C3H mice it did not increase the incidence of spontaneously occurring liver tumors. It is concluded that glycerol does not increase number or incidence of lung tumors in the mouse strains used, whether the animals are pretreated with a carcinogen or not. Glycerol does not affect liver tumor development.


Transthoracic echo-Doppler assessment of coronary microvascular function late after Kawasaki disease.
The goal of this study was to demonstrate that Doppler transthoracic echocardiography (TTE) may represent a valuable tool for the noninvasive demonstration of coronary microvascular dysfunction in children with previous Kawasaki disease (KD) by the measurement of coronary flow reserve (CFR) during cold pressor test (CPT). Twenty-five children with previous KD (mean follow-up, 4.6 +/- 2.6 years) were included in the study-16 with no evidence of coronary artery lesions (CALs(-)) by TTE and 9 with coronary aneurysms (CALs(+)). Seventeen age-matched healthy subjects were also recruited. Diastolic peak velocity was measured by pulsed Doppler both at rest (DPV(Rest)) and during CPT (DPV(CPT)) in the anterior descending artery. CFR was calculated as DPV(CPT)/DPV(Rest). KD patients demonstrated significantly higher values of DPV(Rest) (0.21 +/- 0.05 vs 0.13 +/- 0.01 cm/sec, p < 0.0001) and DPV(CPT) (0.33 +/- 0.07 vs 0.27 +/- 0.03 cm/sec, p < 0.005). CFR was reduced in KD compared to control subjects (1.5 +/- 0.4 vs 2.1 +/- 0.2, p < 0.0001). CFR was decreased in a similar manner in both CALs(+) patients (1.4 +/- 0.4, p = 0.002 vs controls) and CALs(-) patients (1.6 +/- 0.4, p < 0.0001 vs controls). Doppler TTE at rest and during CPT may represent a valuable modality for CFR evaluation in children with a history of KD. CFR is significantly reduced in KD patients independently of the presence of CALs.


Histochemical assessment on the cellular interplay of vascular endothelial cells and septoclasts during endochondral ossification in mice.
This study was aimed to verify the cellular interplay between vascular endothelial cells and surrounding cells in the chondro-osseous junction of murine tibiae. Many CD31-positive endothelial cells accompanied with Dolichos Biflorus Agglutinin lectin-positive septoclasts invaded into the hypertrophic zone of the tibial epiphyseal cartilage. MMP9 immunoreactive cytoplasmic processes of vascular endothelial cells extended into the transverse partitions of cartilage columns. In contrast, septoclasts included several large lysosomes which indicate the incorporation of extracellular matrices despite no immunopositivity for F4/80-a hallmark of macrophage/monocyte lineage. In addition, septoclasts were observed in c-fos-/- mice but not in Rankl-/- mice. Unlike c-fos-/- mice, Rankl-/- mice showed markedly expanded hypertrophic zone and the irregular shape of the chondro-osseous junction. Immunoreactivity of platelet-derived growth factor-bb, which involved in angiogenic roles in the bone, was detected in not only osteoclasts but also septoclasts at the chondro-osseous junction. Therefore, septoclasts appear to assist the synchronous vascular invasion of endothelial cells at the chondro-osseous junction. Vascular endothelial cells adjacent to the chondro-osseous junction possess endomucin but not EphB4, whereas those slightly distant from the chondro-osseous junction were intensely positive for both endomucin and EphB4, while being accompanied with ephrinB2-positive osteoblasts. Taken together, it is likely that vascular endothelial cells adjacent to the chondro-osseous junction would interplay with septoclasts for synchronous invasion into the epiphyseal cartilage, while those slightly distant from the chondro-osseous junction would cooperate with osteoblastic activities presumably by mediating EphB4/ephrinB2. Our original article demonstrated that vascular endothelial cells adjacent to the chondro-osseous junction would interplay with septoclasts for synchronous invasion into the epiphyseal cartilage, while those slightly distant from the chondro-osseous junction would cooperate with osteoblastic activities presumably by mediating EphB4/ephrinB2. (A figure that best represents your paper is Fig. 5c).


The predictive value of EEG reactivity by electrical stimulation and quantitative analysis in critically ill patients with large hemispheric infarction.
The intensive care of critically ill patients with large hemispheric infarction improves the survival rate. However, established prognostic markers for neurological outcome show variable accuracy. We aimed to assess the value of electrical stimulation and quantitative analysis of EEG reactivity for early prognostication in this critically ill population. We prospectively enrolled consecutive patients between January 2018 and December 2021. EEG reactivity was randomly performed by pain or electrical stimulation via visual and quantitative analysis. Neurological outcome within 6-month was dichotomized as good (modified Rankin Scale, mRS 0-3) or poor (mRS 4-6). Ninety-four patients were admitted, and 56 were included in the final analysis. EEG reactivity using electrical stimulation was superior to pain stimulation for good outcome prediction (visual analysis: AUC 0.825 vs. 0.763, P = 0.143; quantitative analysis: AUC 0.931 vs. 0.844, P = 0.058). The AUC of EEG reactivity by pain stimulation with visual analysis was 0.763, which increased to 0.931 by electrical stimulation with quantitative analysis (P = 0.006). When using quantitative analysis, the AUC of EEG reactivity increased (pain stimulation 0.763 vs. 0.844, P = 0.118; electrical stimulation 0.825 vs. 0.931, P = 0.041). EEG reactivity by electrical stimulation and quantitative analysis seems a promising prognostic factor in these critical patients.


Genome-directed isolation of the key nitrogen fixer Leptospirillum ferrodiazotrophum sp. nov. from an acidophilic microbial community.
Analysis of assembled random shotgun sequence data from a low-diversity, subsurface acid mine drainage (AMD) biofilm revealed a single nif operon. This was found on a genome fragment belonging to a member of Leptospirillum group III, a lineage in the Nitrospirae phylum with no cultivated representatives. Based on the prediction that this organism is solely responsible for nitrogen fixation in the community, we pursued a selective isolation strategy to obtain the organism in pure culture. An AMD biofilm sample naturally abundant in Leptospirillum group III cells was homogenized, filtered, and serially diluted into a nitrogen-free liquid medium. The resulting culture in the terminal dilution grew autotrophically to a maximum cell density of approximately 10(6) cells/ml, oxidizing ferrous iron as the sole energy source. 16S rRNA-internal transcribed spacer region clone library analysis confirmed that the isolate is a member of Leptospirillum group III and that the culture is axenic. We propose the name Leptospirillum ferrodiazotrophum sp. nov. for this iron-oxidizing, free-living diazotroph. This study highlights how environmental sequence data can provide insights for culturing previously uncultured microorganisms.


Longitudinal study of multi-parameter quantitative magnetic resonance imaging in Duchenne muscular dystrophy: hyperresponsiveness of gluteus maximus and detection of subclinical disease progression in functionally stable patients.
To describe the disease progression of Duchenne muscular dystrophy (DMD) in the pelvic and thigh muscles over 1-year using multiple-parameter quantitative magnetic resonance imaging (qMRI), and to determine the most responsive muscle and predict subclinical disease progression in functionally stable patients. Fifty-four DMD patients (mean age 8.9 ± 2.5, range 5-15 years) completed baseline and 1-year follow-up qMRI examinations/biomarkers [3-point Dixon/fat fraction (FF); T1 mapping/T1; T2 mapping/T2]. Meanwhile, clinical assessments [NorthStar ambulatory assessment (NSAA) score] and timed function tests were performed in DMD patients. Twenty-four healthy male controls (range 5-15 years) accomplished baseline qMRI examinations. Group differences were compared using the Wilcoxon test. The standardized response mean (SRM) was taken as the responsiveness to the disease progression index. FF, T1, and T2 in all DMD age subgroups changed significantly over 1-year (P < 0.05). Even in functionally stable patients (NSAA score increased, unchanged, or decreased by 1-point) over 1-year, significant increases in FF and T2 and decreases in T1 were observed in gluteus maximus (GMa), gluteus medius, vastus lateralis, and adductor magnus (P < 0.05). Overall, the SRM of FF, T1, and T2 was all the highest in GMa, which were 1.25, - 0.92, and 0.93, respectively. qMRI biomarkers are responsive to disease progression and can also detect subclinical disease progression in functionally stable DMD patients over 1-year. GMa is the most responsive to disease progression of all the muscles analyzed. Chinese Clinical Trial Registry ( http://www.chictr.org.cn/index.aspx ) ChiCTR1800018340, 09/12/2018, prospectively registered.


Colostomy in children on chronic peritoneal dialysis.
This study aimed to evaluate outcome of children on chronic peritoneal dialysis (PD) with a concurrent colostomy. Patients were identified through the International Pediatric Peritoneal Dialysis Network (IPPN) registry. Matched controls were randomly selected from the registry. Data were collected through the IPPN database and a survey disseminated to all participating sites. Fifteen centers reported 20 children who received chronic PD with a co-existing colostomy. The most common cause of end stage kidney disease was congenital anomalies of the kidney and urinary tract (n = 16, 80%). The main reason for colostomy placement was anorectal malformation (n = 13, 65%). The median age at colostomy creation and PD catheter (PDC) insertion were 0.1 (IQR, 0-2.2) and 2.8 (IQR 0.2-18.8) months, respectively. The colostomies and PDCs were present together for a median 18 (IQR, 4.9-35.8) months. The median age at PDC placement in 46 controls was 3.4 (IQR, 0.2-7.4) months of age. Fourteen patients (70%) developed 39 episodes of peritonitis. The annualized peritonitis rate was significantly higher in the colostomy group (1.13 vs. 0.70 episodes per patient year; p = 0.02). Predominant causative microorganisms were Staphylococcus aureus (15%) and Pseudomonas aeruginosa (13%). There were 12 exit site infection (ESI) episodes reported exclusively in colostomy patients. Seven colostomy children (35%) died during their course of PD, in two cases due to peritonitis. Although feasible in children with a colostomy, chronic PD is associated with an increased risk of peritonitis and mortality. Continued efforts to reduce infection risk for this complex patient population are essential.


Host oxidative stress in piroplasmosis: A review in domestic animals.
Piroplasmida is an order of economically important blood parasites, including Babesia, Theileria, and Cytauxzoon, transmitted to mammals by ticks. Oxidative stress is a state in which the balance between oxidants and antioxidants is disturbed so that antioxidants cannot compensate for the harmful effects of oxidants. Due to the high concentration of oxygen and hemoglobin in red blood cells (RBCs), these are among the first cells exposed to oxidative damage. When RBCs are exposed to oxidative stress, their hemoglobin is oxidized, and lipid peroxidation leads to membrane instability, deformation, hemolysis, and anemia. Oxidative stress has a fundamental role in the pathogenesis of these parasites. In the present review article, we collected studies on the oxidative stress caused by Piroplasmida in domestic animals. What is obtained from the total review of studies conducted on piroplasmosis revealed that in these infections, the host faces oxidative stress, and the resultant oxidative injury plays a fundamental role in their pathogenicity. Further studies are needed to be carried out on the more precise role of oxidative stress, the use of more sensitive diagnostic biomarkers, and the possible therapeutic role of antioxidant agents in piroplasmosis.


Genetic identification of a population of noradrenergic neurons implicated in attenuation of stress-related responses.
Noradrenergic signaling plays a well-established role in promoting the stress response. Here we identify a subpopulation of noradrenergic neurons, defined by developmental expression of Hoxb1, that has a unique role in modulating stress-related behavior. Using an intersectional chemogenetic strategy, in combination with behavioral and physiological analyses, we show that activation of Hoxb1-noradrenergic (Hoxb1-NE) neurons decreases anxiety-like behavior and promotes an active coping strategy in response to acute stressors. In addition, we use cerebral blood volume-weighted functional magnetic resonance imaging to show that chemoactivation of Hoxb1-NE neurons results in reduced activity in stress-related brain regions, including the bed nucleus of the stria terminalis, amygdala, and locus coeruleus. Thus, the actions of Hoxb1-NE neurons are distinct from the well-documented functions of the locus coeruleus in promoting the stress response, demonstrating that the noradrenergic system contains multiple functionally distinct subpopulations.


Relationship between the uptake and cytotoxicity of celiptium in wild type and resistant mutants of the bacterium Streptococcus pneumoniae.
Celiptium, a cationic and amphiphilic drug currently employed in cancer chemotherapy, was found to be accumulated against its concentration gradient by the bacterium Streptococcus pneumoniae. Accumulation was reduced in Celiptium resistant amiA mutants which were also observed to have reduced electric transmembrane potentials delta psi. This suggested a relationship between Celiptium toxicity and accumulation in S. pneumoniae, and indicated a delta psi - driven uptake in a manner reminiscent of that observed for other lipophilic cations such as tetraphenylphosphonium.


Effect of Sex, Use of Pantoprazole and Polymorphisms in SLC22A1, ABCB1, CES1, CYP3A5 and CYP2D6 on the Pharmacokinetics and Safety of Dabigatran.
Dabigatran is a direct oral anticoagulant (DOAC) used for the treatment of several thrombotic conditions. To date, very few pharmacogenetic studies on dabigatran were published. We aimed to investigate the influence of 59 polymorphisms in 15 genes (including CES1, UGT and CYP that encode enzymes and ABCB1 and SLC that encode transporters), concomitant treatment with pantoprazole and demographic characteristics (including sex or race) on dabigatran pharmacokinetics and safety. This was a candidate gene pharmacogenetic study. The study population comprised 107 volunteers enrolled in two dabigatran bioequivalence clinical trials; they were genotyped with a ThermoFisher QuantStudio 12K Flex OpenArray instrument. SPSS software v.21 was used for statistical analysis. Women showed a higher exposure to dabigatran compared to men. The concomitant treatment with pantoprazole was associated with a decreased exposure to the drug. CYP2D6 poor metabolizers (PMs) were related to lower clearance (Cl/F) (p = 0.049) and a tendency was observed towards higher area under the curve (AUC), maximum concentration (Cmax) and to lower volume of distribution (Vd/F) (p < 0.10). SLC22A1 haplotype was related to pharmacokinetic variability (p < 0.05). The remaining genes (including CYP, UGT1A1 and ABCB1) had no effect on dabigatran pharmacokinetics (p > 0.10). Women showed more adverse drug reactions (ADR) compared to men (0.40 ± 0.68 vs 0.15 ± 0.41 ADR per person, p = 0.03) and SLC22A1 mutant haplotype was related to a lower risk of nausea (p = 0.02). Sex, concomitant use of pantoprazole and SLC22A1, CYP2D6 and CYP3A5 polymorphism had an effect on dabigatran pharmacokinetics and safety. Previously published pharmacogenetic predictors, namely CES1 or ABCB1 polymorphisms, had no effect on pharmacokinetics and safety. This study is of interest as it increases the scarce pharmacogenetic information on dabigatran.


A validated LC-MSMS method for the simultaneous quantification of meropenem and vaborbactam in human plasma and renal replacement therapy effluent and its application to a pharmacokinetic study.
A simple method for the simultaneous quantification of meropenem and the recently approved β-lactamase inhibitor, vaborbactam, in human plasma and renal replacement therapy effluent (RRTE) was developed and validated. This antibiotic combination protects a primary β-lactam, meropenem, with a new β-lactamase inhibitor, and expands the limited options for treatment of multidrug-resistant Gram-negative infections. Meropenem, vaborbactam, and the internal standards [2H6]-meropenem and sulbactam in plasma and RRTE were processed using acetonitrile followed by a chromatographic separation on a Poroshell HPH-C18 column with a gradient elution of the mobile phases and monitored using mass spectrometry detection. The calibration range was 0.05 to 100 μg mL-1 for both meropenem and vaborbactam. The intra-day and inter-day precision and accuracy were less than 15% for both meropenem and vaborbactam and the recovery from plasma was 96% for both meropenem and vaborbactam and the recovery from RRTE was 93% and 103% for meropenem and vaborbactam, respectively. This methodology was successfully applied to an ex vivo characterisation study of the effects of renal replacement therapy modalities on the pharmacokinetics of meropenem and vaborbactam (Antimicrob Agents Chemother 62(10), 2018). Graphical abstract.


[Diseases of the upper aerodigestive tract and neck--clinical aspects and challenges for the radiologist].
Based on the anatomy of the neck, some very characteristic inflammatory or tumorous diseases are demonstrated. The question is raised as to how far the radiologist can help the surgeon to estimate the extent e.g. of an abscess or a malignoma, so that the patient can receive the most adequate treatment.


Alteration of non-protein respiratory quotient after hepatocellular carcinoma treatment can be related to des-γ-carboxy prothrombin before treatment.
Transcatheter arterial chemoembolization (TACE) is an effective treatment for hepatocellular carcinoma (HCC) that would occasionally lead to energy malnutrition through therapeutic hypoxic stress. We aimed to clarify the correlation between the energy malnutrition after TACE and low tolerability for hypoxia of non-tumoral liver before TACE. We performed a prospective cohort study involving 100 HCC patients who underwent TACE at Kobe University Hospital. Indirect calorimetry was performed before and 7 days after TACE, and non-protein respiratory quotient (npRQ) as an indicator of the energy malnutrition was measured. Blood biochemical examinations were also performed before TACE. As an indicator of hypoxic marker, des-γ-carboxy prothrombin (DCP) was measured before TACE. The correlation between npRQ ratio (7 days after/before TACE) and DCP (before TACE) was statistically examined. Spearman's correlation coefficient test showed that npRQ ratio (Day 7/Day 0) was significantly related to DCP (Day 0) (p=0.0481, r=-0.2033). On the other hand, npRQ ratio (Day 7/Day 0) was not related to alpha fetoprotein (Day 0) (p=0.6254, r=-0.0494). The npRQ reduction after TACE was related to a high value of DCP before TACE. The energy malnutrition after TACE would originate from low tolerability for hypoxia of non-tumoral liver. The HCC patients with a high value of DCP before TACE would clinically have a high risk of the energy malnutrition after TACE.


XPC deficiency increases risk of hematologic malignancies through mutator phenotype and characteristic mutational signature.
Recent studies demonstrated a dramatically increased risk of leukemia in patients with a rare genetic disorder, Xeroderma Pigmentosum group C (XP-C), characterized by constitutive deficiency of global genome nucleotide excision repair (GG-NER). The genetic mechanisms of non-skin cancers in XP-C patients remain unexplored. In this study, we analyze a unique collection of internal XP-C tumor genomes including 6 leukemias and 2 sarcomas. We observe a specific mutational pattern and an average of 25-fold increase of mutation rates in XP-C versus sporadic leukemia which we presume leads to its elevated incidence and early appearance. We describe a strong mutational asymmetry with respect to transcription and the direction of replication in XP-C tumors suggesting association of mutagenesis with bulky purine DNA lesions of probably endogenous origin. These findings suggest existence of a balance between formation and repair of bulky DNA lesions by GG-NER in human body cells which is disrupted in XP-C patients.


Statistics of N-terminal alignment as a guide for refining prokaryotic gene annotation.
Identification of a correct N-terminus of a protein is an important step in genome annotation. However, we sometimes encounter incorrectly annotated N-termini in genomic databases. We analyzed statistics of surplus or missing N-terminal amino acid residues in tentatively translated coding sequence of cyanobacterial database entries, and found that, on average, about 8-9% of the aligned proteins have a putative incorrect N-terminus, although the percentage was dependent on the database entry. In an attempt to find more plausible N-termini for these proteins, we were able to estimate a better-aligning N-terminus in 90% of the cases. TTG was found as a putative initiation codon in most cases of recessed N-termini. This statistical approach, applicable to any group of prokaryotes, will help identify a plausible translation initiation site for each protein-coding gene in newly sequenced genomes, and also is a method of refining the N-terminus of proteins in already published genomes.


The occurrence and management of fumonisin contamination across the food production and supply chains.
Fumonisins (FUMs) are among the most common mycotoxins in plant-derived food products. FUMs contamination has considerably impacted human and animal health, while causing significant economic losses. Hence, management of FUMs contamination in food production and supply chains is needed. The toxicities of FUMs have been widely investigated. FUMs management has been reported and several available strategies have been developed successfully to mitigate FUMs contamination present in foods. However, currently available management of FUMs contamination from different phases of food chains and the mechanisms of some major strategies are not comprehensively summarized. This review comprehensively characterize the occurrence, impacts, and management of FUMs contamination across food production and supply chains. Pre- and post-harvest strategies to prevent FUMs contamination also are reviewed, with an emphasis on the potential applications and the mechanisms of major mitigation strategies. The presence of modified FUMs products and their potential toxic effects are also considered. Importantly, the potential application of biotechnological approaches and emerging technologies are enunciated. Currently available pre- and post-harvest management of FUMs contamination primarily involves prevention and decontamination. Prevention strategies are mainly based on limiting fungal growth and FUMs biosynthesis. Decontamination strategies are implemented through alkalization, hydrolysis, thermal or chemical transformation, and enzymatic or chemical degradation of FUMs. Concerns have been raised about toxicities of modified FUMs derivatives, which presents challenges for reducing FUMs contamination in foods with conventional methodologies. Integrated prevention and decontamination protocols are recommended to control FUMs contamination across entire value chains in developed countries. In developing countries, several other approaches, including cultivating, introducing Bt maize, simple sorting/cleaning, and dehulling, are suggested. Future studies should focus on biotechnological approaches, emerging technologies, and metagenomic/genomic identification of new degradation enzymes that could allow better opportunities to manage FUMs contamination in the entire food system.


Second-generation antipsychotics: cost-effectiveness, policy options, and political decision making.
The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and other recent research suggest that second-generation antipsychotics other than clozapine may offer few, if any, advantages over first-generation antipsychotics, especially agents of intermediate potency. Thus the newer agents are not likely to generate sufficient benefit to justify their $11.5 billion annual cost. Policy approaches for containing drug costs are available and could improve cost-effectiveness by encouraging that second-generation antipsychotics be prescribed more selectively, such as only when clearly indicated. However, restrictions on either drug availability or physician choice are vigorously opposed by professional and consumer advocacy groups as well as by industry, and excessively restrictive approaches could unintentionally reduce access to beneficial treatments. Interventions that directly reduce second-generation antipsychotic prices would increase access for consumers but are inconsistent with broad opposition to government price regulation in the United States. High expenditures on these medications are thus likely to continue without concomitant gains for public health.


Changes in histone acetylation during oocyte meiotic maturation in the diabetic mouse.
Although there is considerable evidence that diabetes can adversely affect meiosis in mammalian oocytes, acetylation status of oocytes in a diabetic environment remains unclear. The objective was to determine acetylation or deacetylation patterns (based on immunostaining) of H3K9, H3K14, H4K5, H4K8, H4K12, and H4K16 sites at various stages during meiosis in murine oocytes from control and diabetic mice. According to quantitative real time polymerase chain reaction (qPCR), mean ± SEM relative expression of Gcn5 (1.70 ± 0.14 at metaphase [M]I and 1.27 ± 0.01 at MII, respectively), Ep300 (1.74 ± 0.04 at MI and 1.80 ± 0.001 at MII), and Pcaf (2.01 ± 0.03 at MI and 1.41 ± 0.18 at MII) mRNA in oocytes from diabetic mice were higher than those from controls (P < 0.05), whereas there was no difference (P > 0.05) during the germinal vesicle (GV) stage between the two groups (1.23 ± 0.04 for Gcn5, 0.82 ± 0.06 for Ep300, and 0.80 ± 0.07 for Pcaf). Conversely, relative mRNA expression concentrations of Hdac1, Hdac2, Hdac3, Sirt1 and Sirt2 during the germinal vesicle stage were lower in oocytes of diabetic mice (0.24 ± 0.03 for Hdac1, 0.11 ± 0.001 for Hdac2, 0.31 ± 0.03 for Hdac3, 0.28 ± 0.02 for Sirt1, and 0.55 ± 0.02 for Sirt2; P < 0.05). Similarly, the expression concentrations of these genes at the MI stage were lower in oocytes from diabetic mice (0.79 ± 0.12 for Hdac1, 0.72 ± 0.001 for Hdac2, 0.02 ± 0.001 for Sirt1, and 0.84 ± 0.08 for Sirt2; P < 0.05). Their expression concentrations at the MII stage were also lower in oocytes from diabetic mice (0.46 ± 0.03 for Hdac1, 0.93 ± 0.01 for Hdac2, 0.56 ± 0.01 for Hdac3, 0.01 ± 0.002 for Sirt1, and 0.84 ± 0.04 for Sirt2; P < 0.05). At the MI stage, however, there was no difference in the expression of Hdac3 between the two groups of oocytes (0.96 ± 0.03; P > 0.05). Taken together, diabetes altered the intracellular histone modification system, which may have contributed to changes in histone acetylation, and may be involved in the compromised maturation rate of oocytes in diabetic humans.


Image enhancement by acoustic conditioning of ultrasound contrast agents.
A novel contrast imaging technique has been developed for use with microbubble contrast agents. It employs two acoustic fields: there is an excitation field for conditioning microbubbles and an imaging field for detecting microbubbles. The maximum increases (due to microbubble conditioning) in scattered first and second harmonic signals were 14.5 and 16 dB, respectively. This technique is unique for effectively enhancing the blood-to-tissue image contrast.


The Role of School Nurses During the 1918 Pandemic: Lessons That Apply to COVID-19.
The current COVID-19 pandemic has been compared with the Spanish Flu of 1918 that devastated the United States. With so many parallels being drawn, what could be learned from 1918 regarding the role of school nurses? Many of the activities from 1918 are still being done today. School nurses have worked tirelessly to assure the health and safety of students and school. The purpose of this article is to compare the role of school nurses in two pandemics, as well as provide suggestions on how school nurses' important contributions to history are not lost. The recommendations have an added benefit of providing school nurses with healing and building their resilience.


Normal values of liver elasticity measured by real-time tissue elastography (RTE) in healthy infants and children.
To define normal values of liver elasticity measured by real-time tissue elastography (RTE) in healthy infants and children. RTE was performed on 91 children and adolescents by two experienced observers (female, n = 43; male, n = 48) and in two age groups (0-10 years, n = 45; 11-20 years, n = 46). Hepatopathies were excluded clinically by extensive laboratory testing and by ultrasound. RTE provides a histogram from a region of interest (ROI) in the liver representing the degree of stiffness of the liver. The distribution of the colors in the histogram corresponds to organ elasticity. By calculating the mean of stiffness values, a numerical value is expressed in arbitrary units (a.u.) representing the mean elasticity of the liver (MEAN). Additionally, the percentage values of relatively stiffer areas (color coded in blue) in the ROI can be calculated (%AREA). A Mann-Whitney U test was performed for these two parameters according to gender. The reproducibility of these values was determined with an intraclass correlation coefficient (ICC) test on another group of 18 healthy volunteers. The median elasticity was 106 a.u. Gender did not have an influence on the parameters (MEAN: p = 0.052; %AREA: p = 0.051). Age-specific analyses did not yield any significant difference between the two age groups for either of the two analyzed parameters (MEAN: p = 0.059; %AREA: p = 0.058). The ICC test demonstrated a moderate agreement for MEAN (ICC = 0.582) and %AREA (ICC = 0.659). Real-time elastography is a new sonography-based method and may be used as a supportive analysis to assess liver parenchyma elasticity in children, especially when fibrosis is suspected. We measured RTE normal values in children as reference data.


Schistosoma mansoni: cell-mediated immunity evaluated by antigen-induced leukocyte adherence inhibition assay.
Peripheral blood leukocytes (PBL) from schistosomiasis patients fail to adhere to glass in the presence of soluble egg antigens (SEA) or soluble worm adult antigenic preparation (SWAP). These leukocytes are non-reactive with S. mansoni unrelated antigens (C. albicans and bovine albumin). Supernatants obtained from cultures of mononuclear cells of patients with antigens were able to inhibit granulocyte adherence to glass. The inhibition of antigen-induced adherence (LAI assay) was not observed when PBL or supernatants were obtained from normal subjects or from schistosomiasis patients after chemotherapy. These results show that under the conditions tested, leukocytes appear to react directly with SEA or SWAP thus losing their property of adherence to glass.


The early SARS-CoV-2 epidemic in Senegal was driven by the local emergence of B.1.416 and the introduction of B.1.1.420 from Europe.
Molecular surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is growing in west Africa, especially in the Republic of Senegal. Here, we present a molecular epidemiology study of the early waves of SARS-CoV-2 infections in this country based on Bayesian phylogeographic approaches. Whereas the first wave in mid-2020 was characterized by a significant diversification of lineages and predominance of B.1.416, the second wave in late 2020 was composed primarily of B.1.1.420. Our results indicate that B.1.416 originated in Senegal and was exported mainly to Europe. In contrast, B.1.1.420 was introduced from Italy, gained fitness in Senegal, and then spread worldwide. Since both B.1.416 and B.1.1.420 lineages carry several positive selected mutations in the spike and nucleocapsid genes, each of which may explain their local dominance, their mutation profiles should be carefully monitored. As the pandemic continues to evolve, molecular surveillance in all regions of Africa will play a key role in stemming its spread.


Validation and Clinical Application of Interferon-Gamma Release Assay for Diagnosis of Latent Tuberculosis Infection in Children.
India has the highest tuberculosis (TB) burden, accounting for one-fifth of the global incidence and two-third of the cases in Southeast Asia with an estimated 1.9 million new cases every year. Identifying and treating latent TB infection (LTBI) can reduce the risk of development of active disease by up to 90%, thereby decreasing a major burden to the prevalence of the disease, and thus reducing potential sources in future. Early diagnosis of LTBI by tuberculin skin test (TST) and a newer interferon-gamma release assay (IGRA). Seventy-seven clinically asymptomatic household contacts (≤18 years) of confirmed pulmonary TB patients were enrolled to compare the performance of TST and IGRA to diagnose LTBI. At baseline, all participants underwent testing for IGRA and TST. TST showed positivity of 22%, while IGRA demonstrated positivity of 40% in the diagnosis of latent TB. Kappa value at 95% confidence interval was 0.4753, indicates a moderate agreement between the two tests. This indicates that IGRA is a better predictor of latent TB. Maximum positive percentage was in the age group of 16-18 years in both the tests followed by 1-5 years. Early diagnosis of LTBI by tuberculin skin test (TST) and a newer interferon-gamma release assay (IGRA).


Articular manifestations of polymyositis and dermatomyositis.
Nine patients with polymyositis or dermatomyositis associated with arthritis without antinuclear antibodies have been studied. In eight patients a mildly inflammatory nonerosive arthritis occurred coincident with early manifestations or before the appearance of symptomatic muscle disease. Hands, wrists and knees were prominently involved. This arthritis responded to corticosteroids given for the myositis. One patient had erosive arthritis and periarticular calcifications associated with acute inflammation that seemed to diminish with colchicine therapy. Synovial biopsy specimens showed surface fibrin deposition, focal loss of lining cells and mild inflammation--findings similar to those in scleroderma. By electron microscopy tubuloreticular structures were found in vascular endothelium in synovium, as in other tissues in polymyositis. All patients surprisingly had pulmonary manifestations suggesting the possibility that the condition in this group of patients may represent a distinctive subset of polymyositis.


Apolipoprotein C-III isoforms: kinetics and relative implication in lipid metabolism.
Apolipoprotein C-III (apoC-III) production rate (PR) is strongly correlated with plasma triglyceride (TG) levels. ApoC-III exists in three different isoforms, according to the sialylation degree of the protein. We investigated the kinetics and respective role of each apoC-III isoform in modulating intravascular lipid/lipoprotein metabolism. ApoC-III kinetics were measured in a sample of 18 healthy men [mean age (+/-SD) 42.1 +/- 9.5 years, body mass index 29.8 +/- 4.6 kg/m2] using a primed-constant infusion of l-(5,5,5-D3) leucine for 12 h. Mono-sialylated and di-sialylated apoC-III (apo-CIII1 and apoC-III2) exhibited similar PRs (means +/- SD, 1.22 +/- 0.49 mg/kg/day vs. 1.15 +/- 0.59 mg/kg/day, respectively) and similar fractional catabolic rates (FCRs) (0.51 +/- 0.13 pool/day vs. 0.61 +/- 0.24 pool/day, respectively). Nonsialylated apoC-III (apoC-III0) had an 80% lower PR (0.25 +/- 0.12 mg/kg/day) and a 60% lower FCR (0.21 +/- 0.07 pool/day) (P < 0.0001 for comparison with CIII1 and CIII2 isoforms). The PRs of apoC-III1 and apoC-III2 were more strongly correlated with plasma TG levels (r > 0.8, P < 0.0001) than was apoC-III0 PR (r = 0.54, P < 0.05). Finally, the PR of apoC-III2 was strongly correlated with the proportion of LDL <255 A (r = 0.72, P = 0.002). These results suggest that all apoC-III isoforms, especially the predominant CIII1 and CIII2 isoforms, contribute to hypertriglyceridemia and that apoC-III2 may play a significant role in the expression of the small, dense LDL phenotype.


Time-dependent renal pathologies associated with the liver fluke infection, opisthorchiasis felinea.
Fish-borne trematode infections affect the health of more than 18 million people in Russia and Asian countries. Infection of humans and other mammals with the liver fluke Opisthorchis felineus (Rivolta, 1884) is accompanied by gradual development of liver disorders. Although there is indirect evidence that opisthorchiasis may be associated with damage to other organs, direct evidence of the connection between opisthorchiasis felinea and a kidney pathology has not yet been reported. To gain first insights into the possible relation, we investigated time course profiles of blood markers of renal failure as well as renal histological changes during opisthorchiasis from 1 month to 1.5 years postinfection in golden hamsters Mesocricetus auratus. For the first time, we showed that opisthorchiasis felinea leads to the development of glomerulopathy. In particular, O. felineus infection provoked gradual increases in serum creatinine, serum glucose, and urine protein concentrations. Moreover, there was gradual accumulation of renal tubular casts and of the mesangial matrix. Although the mechanisms underlying these renal pathologies remain unclear and require further research, we can conclude that O. felineus infection causes gradual progression of glomerulopathy accompanied by tubulopathy. Thus, overall, these aberrations correlate with the time course of hepatic pathological changes in opisthorchiasis felinea.


Short-term glucose metabolism and gut hormone modulations after Billroth II gastrojejunostomy in nonobese gastric cancer patients with type 2 diabetes mellitus, impaired glucose tolerance and normal glucose tolerance.
Roux-en-Y gastric bypass (RYGB) is effective in controlling blood glucose in obese patients with type 2 diabetes (T2DM). The alterations of gut hormones involving in glucose metabolism may play an important role. Our aim was to explore the short-term effects of Billroth II gastrojejunostomy (a similar type of RYGB) on glucose metabolism and gut hormone modulations in nonobese patients with different levels of blood glucose tolerance. Twenty one nonobese gastric cancer patients with different levels of blood glucose tolerance were submitted to Billroth II gastrojejunostomy. Among them, seven had T2DM, seven with impaired glucose tolerance (IGT) and the other seven had normal glucose tolerance (NGT). Body weight, glucose parameters, responses of plasma glucagon-like peptide-1 (GLP-1), peptide YY (PYY) and gastric inhibitory polypeptide (GIP) to 75 g glucose were measured at baseline and 3 months after surgery. Similar weight losses were observed in all groups. Blood glucose was reduced in T2DM and IGT patients. Fasting and 30-min plasma glucose were increased significantly in NGT. GLP-1 showed insignificant alterations in all groups. PYY was evaluated in T2DM and IGT but remained unchanged in the NGT group. Decreased fasting and AUC GIP were observed in patients with T2DM; however, fasting and 30-min GIP were increased in NGT patients. Billroth II gastrojejunostomy is effective in reducing blood glucose in nonobese patients with T2DM and IGT but could deteriorate early blood glucose in nonobese NGT in a 3-month time period. Variations of glucose and gut hormone changes in the three groups suggest a role of proximal intestine in the pathophysiology of T2DM.


Somatotopic arrangement of sudomotor axon reflex sweating in humans.
Impaired sweating may be one of the first symptoms in neuropathies, and therefore the evaluation of sweating might facilitate their early detection. Sudomotor axon reflexes can be quantified by two different methods: quantitative sudomotor axon reflex testing (QSART) measures the amount of local sweating, whereas staining with the iodine starch reaction assesses the extension of the sudomotor axon reflex area. The aim of our study was to compare both tests at three different sites on the leg: foot, lower leg and thigh. QSART and iodine starch staining after iontophoretic stimulation with acetylcholine were performed on 15 male volunteers (mean age: 25; range 24-27 years) on the left resp. the right leg during a single session. QSART response, measured as area under the curve (AUC), was maximal at the lower leg (911 AUC), smaller at the dorsum of the foot (585 AUC) and even smaller at the thigh (480 AUC). The difference between lower leg and thigh was significant (p < 0.02). The sudomotor axon reflex area was also biggest on the lower leg (39 cm(2)) followed by the foot dorsum (28 cm(2)), and then the thigh (16 cm(2)). The differences between lower leg and thigh as well as between lower leg and foot were significant (p < 0.01, resp. p < 0.04). The size of the sudomotor axon reflex areas and QSART responses were correlated (p < 0.01). QSART and sudomotor axon reflex areas had similar somatotopic arrangements in human skin. The bigger the axon reflex area was the stronger the QSART response was. This indicates that the size of the innervation territories of sudomotor fibres covaries with the amount of local sweat production. The latter is a surrogate for increased sweat gland density or capacity in skin areas of dense sudomotor innervation.


Correction: The burden of dyslipidaemia and factors associated with lipid levels among adults in rural northern Ghana: An AWI-Gen sub-study.
[This corrects the article DOI: 10.1371/journal.pone.0206326.].


Clinical and paraclinical features of small fiber neuropathy in Sjögren's syndrome.
Sjögren's syndrome is a potentially treatable cause of Small Fiber Neuropathy (SFN)-a condition that severely affects patients' quality of life. We therefore aimed to characterize patients with SFN and Sjögren's syndrome to raise awareness of this disease and facilitate its early recognition as an essential step for appropriate treatment. In 97 SFN patients (median age 48 years, 77% female), we studied the clinical features associated with Sjögren's syndrome compared to the idiopathic SFN subtype. According to the current ACR/EULAR classification criteria (Shiboski et al., Ann Rheum Dis 76:9-16, 2017), 24/97 individuals (25%, median age 48.5 years, 75% female) were diagnosed with Sjögren's syndrome. We did not observe any differences in SFN-defining sensory plus symptoms. Furthermore, intraepidermal nerve fiber densities (IENFD) were significantly lower in patients with SFN and Sjögren's syndrome (mean 2.6 ± 1.2/mm) compared to patients with idiopathic SFN (mean 3.2 ± 1.5/mm; p = 0.048). There were no significant group differences when analyzing cerebrospinal fluid (CSF) parameters. We conclude that Sjögren's syndrome-associated SFN is difficult to distinguish from idiopathic forms based on initial clinical symptoms and CSF results. However, lower IENFD values in patients with Sjögren's syndrome-associated SFN might indicate a distinct different pathomechanism in this entity compared to idiopathic SFN.


Calculation of intermolecular interaction strengths in the P beta' phase in lipid bilayers. Implications for theoretical models.
The existence of the P beta' phase in certain lipid bilayers is evidence that molecular interactions between lipids are capable of producing unusual large-scale structures at or near biological conditions. The problem of identifying the specific intermolecular interactions responsible for the structures requires construction of theoretical models capable of clear predictions of the observable consequences of postulated intermolecular interactions. To this end we have carried out a twofold modeling effort aimed at understanding the ripple phase. First, we have performed detailed numerical calculations of potential energies of interaction between pairs and triplets of lipid molecules having different chain tilt angles and relative vertical alignments. The calculations support the notion that chain tilting in the gel phase is a result of successive 3-5-A displacements of neighboring molecules perpendicular to the bilayer plane rather than long-range cooperative chain tilting. Secondly, we have used these results as a guide to formulate a new lattice model for lipid bilayer condensed phases. The new model is less complex than our earlier model and it includes interactions which are, based on the energy calculations, more likely to be responsible for the ripple phase. In a certain limit the model maps onto the chiral clock model, a model of much interest in condensed matter theory. In this limit the model exhibits a chain-tilted ordered phase followed by (as temperature increases) a modulated phase followed by a disordered phase. Within this limit we discuss the properties of the model and compare structures of the modulated phase exhibited by the model with experimental data for the P beta' phase in lipid bilayers.


Emerging industrial clusters of disaster safety industry in Korea.
Disaster-related industries have become essential in strengthening both disaster resilience and national competitiveness. For more efficient disaster management, the Korean government widely integrated the disaster industry with the safety industry in 2013, calling it the "disaster safety industry." This study examines the spatial characteristics of the disaster safety industry and its association with regional industries. In emerging industries such as disaster safety industry, there is a scarcity of information regarding intra-industry transactions, and the industry's scope is often vague, thereby restricting comprehensive analysis. To address this issue, we constructed a quasi-business transaction network that aggregates firm level data to regional level. A correlation analysis using location quotients (LQ) was conducted to determine the relationship with the existing industry. The disaster safety industry network was highly correlated with regional demand. The cluster analysis results showed that four clusters were derived around large cities in the region, which was statistically significant. As a result, these cluster formations were statistically significantly correlated with science- and technology-related industries. Although the disaster safety industry was fostered by the government, we confirmed that technological innovation based on existing industries related to science-based technology can also promote the development of the disaster safety industry.


Transgenerational Abnormalities Induced by Paternal Preconceptual Alcohol Drinking: Findings from Humans and Animal Models.
Alcohol consumption during pregnancy and lactation is a widespread preventable cause of neurodevelopmental impairment in newborns. While the harmful effects of gestational alcohol use have been well documented, only recently, the role of paternal preconceptual alcohol consumption (PPAC) prior to copulating has drawn specific epigenetic considerations. Data from human and animal models have demonstrated that PPAC may affect sperm function, eliciting oxidative stress. In newborns, PPAC may induce changes in behavior, cognitive functions, and emotional responses. Furthermore, PPAC may elicit neurobiological disruptions, visuospatial impairments, hyperactivity disorders, motor skill disruptions, hearing loss, endocrine, and immune alterations, reduced physical growth, placental disruptions, and metabolic alterations. Neurobiological studies on PPAC have also disclosed changes in brain function and structure by disrupting the growth factors pathways. In particular, as shown in animal model studies, PPAC alters brain nerve growth factor (NGF) and brainderived neurotrophic factor (BDNF) synthesis and release. This review shows that the crucial topic of lifelong disabilities induced by PPAC and/or gestational alcohol drinking is quite challenging at the individual, societal, and familial levels. Since a nontoxic drinking behavior before pregnancy (for both men and women), during pregnancy, and lactation cannot be established, the only suggestion for couples planning pregnancies is to completely avoid the consumption of alcoholic beverages.


Cryo-electron tomography of viral infection - from applications to biosafety.
Cellular cryo-electron tomography (cryo-ET) offers 3D snapshots at molecular resolution capturing pivotal steps during viral infection. However, tomogram quality depends on the vitrification level of the sample and its thickness. In addition, mandatory inactivation protocols to assure biosafety when handling highly pathogenic viruses during cryo-ET can compromise sample preservation. Here, we focus on different strategies applied in cryo-ET and discuss their advantages and limitations with reference to severe acute respiratory syndrome coronavirus 2 studies. We highlight the importance of virus-like particle (VLP) and replicon systems to study virus assembly and replication in a cellular context without inactivation protocols. We discuss the application of chemical fixation and different irradiation methods in cryo-ET sample preparation and acquisition workflows.


Assessment of a new device for laser angioplasty.
Experimental work has shown that a transparent laser device delivering pulsed energy to an artery results in a smaller area of surrounding damage than does an opaque device with a continuous wave laser. The combination of a transparent ball-tipped device with a pulsed Nd-YAG laser has been investigated. The system delivers pulses of 100 microseconds at a rate of 10 Hz and average energy of 0.5 J per pulse with an energy loss of 5-10% between the output at the laser rail and the fibre tip. The dose/response was measured and showed that on normal aorta under saline the device produces craters with a depth of 5 microns/J and 1.5 mm radius. There is a 100% increase in dose response with diseased aorta and a 50% increase when exposure is carried out under blood. The effect of a varying angle of incidence upon the arterial wall has been measured. Angulation of the device at 10 degrees from the perpendicular reduces the crater depth to 50%, as compared with a 50% reduction at 60 degrees using a bare fibre. As estimated with a thermal camera in air, the device heats up to a maximum of 50 degrees C during a 50 J exposure, compared to 110 degrees C after 5 J for the sapphire device. Artificial circulation experiments were carried out using diseased femoral vessels occluded by a ligature. The new system recanalised 100% of occlusion in straight vessels, and 40% of occlusions in curved vessels at a radius of 2.5 cm.(ABSTRACT TRUNCATED AT 250 WORDS)


[Clinical and laboratory investigation of four acute myeloid leukemia patients with t(3;3) translocation].
To investigate the clinical and laboratory characteristics of four acute myeloid leukemia with t(3;3) translocation. Bone marrow cell chromosome karyotype analysis were carried out with direct method and short-term culture and R-banding technique. Four AML patients with t(3;3) translocation were identified. They did not obtain complete remission after chemotherapy and the median survival time was 4.5 months. t(3;3) translocation is a rare chromosome abnormality, which has mostly been found in myeloid leukemia and the prognosis of these patients is poor.


Zeralenone and ergosterol contents in corn samples of Transylvania, Romania.
70 corn samples for feed use out of the harvests of the years 2001 and 2002 were collected randomly in Transylvania, Romania and analysed for zearalenone and for ergosterol as fungal mass indicator. High ergosterol contents were found in some samples with a maximum value of 72 mg/kg, zearalenone contents showed values between 4 and 2250 µg/kg in samples positive, indicating a rather high degree of fungal contamination as well as a serious zearalenone contamination.


Ligand binding properties of the human erythropoietin receptor extracellular domain expressed in Escherichia coli.
We developed an assay to directly measure the ligand binding properties of the cloned human erythropoietin receptor (EpoR). The cDNA encoding the extracellular domain of the human EpoR was amplified by polymerase chain reaction and ligated into the prokaryotic expression vector pGEX3X. Synthesis in Escherichia coli was induced and a soluble glutathione S-transferase fusion protein, EREx, was purified by erythropoietin affinity chromatography. Purified EREx was bound to GSH agarose beads and used in a solid phase ligand binding assay. Specific binding of 125I-erythropoietin to EREx beads was demonstrated. A single affinity class (Kd = 1.5 nM) of the binding site was evident on Scatchard analysis. The Kd of this site is quantitatively equivalent to that of the "low" affinity cellular binding site. Kinetic analysis of ligand binding to EREx revealed both the on and off rates to be rapid, with t1/2 of 60 and 40 s, respectively. EREx ligand binding exhibits no obvious metal ion dependence or cross-competition by other hemopoietins. Antibodies to EREx block the binding of erythropoietin to the cellular EpoR. We conclude that the 66-kDa EpoR protein is capable of specific ligand binding and that no covalent modifications or associated molecules are required for this interaction. We speculate that the "high" affinity cellular binding site (Kd less than 0.2 nM) results from the interaction of the EpoR with another molecule, either additional EpoR or associated subunits, that decreases the ligand off rate.


Outcome after Fontan failure and takedown to an intermediate palliative circulation.
Fontan takedown to an intermediate palliative circulation is an important treatment option for patients with acute or subacute failure of a Fontan circulation from a variety of causes. Little is known about the subsequent outcome of these patients or their potential candidacy for a second attempt at Fontan completion. Patients followed up at Children's Hospital Boston who underwent takedown of a Fontan circulation to an intermediate palliative circulation within 1 year of Fontan completion were reviewed. Between 1979 and 2006, 53 patients underwent Fontan takedown at a median age of 2.3 years (range, 0.3 to 36.5 years). Takedown was performed during the Fontan procedure itself in 12 patients (22%), within the first postoperative month in 31(58%), and between 1 month and 1 year in 10 (18%). Overall, 29 patients (55%) survived the early period after takedown, and 19 ultimately underwent successful Fontan completion a median of 4.6 years after takedown; all but one was alive a median of 6.4 years later. Thirteen (68%) of the 19 had treatable abnormalities contributing to Fontan failure. Fontan takedown can provide effective stabilization of the acutely or subacutely failing Fontan circulation, although a substantial number of patients die early despite Fontan takedown. Subjects surviving the perioperative period can often undergo uneventful redo Fontan. A thorough evaluation for treatable abnormalities should be performed in all patients with a failing Fontan circulation and in patients who undergo Fontan takedown.


Removal of carbon constituents from hospital solid waste incinerator fly ash by column flotation.
Hospital solid waste incinerator (HSWI) fly ash contains a large number of carbon constituents including powder activated carbon and unburned carbon, which are the major source of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in fly ash. Therefore, the removal of carbon constituents could reduce PCDD/Fs in fly ash greatly. In this study, the effects of the main flotation parameters on the removal of carbon constituents were investigated, and the characteristics of the final product were evaluated. The results showed that loss on ignition (LOI) of fly ash increased from 11.1% to 31.6% during conditioning process. By optimizing the flotation parameters at slurry concentration 0.05 kg/l, kerosene dosage 12 kg/t, frother dosage 3 kg/t and air flow rate 0.06 m(3)/h, 92.7% of the carbon constituents were removed from the raw fly ash. Under these conditions, the froth product has LOI of 56.35% and calorific values of 12.5 MJ/kg, LOI in the tailings was below 5%, and the total toxic equivalent (TEQ) of PCDD/Fs decreased from 5.61 ng-TEQ/g in the raw fly ash to 1.47 ng-TEQ/g in the tailings. The results show that column flotation is a potential technology for simultaneous separation of carbon constituents and PCDD/Fs from HSWI fly ash.


Calibration and efficiency curve of SANAEM ionization chamber for activity measurements.
A commercially available Fidelis ionization chamber was calibrated and assessed in PTB with activity standard solutions. The long-term stability and linearity of the system was checked. Energy-dependent efficiency curves for photons and beta particles were determined, using an iterative method in Excel™, to enable calibration factors to be calculated for radionuclides which were not used in the calibration. Relative deviations between experimental and calculated radionuclide efficiencies are of the order of 1% for most photon emitters and below 5% for pure beta emitters. The system will enable TAEK-SANAEM to provide traceable activity measurements.


Variability of NT-proBNP and its relationship with inflammatory status in patients with stable essential hypertension: a 2-year follow-up study.
The variability of NT-proBNP levels has been studied in heart failure, yet no data exist on these changes over time in hypertensive patients. Furthermore, studies on the relationship between natriuretic peptides and inflammatory status are limited. 220 clinically and functionally asymptomatic stable patients (age 59 ± 13, 120 male) out of 252 patients with essential hypertension were followed up, and NT-proBNP was measured at baseline, 12 and 24 months. No differences in NT-proBNP were found with respect to the basal stage in the hypertrophic group, but significant changes were found in non-hypertrophic subjects. The reproducibility of NT-proBNP measurements was better in patients with hypertrophy than in the non-hypertrophic group for the three intervals (stage I-basal; stage II-stage I; stage II-basal) with a reference change value of 34%, 35% and 41%, respectively, in the hypertrophic group. A more elevated coefficient of correlation was obtained in the hypertrophic group than in patients without hypertrophy: basal versus stage I (r = 0.79, p < 0.0001 and r = 0.59, p < 0.0001) and stage I versus stage II (r = 0.86, p < 0.0001 and r = 0.56, p < 0.0001). Finally, levels of NT-proBNP significantly correlated with sTNF-R1 (p < 0.0001) and IL-6 (p < 0.01) during follow-up. A multivariate linear regression analysis showed that sTNF-R1 is an independent factor of NT-proBNP. This work shows that there is good stability in NT-proBNP levels in a follow-up study of asymptomatic patients with stable hypertension and left ventricular hypertrophy. As a consequence, assessment of NT-proBNP concentrations may be a useful tool for monitoring the follow-up of hypertensive patients with hypertrophy. Measured variations in peptide levels, exceeding 35% in a 12-month follow-up and 41% in a 24-month follow-up, may indicate an increase in cardiovascular risk, and therefore implies adjustment in the medical treatment. In addition, this study shows a link between neurohormonal and inflammatory activation in these patients.


The pharmacology of curcumin: is it the degradation products?
The natural product curcumin has gained considerable attention in recent years for its multiple pharmacological activities, but more efforts are needed to understand how curcumin can have these pharmacological effects considering its low bioavailability. In addition, it is unclear how curcumin exerts inhibitory effects against numerous enzymes, especially those that cannot accommodate curcumin within recognized binding pockets. By analyzing the similarities between the biological activities of curcumin and its degradation products against diseases such as Alzheimer's disease and cancer, as well as the preferential inhibition of some enzymes by degradation products, it appears that the bioactive degradation products may contribute to the pharmacological effects of curcumin. This possibility should be given full attention when elucidating the pharmacology of this promising natural product for various diseases.


Effect of the β-glucan from Lentinus edodes on colitis-associated colorectal cancer and gut microbiota.
Colorectal cancer is the third most common cancer in the world, and therapies with safety are in great need. In this study, the β-glucan isolated from Lentinus edodes was successfully fractionated into three fractions with different weight-average molecular weight (Mw) by ultrasonic degradation and used for the treatment of colorectal cancer. In our findings, the β-glucan was successfully degraded with the Mw decreased from 2.56 × 106 Da to 1.41 × 106 Da, exhibiting the triple helix structure without conformation disruption. The in vitro results indicate that β-glucan fractions inhibited colon cancer cell proliferation, induced colon cancer cell apoptosis, and reduced inflammation. The in vivo results based on Azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model demonstrate that the lower-molecular weight β-glucan fraction showed stronger anti-inflammatory and anti-colon cancer activities by reconstructing intestinal mucosal barrier, increasing short chain fatty acids (SCFAs) content, regulating metabolism of gut microbiota, and rebuilding the gut microbiota structure with the increased Bacteroides and the decreased Proteobacteria at the phylum level, as well as with the decreased Helicobacter and the increased Muribaculum at the genus level. These findings provide scientific basis for using the β-glucan to regulate gut microbiota as an alternative strategy in the clinical treatment of colon cancer.


Tryptase and Protease-Activated Receptor 2 Expression Levels in Irritable Bowel Syndrome.
Previous studies have revealed that mast cells (MCs) may activate the protease-activated receptors and release of neuropeptides involved in the pathogenesis of irritable bowel syndrome (IBS). The levels of proteaseactivated receptor 2 (PAR-2) and tryptase can contribute to understanding the pathogenesis of IBS. Colonoscopic biopsies were performed of 38 subjects (20 with IBSdiarrhea [IBS-D], eight with IBS-constipation [IBS-C], and 10 healthy volunteers). The mRNA and protein levels of tryptase and PAR-2 were assessed by real-time PCR and Western blot. The levels of vasoactive intestinal peptide (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP) were measured by immunohistochemistry, and MCs were counted by toluidine blue staining. Significant increases in the mRNA expression of tryptase (p<0.05, IBS-D, IBS-C vs control) and PAR-2 (p<0.05, IBS-D, IBS-C vs control) and in the tryptase protein level (p<0.05, IBS-D, IBS-C vs control) were detected in IBS. Elevations of MCs, CGRP, VIP and SP (p<0.05, IBS-D vs control) were observed for IBS-D only. Tryptase levels may upregulate the function of PAR- 2, resulting in the release of neuropeptide and they were correlated with clinical symptoms associated with IBS.


Changes in home range size during growth and maturation of the wood mouse (Apodemus sylvaticus) and the bank vole (Clethrionomys glareolus).
A field study was carried out during winter and spring of 1982/83 to determine changes in home range size with increasing body weight and maturation in the wood mouse (Apodemus sylvaticus) and the bank vole (Clethrionomys glareolus). Individual home range sizes in males increased and in females decreased with increasing body weight. Relating these changes to changed energetic requirements failed. In these species behavioral aspects seem to be a more important determinant of home range size than body weight.


Feasibility and acceptability of peer-delivered HIV self-testing and PrEP for young women in Kampala, Uganda.
Adolescent girls and young women (AGYW) account for 29% of new HIV infections in Uganda despite representing just 10% of the population. Peer support improves AGYW linkage to HIV care and medication adherence. We evaluated the feasibility and acceptability of peer delivered HIV self-tests (HIVST) and oral pre-exposure prophylaxis (PrEP) to young women in Uganda. Between March and September 2021, we conducted a pilot study of 30 randomly selected young women, aged 18-24 years, who had received oral PrEP for at least three months, but had suboptimal adherence as measured by urine tenofovir testing (< 1500 ng/ml). Participants were offered daily oral PrEP and attended clinic visits three and six months after enrollment. Between clinic visits, participants were visited monthly by trained peers who delivered HIVST and PrEP. Feasibility and acceptability of peer-delivered PrEP and HIVST (intervention) were measured by comparing actual versus planned intervention delivery and product use. We conducted two focus groups with young women, and five in-depth interviews with peers and health workers to explore their experiences with intervention delivery. Qualitative data were analyzed using thematic analysis. At baseline, all 30 enrolled young women (median age 20 years) accepted peer-delivered PrEP and HIVST. Peer delivery visit completion was 97% (29/30) and 93% (28/30) at three and six months, respectively. The proportion of participants with detectable tenofovir in urine was 93% (27/29) and 57% (16/28) at months three and six, respectively. Four broad themes emerged from the qualitative data: (1) Positive experiences of peer delivered HIVST and PrEP; (2) The motivating effect of peer support; (3) Perceptions of female controlled HIVST and PrEP; and (4) Multi-level barriers to HIVST and PrEP use. Overall, peer delivery motivated young women to use HIVST and PrEP and encouraged persistence on PrEP by providing non-judgmental client-friendly services and adherence support. Peer delivery of HIVST and oral PrEP was feasible and acceptable to this sample of young women with suboptimal PrEP adherence in Uganda. Future larger controlled studies should evaluate its effectiveness among African AGWY.


The first evidence of antibiofilm action of Proteus mirabilis with tetra-cationic porphyrins containing cisplatin by antimicrobial photodynamic therapy.
Biofilms are responsible for up to 80% of antimicrobial-resistant nosocomial infections. Most of these infections are associated with medical devices such as urinary catheters, and in this context, it is estimated that 90-100% of patients who undergo long-term catheterization develop infections. Proteus mirabilis, the most prevalent microorganism, is responsible for 20-45% of these infections. Thus, this study aimed to evaluate, for the first time, the antimicrobial and antibiofilm effects of cationic porphyrins on P. mirabilis. Neutral porphyrins 3-H2TPyP and 4-H2TpyP and tetra-cationic derivatives 3-cis-PtTPyP and 4-cis-PtTPyP were evaluated in broth microdilution tests to determine the minimum inhibitory and bactericidal concentrations. Time-kill curves, checkerboard test, reactive oxygen species (ROS) scavenger assays, conventional biofilm formation, and biofilm assay with catheters were also performed. The microdilution tests showed greater efficacy against P. mirabilis when 3-cis-PtTPyP was exposed to white-light conditions; this also occurred when the microbial time-kill curve was performed at 0, 2, 6, and 12 h. The radical superoxide species was possibly responsible for photoinactivation in the ROS scavenger assays. In biofilm assays (conventional and catheter), 3-cis-PtTPyP obtained better results when irradiated with a white-light source. In the checkerboard assay, the same compound showed no differences when tested in association with ciprofloxacin hydrochloride. Our findings lead us to conclude that antimicrobial photodynamic therapy and cationic porphyrins obtained positive results and are promising alternatives to treat P. mirabilis biofilms.


N-CPAP in the prevention of recurrent intubations and hospitalizations in a patient with refractory congestive heart failure.
A 61-year-old woman with ischemic cardiomyopathy continued to have recurrent episodes of respiratory failure secondary to acute pulmonary edema requiring ventilatory support on each occasion, despite undergoing surgical revascularization and mitral valve replacement. These episodes of acute respiratory failure were successfully averted by using nocturnal nasal continuous positive airway pressure (N-CPAP). Following N-CPAP, she was able to stay home for 207 consecutive days. Although well-designed, controlled studies are needed to validate this observation, nocturnal N-CPAP is a viable and cost effective option that may be considered in a select number of patients with end-stage cardiopulmonary disease.


Non-T1-weighted 31P chemical shift imaging of the human liver.
A 31P chemical shift imaging (CSI) protocol was developed for human liver studies. It is shown that at the commonly used repetition time (TR) of 1 s T1-weighting reduces the integrated intensities of liver phosphate metabolite signals by 18 +/- 15% (inorganic phosphate, Pi) to 46 +/- 10% (phosphodiester, PDE), that is for an RF pulse angle of 60 degrees (weighted average) in liver. The loss in signal-to-noise ratio (S/N) at TR = 20 s, sufficient to eliminate spectral distortions caused by saturation, compared with TR = 1 s (47-65%) can be overcome by using one-dimensional (1D)-phase encoding with a small number of phase-encode steps. The liver spectra obtained by 1D-CSI with 4-step phase-encoding (spatial resolution 10 cm) have the highest S/N and, after multiplication of the PDE signal by a factor of 1.4, closely reflect the liver metabolite levels. It is concluded that clinical 31P MR studies of liver function can be performed without T1-weighting and that the current practice to compromise the MRS quantification of lever metabolites with uncertainties caused by (differential changes in) T1-weighting is not warranted.


Aged-look vat dyed cotton with anti-bacterial/anti-fungal properties by treatment with nano clay and enzymes.
In this research, nanotechnology as a route to functional finishing of textiles was used along with bio-finishing to enhance the cotton fabrics performance. For this purpose, quaternary modified montmorillonite and common enzymes such as cellulase, laccase and their mixture were applied on vat dyed cotton fabric. Characteristic analysis of the treated samples and the dispersed nano clays in the effluent of the treatment was performed by various analyzing methods. The nano/bio-finishing is believed to impart antibacterial and antifungal activities with simultaneously higher lightness, advanced softness and handle properties into cotton fabrics. Moreover, cotton fabrics were proved to have no adverse effects (low toxicity) on human dermal fibroblasts. Findings suggest the potential of the proposed method in reducing the risk of microorganism for textile applications and imparting better handle and appearance properties.


Bupropion Hydrochloride.
Bupropion hydrochloride is a norepinephrine-dopamine disinhibitor (NDDI) approved for the treatment of depression and smoking cessation. Bupropion is a trimethylated monocyclic phenylaminoketone second-generation antidepressant, which differs structurally from most antidepressants, and resides in a novel mechanistic class that has no direct action on the serotonin system. Comprehensive chemical, physical, and spectroscopic profiles are presented. This analytical profile provides an extensive spectroscopic investigation utilizing mass spectrometry, one- and two-dimensional NMR, solid-state NMR, IR, NIR, Raman, UV, and X-ray diffraction. The profile also includes significant wet chemistry studies for pH, solubility, solution, and plasma stability. Both HPLC and UPLC methodology are presented for bupropion and its related impurities or major metabolites. The profile concludes with an overview of biological properties that includes toxicity, drug metabolism, and pharmacokinetics.


Left internal mammary artery injury requiring resuscitative thoracotomy: a case presentation and review of the literature.
Background. Penetrating injuries to the chest and in particular to the heart that results in pericardial tamponade and cardiac arrest requires immediate resuscitative thoracotomy as the only lifesaving technique and should be performed without delay. Objective. To describe an external cardiac tamponade caused by massive tension hemothorax from penetrating injury of the left internal mammary artery (LIMA). Method. A case presentation treated at the Level I trauma center at Hamad General Hospital, in Doha, Qatar and review of the literature on LIMA injuries reported cases. Results. LIMA injury as a cause of hemothorax is not uncommon, but to our knowledge our case is the first massive tension hemothorax with witnessed cardiac arrest reported in the literature requiring emergency thoracotomy, performed in trauma room, with full recovery. Conclusion. Injury to the LIMA with massive tension hemothorax requires immediate resuscitative thoracotomy.


Identification of active or inactive agonists of tumor suppressor protein based on Tox21 library.
Exposure of cells to xenobiotic human-made products can lead to genotoxicity and cause DNA damage. It is an urgent need to quickly identify the chemicals that cause DNA damage, and their toxicity should be predicted. In this study, recursive partitioning (RP), binary logistic regression, and one machine learning approach, namely, random forest (RF) classifier, were used to predict the active and inactive compounds of a total 5036 data based on the assay conducted by a β-lactamase reporter gene under control of the p53 response element (p53RE) from Tox21 library. Results show that the binary logistic regression model with a threshold of 0.5 has a high accuracy rate (83%) to distinguish active and inactive compounds. The RF classifier method has satisfactory results, with an accuracy rate (84.38%) approximately higher than that of binary logistic regression. The models established can identify compounds that induce DNA damage and activate p53, and provide a scientific basis for the risk assessment of organic chemicals in the environment.


The association of the decline in glomerular filtration rate with aggressive endometrial cancers.
Most site-specific cancer incidence is increased with the decrease of glomerular filtration rate (GFR). We analyzed endometrial cancers depending on different type, staging, and histology grades. We hypothesized that patients with lower GFR levels have an increased risk for higher staging and histology grades of endometrial cancers. Patients were divided into two subgroups regarding GFR; the first group with GFR < 60 ml/min and the second group with GFR > 60 ml/min and regarding different histology grades and cancer stages. Cancers were also divided by stages (1-4). Patients were followed up during 1 year through regular controls in the outpatient clinic and during that time cancer recurrence was recorded. GFR was the strongest predictor for higher cancer histology grade and higher cancer staging. Patients with reduced GFR had OR for higher histology grade and higher staging of 1.06 and 1.06. Traditional risk factors for endometrial cancer development were not associated with higher histology grade or higher cancer staging. Higher staging and histology grades in patients with endometrial cancers are associated with reduced GFR. Patients with mild-to-moderate CKD had significantly higher number of cancers with higher histology grades and higher stages than patients with mild or normal GFR category. Decline in GFR was independently associated with more aggressive cancers without other well-known risk factors for endometrial cancer development like age, menopause, diabetes, and obesity.