Depression, Anxiety, and Alcohol Use Among LGBTQ+ People During the COVID-19 Pandemic.
Objectives. To describe disparities in depression, anxiety, and problem drinking by sexual orientation, sexual behavior, and gender identity during the COVID-19 pandemic. Methods. Data were collected May 21 to July 15, 2020, from 3245 adults living in 5 major US metropolitan areas (Atlanta, Georgia; Chicago, Illinois; New Orleans, Louisiana; New York, New York; and Los Angeles, California). Participants were characterized as cisgender straight or LGBTQ+ (i.e., lesbian, gay, bisexual, and transgender people, and men who have sex with men, and women who have sex with women not identifying as lesbian, gay, bisexual, or transgender). Results. Cisgender straight participants had the lowest levels of depression, anxiety, and problem drinking compared with all other sexual orientation, sexual behavior, and gender identity groups, and, in general, LGBTQ+ participants were more likely to report that these health problems were "more than usual" during the COVID-19 pandemic. Conclusions. LGBTQ+ communities experienced worse mental health and problem drinking than their cisgender straight counterparts during the COVID-19 pandemic. Future research should assess the impact of the pandemic on health inequities. Policymakers should consider resources to support LGBTQ+ mental health and substance use prevention in COVID-19 recovery efforts.


Efficacy of tramadol as a preincisional infiltration anesthetic in children undergoing inguinal hernia repair: a prospective randomized study.
Preincisional local anesthetic infiltration at the surgical site is a therapeutic option for postoperative pain relief for pediatric inguinal hernia. Additionally, tramadol has been used as an analgesic for postoperative pain in children. Recently, the local anesthetic effects of tramadol have been reported. The aim of this study was to determine both the systemic analgesic and the local anesthetic effects of tramadol and to determine how it differs from bupivacaine when administered preincisionally. Fifty-two healthy children, aged 2-7 years, who were scheduled for elective herniorrhaphy were randomly allocated to receive either preincisional infiltration at the surgical site with 2 mg/kg tramadol (Group T, n=26) or 0.25 mL/kg 0.5% bupivacaine (Group B, n=26). At the time of anesthetic administration, perioperative hemodynamic parameters were recorded. The pain assessments were performed 10 minutes after the end of anesthesia and during the first 6-hour period, using pain scores. The time of first dose of analgesia and need for additional analgesia were recorded. Between T and B groups, the anesthesia time, perioperative hemodynamic changes, and pain scores were not statistically different. However, in group B, the postoperative analgesic requirement was higher than in group T. Tramadol shows equal analgesic effect to bupivacaine and decreases additional analgesic requirement, when used for preincisional infiltration anesthesia in children undergoing inguinal herniorrhaphy.


Structural properties of azobenzene self-assembled monolayers by atomistic simulations.
Azobenzene self-assembled monolayers (SAMs) are examples of optomechanical nanostructures capable of producing mechanical work through the well-known azobenzene photoisomerization process. Experimental studies have provided information on their structural properties, but an atomistic description of the SAMs in both the cis and trans forms is still lacking. In this work, a computational investigation of the SAM structures is conducted by classical molecular dynamics with a dedicated force. Experimental data on the SAM unit cell is used to set up SAM models of different molecular densities. The optimal structures are identified through the comparison with structural data from X-ray photoelectron and near-edge X-ray absorption fine structure spectroscopies. The resulting SAM atomistic models are validated by comparing simulated and experimental scanning tunneling microscopy images.


DNA Fragmentation in Viable and Non-Viable Spermatozoa Discriminates Fertile and Subfertile Subjects with Similar Accuracy.
Sperm DNA fragmentation (sDF) negatively affects reproduction and is traditionally detected in total sperm population including viable and non-viable spermatozoa. Here, we aimed at exploring the ability of DNA fragmentation to discriminate fertile and subfertile men when detected in viable (viable sDF), non-viable (non-viable sDF), and total spermatozoa (total sDF). We revealed sDF in 91 male partners of infertile couples and 71 fertile men (max 1 year from natural conception) with LiveTUNEL coupled to flow cytometry, able to reveal simultaneously DNA fragmentation and cell viability. We found that the three sDF parameters discriminated fertile and subfertile men with similar accuracy and independently from age and basal semen parameters: AUCs (area under the curves) (95% CI) were: 0.696 (0.615-0.776), p < 0.001 for total sDF; 0.718 (0.640-0.797), p < 0.001 for viable sDF; 0.760 (0.685-0.835), p < 0.001 for non-viable sDF. We also found that total and non-viable but not viable sDF significantly correlated to age and semen quality. In conclusion, the three sDF parameters similarly discriminated fertile and subfertile men. Viable spermatozoa with DNA fragmentation are likely cells able to fertilize the oocyte but failing to properly support subsequent embryo development. Non-viable sDF could be a sign of a subtler damage extended beyond the non-viable cells.


Correlation between Serum Leptin Levels, Body Mass Index and Obesity in Omanis.
To ascertain the relationship between serum leptin levels and related variables (weight, Body Mass Index (BMI) and fat percentage) in a group of Omani obese and non-obese healthy subjects. Leptin levels were assessed in serum samples from 35 obese Omanis and 20 non-obese healthy subjects. There was a significant difference (p< 0.001) in serum leptin between the obese group (34.78 + 13.96 ng/ml) and the control non-obese subjects (10.6 ± 4.2 ng/ml). Leptin levels were higher in females compared to males. There was a significantly positive correlation between leptin levels in obese subjects with weight (p=0.002), body fat percentage (p=0.0001) and BMI (p=0.001). We concluded that serum leptin levels are higher in the Omani obese group and correlate positively with body fatness and obesity.


T cryptantigen activation is associated with advanced necrotizing enterocolitis.
Thomsen-Friedenreich cryptantigen activation (TCA) exposes neonates with necrotizing enterocolitis NEC to the risk of hemolysis after transfusion of blood products. The authors aimed to determine the prevalence of TCA in neonates with NEC and to correlate TCA with severity of disease and outcome. One hundred four neonates with NEC were tested for TCA on admission. Patients with TCA requiring transfusion were given packed red cells, low-titer anti-T fresh frozen plasma, and washed platelets to avoid hemolysis. Twenty-three infants had TCA, and 96% of these had stage III disease. The incidence of TCA was significantly higher in infants with stage III disease compared with those with stage II (30% v 4%; P <.01). A total of 91% of infants with TCA required laparotomy compared with 81% of those with no activation. At laparotomy, widespread disease was more common in the TCA group (71% v 55%). TCA did not significantly increase mortality rate (TCA, 39% v no TCA, 28%); this may reflect the transfusion policy of our unit. Twenty-two percent of neonates with NEC referred to our unit had TCA. There is an association between TCA and advanced NEC. Screening of neonates with advanced NEC for TCA is advised to identify those at risk of hematologic complications.


The impact of diagnostic wait time on the survival of patients with diffuse large B-cell lymphoma: effect modification by the International Prognostic Index.
Despite the importance of a prompt diagnosis to improve cancer patients' survival, little has been reported on diagnostic delay in diffuse large B-cell lymphoma (DLBCL). A single-centre, retrospective study was conducted to examine the association between diagnostic wait time (DWT), the interval from the initial hospital visit to diagnosis, and survival in patients with DLBCL. A total of 193 patients were enrolled from 2007 to 2017 in our institution. A covariate-adjusted Cox proportional hazards model with restricted cubic spline was used to evaluate the impact of DWT on survival, with a subgroup analysis according to the International Prognostic Index (IPI). DWT was not associated with survival in the entire DLBCL population, but the impact of DWT on survival differed between IPI < 3 and ≥ 3; prolongation of DWT steadily exacerbated the prognosis in patients with IPI ≥ 3, whereas there was a patient population with IPI < 3 who had a high mortality rate despite rather early diagnosis. The opposite trend in the effect of DWT on survival between patients with IPI < 3 and ≥ 3 offset survival in all DLBCL patients. DWT had no observable impact on outcomes in the entire DLBCL population, but longer DWT worsened the prognosis, particularly in patients with IPI ≥ 3.


Prognostic Factors and Survival in Non-Small Cell Lung Cancer Patients Treated with Chemoradiotherapy.
According to the literature, performance status, stage-tumor dimension and nodal status, weight loss, were the most important prognostic factors for survival in patients with locally advanced non-small cell lung cancer. To evaluate the treatment results and the prognostic variables in our patients treated with sequential and concurrent chemoradiotherapy. In the study 85 patients were randomly assigned to one of the two treatment arms. In the sequential arm, 45 patients had previously received sequential chemotherapy with 4 cycles of and etoposide followed by conformal radiotherapy (RT). In the second concurrent group, 40 patients received concomitant chemotherapy of cisplatine and etoposide and conformal RT, followed by two cycles of consolidation chemotherapy of carboplatine and etoposide. We described all phases of the conformal three dimensional (3-D) RT. From October 2005 to March 2008, 93 patients were enrolled. Eight patients were not eligible, seven had stage IV and one patient had pleural effusion. They were all initially considered to have stage IIIB disease. The median survival was 13 months for the patients in the sequential arm and 19 months for those in the concurrent treatment arm. The differences were statistically significant (log-rank test p=0.0039). The disease-free survival was 9 months in the sequential arm and 16 months in the concurrent treatment group. The differences were statistically significant (log-rank test p=0.0023). We found that the following prognostic factors significantly influenced the survival in lung cancer patients treated with conservative method: - age, p<0.05; - performant status, p<0.001; - weight loss, p<0.001; tumor dimension, p<0.05; and - nodal involvement, p<0.05. In our study, the dose-limiting toxicity, esophagitis was reduced by performing conformal radiotherapy. Conformal thoracic radiotherapy and new radiotherapy technics, such as respiratory gated radiotherapy, allow dose escalating and may probably improve survival and local control in lung cancer patients.


Applying machine learning to detect early stages of cardiac remodelling and dysfunction.
Both left ventricular (LV) diastolic dysfunction (LVDD) and hypertrophy (LVH) as assessed by echocardiography are independent prognostic markers of future cardiovascular events in the community. However, selective screening strategies to identify individuals at risk who would benefit most from cardiac phenotyping are lacking. We, therefore, assessed the utility of several machine learning (ML) classifiers built on routinely measured clinical, biochemical, and electrocardiographic features for detecting subclinical LV abnormalities. We included 1407 participants (mean age, 51 years, 51% women) randomly recruited from the general population. We used echocardiographic parameters reflecting LV diastolic function and structure to define LV abnormalities (LVDD, n = 252; LVH, n = 272). Next, four supervised ML algorithms (XGBoost, AdaBoost, Random Forest (RF), Support Vector Machines, and Logistic regression) were used to build classifiers based on clinical data (67 features) to categorize LVDD and LVH. We applied a nested 10-fold cross-validation set-up. XGBoost and RF classifiers exhibited a high area under the receiver operating characteristic curve with values between 86.2% and 88.1% for predicting LVDD and between 77.7% and 78.5% for predicting LVH. Age, body mass index, different components of blood pressure, history of hypertension, antihypertensive treatment, and various electrocardiographic variables were the top selected features for predicting LVDD and LVH. XGBoost and RF classifiers combining routinely measured clinical, laboratory, and electrocardiographic data predicted LVDD and LVH with high accuracy. These ML classifiers might be useful to pre-select individuals in whom further echocardiographic examination, monitoring, and preventive measures are warranted.


Guinea Pig Oxygen-Sensing and Carotid Body Functional Properties.
Mammals have developed different mechanisms to maintain oxygen supply to cells in response to hypoxia. One of those mechanisms, the carotid body (CB) chemoreceptors, is able to detect physiological hypoxia and generate homeostatic reflex responses, mainly ventilatory and cardiovascular. It has been reported that guinea pigs, originally from the Andes, have a reduced ventilatory response to hypoxia compared to other mammals, implying that CB are not completely functional, which has been related to genetically/epigenetically determined poor hypoxia-driven CB reflex. This study was performed to check the guinea pig CB response to hypoxia compared to the well-known rat hypoxic response. These experiments have explored ventilatory parameters breathing different gases mixtures, cardiovascular responses to acute hypoxia, in vitro CB response to hypoxia and other stimuli and isolated guinea pig chemoreceptor cells properties. Our findings show that guinea pigs are hypotensive and have lower arterial pO2 than rats, probably related to a low sympathetic tone and high hemoglobin affinity. Those characteristics could represent a higher tolerance to hypoxic environment than other rodents. We also find that although CB are hypo-functional not showing chronic hypoxia sensitization, a small percentage of isolated carotid body chemoreceptor cells contain tyrosine hydroxylase enzyme and voltage-dependent K+ currents and therefore can be depolarized. However hypoxia does not modify intracellular Ca2+ levels or catecholamine secretion. Guinea pigs are able to hyperventilate only in response to intense acute hypoxic stimulus, but hypercapnic response is similar to rats. Whether other brain areas are also activated by hypoxia in guinea pigs remains to be studied.


Factors related to medication non-adherence for patients with hypertension in Taiwan.
To characterise a Taiwanese population and to examine the prevalence of antihypertensive medication non-adherence and how the cultural/clinical factors were associated with non-adherence in Taiwan. Antihypertensive medication non-adherence is a significant clinical issue in the United States. However, little is known about hypertension (HTN) control and cultural/clinical factors related to non-adherence in Taiwan. A convenience sample survey design was used. Data were gathered from a convenience sample of 200 subjects recruited from a large teaching hospital. Medication non-adherence and cultural/clinical factors were recorded using various self-administered questionnaires, and blood pressure was taken twice for each participant. The mean age of the participants was 60.4 (SD 11.5 years) including 62% men. Two-thirds had less than a high school education (64.5%), and the majority of them were married (86·0%) and lived with family or close friends (93.5%). The average length of HTN diagnosis was 8.6 years (SD 9.0 years). Medication non-adherence rate was 47·5%, and uncontrolled HTN rate was 49.0%. Some participants (17.0%) used Chinese herbs for treating their disease (e.g. cough) and promoting health in addition to their regular antihypertensive medications. Two factors were found to be statistically significant for predicting medication non-adherence: Lower Perceived Susceptibility to Specific Diseases [OR = 1.15 (95%CI, 1.01-1.31)] and Longer Length of HTN Diagnosis [OR = 1.06 (95%CI, 1.01-1.12)]. Taiwanese at risk of non-adherence included those who perceived lower susceptibility to specific diseases and had been diagnosed with HTN for a longer time. Those using herbs need to be studied for an impact of herbs on their adherence behaviour. These findings can help guide the development of culturally sensitive and clinically appropriate nursing interventions for HTN management in Taiwan.


Differential expression of Toll-like receptors in chronic hyperplastic candidosis.
The first step in the host defense against oral candidosis is the recognition of Candida albicans through a set of germ-encoded pathogen recognition receptors, e.g. Toll-like receptors (TLRs). In man, 10 types of such receptors have been identified so far, of which only TLR2, TLR4, and TLR6 have been linked to mediating candidal ligands, e.g. zymosan. Biopsies from patients with chronic hyperplastic candidosis (n = 5), leukoplakia (n = 5), and healthy mucosa (n = 5) were immunohistochemically stained with antibodies to the TLRs (TLR1 to TLR9) to distinguish and compare the staining patterns of the epithelial layer in the three categories of tissues. On analysis, the epithelium of all tissues was divided into three layers: basal, middle, and superficial. Two of the five chronic hyperplastic candidosis sections showed high numbers of hyphae compared to yeasts, which paralleled a decrease in the expression of TLR2 and an increase in the staining intensity of TLR4. Leukoplakia and healthy tissue sections demonstrated stronger immunostaining of TLRs, except TLR9 which showed weaker staining in some sections of the former, and in the basal layers of some sections of the latter. This study supports the concept of negative regulation of TLRs that are either ligand-bound (e.g. in chronic hyperplastic candidosis), or not stimulated (in healthy tissue). It also augments the opinion that C. albicans, through its hyphae rather than blastospore, may utilize TLRs, i.e. TLR2, to evade the immune system of the host. Leukoplakia seems to be more immunologically alert, which reduces the chances of worsening the already-diseased tissue.


Adhesion onto and invasion into mammalian cells by mycoplasma penetrans: a newly isolated mycoplasma from patients with AIDS.
The newly identified mycoplasma, Mycoplasma pentrans shows remarkable pathobiologic properties: it adheres to cell surfaces, deeply penetrates into the cell, strongly hemadsorbs human red blood cells, and cytadsorbs human CD4+ lymphocytes and monocytes. These in vitro biologic activities of mycoplasmas have been previously shown to be associated with pathogenic virulence in vivo. Both adhesion and invasion clearly involve the organism's unique tip-like structure. Invading mycoplasmas often have their tip-like structure deeply buried in the cytoplasm of infected mammalian cells. Extensive invasion of the mycoplasma into the cytoplasm may kill the cells. The same pathobiologic processes of adhesion and invasion using the specialized tip-like structure are found on the epithelium in the patient's urogenital tract infected by M. penetrans. Both in vitro and in vivo findings suggest a possible pathogenic role of this newly discovered human mycoplasma and call for careful evaluation of its role in human diseases.


Bone marrow and spleen morphology following haemolytic anaemia in adult laboratory rats of various age groups.
We induced toxic-haemolytic events in 8, 11 and 29-w-old rats after single dose of nitrobenzene, 3-chloro-4-benzyloxyphenacetic acid and phenacetin administered orally. Large individual variability of haematological changes in rat marrow and spleen morphology was found. The use of groups of laboratory rats of different age significantly modified reactions in characteristics investigated but common simple age-related changes were not clearly demonstrated.


Cross-sectional associations between adolescents' physical literacy, sport and exercise participation, and wellbeing.
Adolescence is a significant period in one's development of positive emotional and social wellbeing. Physical literacy (PL) is considered a determinant of physical health and wellbeing and is thought to be the foundation for an individual's engagement in physical activities. Yet, limited evidence exists on PL's association with adolescents' health and physical activity behavior. This study aims to (1) explore the associations between Danish adolescents' PL and their emotional and social wellbeing, (2) examine whether these associations are mediated by sport and exercise participation (SEP), and (3) consider if the associations differ across sex. Cross-sectional data from a national population survey were collected in 2020. The sample consisted of 1,518 Danish adolescents aged 13-15 years. PL was assessed with the validated MyPL questionnaire. The weekly time engaged in sports and exercise was self-reported. Self-esteem, life satisfaction, body satisfaction, and loneliness were measured with items from the standardized HBSC questionnaire, and a wellbeing composite score was calculated from these four measures. We constructed structural equation models with PL and sports and exercise participation as independent variables and the five aspects of wellbeing as dependent variables. Positive associations were observed between PL and SEP (β = 0.33, p < 0.001) and between PL and the five aspects of wellbeing with β-values between 0.19 and 0.30 (p < 0.001). These associations were greater among girls. The association between PL and four of the five wellbeing outcomes were partly mediated by SEP with indirect effects (β) between 0.03 and 0.05. Results from this study support the hypotheses that PL is important for children and adolescents' wellbeing and physical activity behavior.


Coleus vettiveroides ethanolic root extract induces cytotoxicity by intrinsic apoptosis in HepG2 cells.
Hepatocellular carcinoma (HCC) contributes to more than 80% of all primary cancers globally and ranks fourth in cancer-related deaths, due to the lack of an effective, definite therapeutic drug. Coleus vettiveroides (CV) has been used in Indian traditional medicine to treat diabetes, liver ailments, skin diseases, leukoderma, and leprosy. This study investigates the anticancer effect of CV ethanolic root extract in HepG2 cells. HepG2 cells were treated with CV extract, and its cytotoxicity was analyzed by MTT assay. AO/EB staining, propidium iodide staining, DCFH-DA assay, phalloidine staining, flow cytometry, and qPCR studies were performed for ROS expression, apoptosis and cell cycle analysis. The phytochemical analysis confirmed the presence of quercetin and galangin in CV root extract. The results showed that CV inhibited the proliferation of HepG2 cells, with altered cellular and nuclear morphology. CV was also found to increase intracellular ROS levels and oxidative stress markers in HepG2 cells. CV significantly altered the actin microfilament distribution in HepG2 cells and caused cell cycle arrest at the sub G0 -G1 phase. CV also induced mitochondria-mediated apoptosis, as evidenced by increased expression of p53, Bax, cytochrome C, Apaf-1, PARP, caspase-3 and caspase-9, and downregulated Bcl-2 expression. Therefore, CV exerts its anticancer effect by inducing mitochondrial dysfunction, oxidative stress, cytoskeletal disorganization, cell cycle arrest, and mitochondria-mediated apoptosis, and it could be a potent therapeutic option for HCC.


A 1.1-Mb transcript map of the hereditary hemochromatosis locus.
In the process of positionally cloning a candidate gene responsible for hereditary hemochromatosis (HH), we constructed a 1.1-Mb transcript map of the region of human chromosome 6p that lies 4.5 Mb telomeric to HLA-A. A combination of three gene-finding techniques, direct cDNA selection, exon trapping, and sample sequencing, were used initially for a saturation screening of the 1.1-Mb region for expressed sequence fragments. As genetic analysis further narrowed the HH candidate locus, we sequenced completely 0.25 Mb of genomic DNA as a final measure to identify all genes. Besides the novel MHC class 1-like HH candidate gene HLA-H, we identified a family of five butyrophilin-related sequences, two genes with structural similarity to a type 1 sodium phosphate transporter, 12 novel histone genes, and a gene we named RoRet based on its strong similarity to the 52-kD Ro/SSA lupus and Sjogren's syndrome auto-antigen and the RET finger protein. Several members of the butyrophilin family and the RoRet gene share an exon of common evolutionary origin called B30-2. The B30-2 exon was originally isolated from the HLA class 1 region, yet has apparently "shuffled" into several genes along the chromosome telomeric to the MHC. The conservation of the B30-2 exon in several novel genes and the previously described amino acid homology of HLA-H to MHC class 1 molecules provide further support that this gene-rich region of 6p21.3 is related to the MHC. Finally, we performed an analysis of the four approaches for gene finding and conclude that direct selection provides the most effective probes for cDNA screening, and that as much as 30% of ESTs in this 1.1-Mb region may be derived from noncoding genomic DNA.


Simulated astigmatism impairs academic-related performance in children.
Astigmatism is an important refractive condition in children. However, the functional impact of uncorrected astigmatism in this population is not well established, particularly with regard to academic performance. This study investigated the impact of simulated bilateral astigmatism on academic-related tasks before and after sustained near work in children. Twenty visually normal children (mean age: 10.8 ± 0.7 years; six males and 14 females) completed a range of standardised academic-related tests with and without 1.50 D of simulated bilateral astigmatism (with both academic-related tests and the visual condition administered in a randomised order). The simulated astigmatism was induced using a positive cylindrical lens while maintaining a plano spherical equivalent. Performance was assessed before and after 20 min of sustained near work, during two separate testing sessions. Academic-related measures included a standardised reading test (the Neale Analysis of Reading Ability), visual information processing tests (Coding and Symbol Search subtests from the Wechsler Intelligence Scale for Children) and a reading-related eye movement test (the Developmental Eye Movement test). Each participant was systematically assigned either with-the-rule (WTR, axis 180°) or against-the-rule (ATR, axis 90°) simulated astigmatism to evaluate the influence of axis orientation on any decrements in performance. Reading, visual information processing and reading-related eye movement performance were all significantly impaired by both simulated bilateral astigmatism (p < 0.001) and sustained near work (p < 0.001), however, there was no significant interaction between these factors (p > 0.05). Simulated astigmatism led to a reduction of between 5% and 12% in performance across the academic-related outcome measures, but there was no significant effect of the axis (WTR or ATR) of astigmatism (p > 0.05). Simulated bilateral astigmatism impaired children's performance on a range of academic-related outcome measures irrespective of the orientation of the astigmatism. These findings have implications for the clinical management of non-amblyogenic levels of astigmatism in relation to academic performance in children. Correction of low to moderate levels of astigmatism may improve the functional performance of children in the classroom.


What Kind of Doctor Do You Want to Be? Geriatric Medicine Podcast as a Career Planning Resource.
For optimal direction in career paths and postgraduate training, students can benefit from information to guide them through options. Using geriatric medicine as a template, the goal was to develop a multimedia podcast resource that can give a clearer picture of what a specialty entails. The project included a survey of existing resources and needs assessment of medical students at the University of Ottawa, Canada. This survey assessed students' knowledge of geriatrics and interest in the field and explored what they foresee as being important to be informed on when considering application to programs. Based on this, interview questions and content were developed for a podcast which was then evaluated. Interviews were conducted with physicians and residents nationwide. Relevant resources and links were added to the podcast. Evaluation demonstrated improved student understanding and interest in geriatric medicine as a career. Point-by-point format for a template on how to develop similar podcasts was developed to assist other specialties looking to develop similar information. As no such framework currently exists, results of this project can serve as a template for other postgraduate programs in developing a multimedia resource for informing prospective trainees.


Three-dimensional imaging in aortic disease by lighthouse transesophageal echocardiography using intravascular ultrasound catheters. Comparison to three-dimensional transesophageal echocardiography and three-dimensional intra-aortic ultrasound imaging.
Two-dimensional (2D) transesophageal echocardiography (TEE) and 2D intravascular ultrasound (IVUS) imaging face their greatest limitation in visualizing aortic disease in patients. With the aid of three-dimensional (3D) image reconstruction, TEE and IVUS can potentially overcome this limitation but still provide only limited spatial appreciation in aortic disease because 3D imaging of the thoracic aorta requires a broader spatial visualization of the mediastinum than provided by both techniques. Moreover, for timely decision making about aortic disease TEE is limited by a large probe, which requires sedation. Therefore, we developed an approach called 3D lighthouse transesophageal echocardiography (LTEE) using a thin intravascular ultrasound catheter, which provides a full circumferential (360 degree) image and requires no sedation. The purpose of this study was to compare the feasibility and accuracy of 3D TEE, 3D IVUS, and 3D LTEE for obtaining spatial visualization of the thoracic aorta to detect aortic diseases in patients. 3D image datasets were obtained for 3D LTEE by a manual pullback of a 3.3 mm thick, 10 MHz intravascular ultrasound catheter positioned in the esophagus; for 3D TEE using a conventional 15 mm thick probe; and for 3D IVUS using a 2.6 mm thick, 20 MHz intravascular ultrasound catheter. In 12 consecutive patients, three with aortic dissection (two with type III, one with type I) and 11 with suspected artherosclerosis, we analyzed and compared spatial visualization of the thoracic aorta, 3D image quality, patient discomfort, and study time. Providing a 3D dataset of 360-degree tomographic images of the mediastinum, 3D LTEE was the only approach that allowed broad spatial visualization of the aortic arch (9 of 12 patients) with the detection of aortic dissection or atherosclerotic plaques. Spatial visualization of the aortic arch by 3D TEE was incomplete because of the relatively narrow 90-degree image sector. However, in other segments 3D image quality by 3D TEE was superior to 3D LTEE and 3D IVUS. Because of the thin catheter, patient discomfort (p < 0.0001) and examination time (p = 0.015) were significantly less for 3D LTEE compared with 3D TEE. 3D LTEE is a promising new technique for 3D imaging of the thoracic aorta and detection of aortic disease with improved spatial visualization and reduced patient discomfort compared with 3D TEE and 3D IVUS.


Wide-field probing of silica laser-induced damage precursors by photoluminescence photochemical quenching.
We describe a wide-field approach to probe transient changes in photoluminescence (PL) of defects on silica surfaces. This technique allows simultaneous capture of spatially resolved PL with spontaneous quenching behavior. We attribute the quenching of PL intensity to photochemical reactions of surface defects and/or subsurface fractures with ambient molecules. Such quenching curves can be accurately reproduced by our theoretical model using two quenchable defect populations with different reaction rates. The fitting parameters of our model are spatially correlated to fractures in silica where point defects and mechanical stresses are known to be present, potentially indicating regions prone to laser-induced damage growth. We believe that our approach allows rapid spatial resolved identification of damage prone morphology, providing a new pathway to fast, non-destructive predictions of laser-induced damage growth.


2-Aminopyridinium-fumarate-fumaric acid (2/1/1).
The title complex, 2C5H7N2+.C4H2O42-.C4H4O4, contains cyclic eight-membered hydrogen-bonded rings involving 2-aminopyridinium and fumarate ions. The fumaric acid molecules and fumarate ions lie on inversion centers and are linked into zigzag chains by O-H...O hydrogen bonds. The dihedral angle between the pyridinium ring and the hydrogen-bonded fumarate ion is 7.60 (4) degrees. The fumarate anion is linked to the pyridinium cations by intermolecular N-H...O hydrogen bonds. The heterocycle is fully protonated, thus enabling amine-imine tautomerization.


Genome-Wide Identification and Expression Analysis of ACTIN Family Genes in the Sweet Potato and Its Two Diploid Relatives.
ACTINs are structural proteins widely distributed in plants. They are the main components of microfilaments and participate in many crucial physiological activities, including the maintenance of cell shape and cytoplasmic streaming. Meanwhile, ACTIN, as a housekeeping gene, is widely used in qRT-PCR analyses of plants. However, ACTIN family genes have not been explored in the sweet potato. In this study, we identified 30, 39, and 44 ACTINs in the cultivated hexaploid sweet potato (Ipomoea batatas, 2n = 6x = 90) and its two diploid relatives, Ipomoea trifida (2n = 2x = 30) and Ipomoea triloba (2n = 2x = 30), respectively, via analysis of their genome structure and by phylogenetic characterization. These ACTINs were divided into six subgroups according to their phylogenetic relationships with Arabidopsis thaliana. The physiological properties of the protein, chromosome localization, phylogenetic relationship, gene structure, promoter cis-elements, protein interaction networks, and expression patterns of these 113 ACTINs were systematically investigated. The results suggested that homologous ACTINs are differentiated in the sweet potato and its two diploid relatives, and play various vital roles in plant growth, tuberous root development, hormone crosstalk, and abiotic stress responses. Some stable ACTINs that could be used as internal reference genes were found in the sweet potato and its two diploid relatives, e.g., IbACTIN18, -20, and -16.2; ItfACTIN2.2, -16, and -10; ItbACTIN18 and -19.1. This work provides a comprehensive comparison and furthers our understanding of the ACTIN genes in the sweet potato and its two diploid relatives, thereby supplying a theoretical foundation for their functional study and further facilitating the molecular breeding of sweet potatoes.


Spectrum of VP1 region genetic variants in the foot-and-mouth disease virus serotype O populations derived from infected cattle tongue epithelium.
RNA virus population exists as a complex distribution of non-identical but closely related sequences known as viral quasispecies. Variant strains are selected from this quasispecies population in response to changing environment. The quasispecies dynamics of a virus existing within an infected host differs from that in a cell culture-adapted population. This study was carried out to explore the genetic variations present in the VP1 coding region of the foot-and-mouth disease (FMD) virus serotype O derived directly from infected cattle tongue epithelium. Molecular clonal populations of two serotype O strains belonging to lineages Ind2001 (IND 30/2011) and PanAsia2 (IND 5/2011) were sequenced at VP1 coding region. For IND 30/2011, 19 clones were sequenced and analysis showed variations at 12 nucleotide positions (nt) resulting in 8 amino acid (aa) replacements. Similarly, for IND 5/2011 virus, 18 clones were sequenced, of which six showed nt variations leading to 3 aa replacements. Most of the variable positions mapped to the surface-exposed loops and some of them were found in the neutralizing antigenic sites (position 81, 149, 169, 186 and 202 of IND 30/2011 and 141 of IND 5/2011), which potentially could be beneficial in rapid adaptive evolution of the virus by giving rise to antigenic variants to overcome neutralizing antibodies. These findings encourage further research into the landscape of the viral quasispecies population in vivo and its implication for viral ecology.


What representations and computations underpin the contribution of the hippocampus to generalization and inference?
Empirical research and theoretical accounts have traditionally emphasized the function of the hippocampus in episodic memory. Here we draw attention to the importance of the hippocampus to generalization, and focus on the neural representations and computations that might underpin its role in tasks such as the paired associate inference (PAI) paradigm. We make a principal distinction between two different mechanisms by which the hippocampus may support generalization: an encoding-based mechanism that creates overlapping representations which capture higher-order relationships between different items [e.g., Temporal Context Model (TCM): Howard et al., 2005]-and a retrieval-based model [Recurrence with Episodic Memory Results in Generalization (REMERGE): Kumaran and McClelland, in press] that effectively computes these relationships at the point of retrieval, through a recurrent mechanism that allows the dynamic interaction of multiple pattern separated episodic codes. We also discuss what we refer to as transfer effects-a more abstract example of generalization that has also been linked to the function of the hippocampus. We consider how this phenomenon poses inherent challenges for models such as TCM and REMERGE, and outline the potential applicability of a separate class of models-hierarchical Bayesian models (HBMs) in this context. Our hope is that this article will provide a basic framework within which to consider the theoretical mechanisms underlying the role of the hippocampus in generalization, and at a minimum serve as a stimulus for future work addressing issues that go to the heart of the function of the hippocampus.


Identification of green energy ranunculaceous flora of district Chitral, Northern Pakistan using pollen features through scanning electron microscopy.
Pollen micro-morphological features have proven to be helpful for the plant taxonomists in the identification and classification of plants. The utilization of this plantmayhelpfulin the areas of lignocellulosic conversion to biofuels and diversify application toward biomass. The current study was planned with the aim to evaluate the pollen features of complex Ranunculaceous flora of District Chitral, Northern Pakistan using both scanning electron microscopy (SEM) and Light Microscope (LM) for their taxonomic importance. Pollens of 18 Ranunculaceous species belonging to 6 genera were collected from different localities of the research area. SEM and LM were used to examine both qualitative and quantitative micro-morphological features. Sculptring of the sexine include; Scabrate, psilate, echinate, verrucate, perforate gemmate, and reticulate and so forth. Shape of the pollens was sub-spheroidal, spheroidal, prolate, subprolate and oblate and so forth. Type of pollen was ranged from mono to tricolpate and tricolporate. Quantitative characters include length/width of the pollen, colpus, exine thickness, and P/E ratio. Based on these micro-morphological features a taxonomic key was prepared for the fast and correct identification. RESEARCH HIGHLIGHT: Study of the pollen micro-morphological features of Ranunculaceous species by SEM and LM. Analysing both qualitative and quantitative characters of the pollens. Preparation of taxonomic key based on micro-morphological features for the correct and fast identification.


Systems Pharmacology-Based Discovery of Natural Products for Precision Oncology Through Targeting Cancer Mutated Genes.
Massive cancer genomics data have facilitated the rapid revolution of a novel oncology drug discovery paradigm through targeting clinically relevant driver genes or mutations for the development of precision oncology. Natural products with polypharmacological profiles have been demonstrated as promising agents for the development of novel cancer therapies. In this study, we developed an integrated systems pharmacology framework that facilitated identifying potential natural products that target mutated genes across 15 cancer types or subtypes in the realm of precision medicine. High performance was achieved for our systems pharmacology framework. In case studies, we computationally identified novel anticancer indications for several US Food and Drug Administration-approved or clinically investigational natural products (e.g., resveratrol, quercetin, genistein, and fisetin) through targeting significantly mutated genes in multiple cancer types. In summary, this study provides a powerful tool for the development of molecularly targeted cancer therapies through targeting the clinically actionable alterations by exploiting the systems pharmacology of natural products.


Immediate versus deferred stenting for patients undergoing primary or emergent percutaneous coronary intervention: Protocol for a systematic review and meta-analysis.
Primary or emergent percutaneous coronary intervention (PCI) with stenting is the standard treatment for patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI acute coronary syndromes (ACS) at high risk. The value of delayed stenting following balloon-facilitated reperfusion in these patients is largely unknown. This systematic review aims to assess whether delayed stenting (vs immediate stenting) improves angiographic and cardiovascular clinical outcomes for patients with STEMI or non-STEMI ACS undergoing primary or emergent PCI. The primary endpoint is adverse angiographic outcomes (no or slow coronary flow after final PCI), the main secondary endpoint includes a composite of long-term (≥6 months) all-cause mortality, recurrent ACS (recurrent myocardial infarction, unplanned revascularization of the target vessel, etc.), hospital admission for heart failure or any other cardiovascular cause. Relevant studies will be searched in the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and other electronic databases. Two authors will independently screen studies for inclusion, consulting with a third author where necessary to resolve discrepancies. The risk of bias of included studies will be assessed using the Cochrane Collaboration risk of bias tool, and quality of evidence using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. Results will be presented using risk ratios with 95% confidence interval (CI) for dichotomous outcomes and standardized mean differences with 95% CI for continuous outcomes. This systematic review and meta-analysis protocol will not require ethical approval. We will disseminate the findings of this systematic review and meta-analysis via publications in peer-reviewed journals.


Imaging of the peripheral retina.
The technical progress of the recent years has revolutionized imaging in ophthalmology. Scanning laser ophthalmoscopy (SLO), digital angiography, optical coherence tomography (OCT), and detection of fundus autofluorescence (FAF) have fundamentally changed our understanding of numerous retinal and choroidal diseases. Besides the tremendous advances in macular diagnostics, there is more and more evidence that central pathologies are often directly linked to changes in the peripheral retina. This review provides a brief overview on current posterior segment imaging techniques with a special focus on the peripheral retina.


[Peripheral vertigo versus central vertigo. Application of the HINTS protocol].
One of the most important dilemmas concerning vertigo in emergency departments is its differential diagnosis. There are highly sensitive warning signs in the examination that can put us on the path towards finding ourselves before a case of central vertigo. To determine how effective the application of the HINTS protocol is in the diagnosis of cerebrovascular accidents that mimics peripheral vertigo. We conducted a descriptive observation-based study on patients admitted to hospital with a diagnosis of acute vestibular syndrome in the emergency department. All the patients were monitored on a day-to-day basis until their symptoms improved, with information about nystagmus, the oculocephalic manoeuvre and the skew test. The results from the magnetic resonance imaging study were compared with the alteration of any of those three signs during the time the patient was hospitalised. Altogether 91 patients were examined, with a mean age of 55.8 years. A cerebrovascular accident was observed in eight cases. Of these (mean age: 71 years), in seven of them there were alterations in some of the HINTS signs, and in one case the study was normal (sensitivity: 0.88; specificity: 0.96). All of them had some vascular risk factor. Faced with a patient who visits the emergency department with an acute vestibular syndrome, a suitably directed examination is essential to be able to establish the differential diagnosis between peripheral and central pathology, since some cerebrovascular accidents can present with the appearance of acute vertigo. Applying a protocol like HINTS makes it possible to suspect the central pathology with a high degree of sensitivity and specificity.


Local cost minimization in ant transport networks: from small-scale data to large-scale trade-offs.
Transport networks distribute resources and information in many human and biological systems. Their construction requires optimization and balance of conflicting criteria such as robustness against disruptions, transport efficiency and building cost. The colonies of the polydomous Australian meat ant Iridomyrmex purpureus are a striking example of such a decentralized network, consisting of trails that connect spatially separated nests. Here we study the rules that underlie network construction in these ants. We find that a simple model of network growth, which we call the minimum linking model (MLM), is sufficient to explain the growth of real ant colonies. For larger networks, the MLM shows a qualitative similarity with a Euclidean minimum spanning tree, prioritizing cost and efficiency over robustness. We introduce a variant of our model to show that a balance between cost, efficiency and robustness can be also reproduced at larger scales than ant colonies. Remarkably, such a balance is influenced by a parameter reflecting the specific features of the modelled transport system. The extended MLM could thus be a suitable source of inspiration for the construction of cheap and efficient transport networks with non-zero robustness, suggesting possible applications in the design of human-made networks.


[High prevalence of Down syndrome in the Rancagua Hospital in central Chile].
The Latin American Collaborative Study for Congenital Malformations (ECLAMC) has detected a higher incidence of Down syndrome in a zone of central Chile than in the rest of the country. To analyze the incidence rates of Down syndrome between 1997 and 2003 at the Regional Hospital of Rancagua, located 90 km south of Santiago, Chile. The information obtained by ECLAMC was used. This program, using a case control methodology, registers all newborns with congenital malformations and assigns, as a control, the next normal newborn of the same sex. During the study period, 106 newborns with Down syndrome were registered, with a mean rate of 29.61 per 10,000 live births, twice higher than expected. The rate variations along the years of study suggest a cyclic change, with a hemicycle of six years. In this hospital, mothers under 35 years of age, have twice the risk of having a child with Down syndrome, than in the rest of the country.


Metabolic pathways further increase the complexity of cell size control in budding yeast.
How organisms regulate their size is a major question in biology. With a few notable exceptions (such as cell divisions in the early embryo), most cells need to reach a critical size in order to initiate a new cell cycle. How cells set a critical cell size, and how they know it has been reached, is not well understood. Using various types of experimental systems, decades ago two main models were proposed for cell size homeostasis: the deterministic model and the probabilistic model.


Carvacryl acetate nanoencapsulated with chitosan/chichá gum exhibits reduced toxicity in mice and decreases the fecal egg count of sheep infected with gastrointestinal nematodes.
The nanoencapsulation of biocomposites with anthelmintic action has been proposed as an alternative for improving their efficiency. Thus, the current study aimed to evaluate the efficacy of carvacryl acetate nanoencapsulated with biopolymers (nCVA) in the control of sheep gastrointestinal nematodes. CVA was nanoencapsulated with chitosan/chichá gum and characterized in terms of its efficacy of encapsulation (EE), yield and zeta potential. The acute toxicity of nCVA was evaluated in mice. For the fecal egg count reduction test, 40 animals were divided into four groups (n = 10) and orally administered the following treatments: G1, 250 mg kg−1 CVA; G2, 250 mg kg−1 nCVA; G3, chitosan/chichá gum (negative control) and G4, 2.5 mg kg−1 monepantel (positive control). Feces were collected on days 0 and 16 posttreatment to determine the eggs per gram of feces (epg). The EE and yield of nCVA were 72.8 and 57.5%, respectively. The nanoparticles showed a size of 764.5 ± 302.5 nm, and the zeta potential at pH 3.2 was +22.0 mV. nCVA presented a 50% lethal dose (LD50) of 2609 mg kg−1. By 16 days posttreatment, CVA, nCVA and monepantel reduced the epg by 52.9.7, 71.5 and 98.7%, respectively, and the epg of sheep treated with nCVA differed from that of the negative control (P > 0.05) but did not differ from that of sheep treated with CVA. In conclusion, the nanoencapsulation of CVA reduced its toxicity, and nCVA showed anthelmintic activity.


Abnormalities of C-Kit-positive cellular network in isolated hypoganglionosis.
C-Kit-positive interstitial cells of Cajal (ICCs) have a key role in the normal motility function and development of the bowel. They are pacemaker cells, which facilitate active propagation of electrical events and neurotransmission in the bowel wall. ICCs are present in the bowel as myenteric ICCs (ICC(my)S) and muscular ICCs (ICC(mus)S). The aim of this study was to examine the distribution of c-Kit-positive ICCs and their relationship to the autonomic intrinsic innervation in bowel specimens from patients with isolated hypoganglionosis. Full-thickness large bowel specimens were obtained from 6 patients with hypoganglionosis and from 4 patients during bladder augmentation (controls). Frozen sections and whole-mount preparations were stained using c-Kit immunohistochemistry, nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase, and acetylcholinesterase (AChE) histochemistry and evaluated using normal brightfield and confocal laser scanning microscopy. NADPH-diaphorase and AChE histochemistry findings showed characteristic histologic features of hypoganglionosis, eg, sparse and small myenteric ganglia and low or absent AChE activity in the lamina propria. Myenteric plexus in the normal bowel was surrounded by a dense network of c-Kit-positive ICC(my)S, whereas in hypoganglionosis sparse isolated ICC(my)S were found. C-Kit-positive ICC(mus)S were reduced markedly in the longitudinal and circular muscle layer and at the innermost part of the circular muscle in hypoganglionosis. Deficient expression of c-Kit-positive myenteric and muscular ICCs in the hypoganglionic colon may contribute to the motility dysfunction in the affected bowel.


Porphyrin-templated synthetic G-quartet (PorphySQ): a second prototype of G-quartet-based G-quadruplex ligand.
Template-assembled synthetic G-quartet (TASQ) has been reported recently as a G-quadruplex ligand interacting with DNA according to an unprecedented, nature-inspired 'like likes like' approach, based on the association between two G-quartets, one being native (quadruplex) and the other one artificial (ligand). Herein, a novel TASQ-based ligand is designed, synthesized and its quadruplex-recognition properties are evaluated in vitro: PorphySQ (for porphyrin-templated synthetic G-quartet) displays enhanced quadruplex recognition properties as compared to the very first reported prototype (DOTASQ, for DOTA-templated synthetic G-quartet), since the porphyrin template insures a more stable intramolecular G-quartet fold due to self-stabilizing interactions that may take place intramolecularly between the porphyrin ring and the formed G-quartet.


Synthesis and characterization of a chromium(V) cis-dioxo bis(1,10-phenanthroline) complex and crystal and molecular structures of its chromium(III) precursor.
The first structurally characterized Cr(V) dioxo complex, cis-[CrV(O)2(phen)2](BF4) (2, phen=1,10-phenanthroline) has been synthesized by the oxidation of a related Cr(III) complex, cis-[Cr(III)(phen)2(OH2)2](NO3)3.2.5H2O (1, characterized by X-ray crystallography), with NaOCl in aqueous solutions in the presence of excess NaBF4, and its purity has been confirmed by electrospray mass spectrometry (ESMS), EPR spectroscopy, and analytical techniques. Previously reported methods for the generation of Cr(V)-phen complexes, such as the oxidation of 1 with PbO2 or PhIO, have been shown by ESMS to lead to mixtures of Cr(III), Cr(V), Cr(VI), and in some cases Cr(IV) species, 3. Species 3 was assigned as [CrIV(O)(OH)(phen)2]+, based on ESMS and X-ray absorption spectroscopy measurements. A distorted octahedral structure for 2 (CrO, 1.63 A; Cr-N, 2.04 and 2.16 A) was established by multiple-scattering (MS) modeling of XAFS spectra (solid, 10 K). The validity of the model was verified by a good agreement between the results of MS XAFS fitting and X-ray crystallography for 1 (distorted octahedron; Cr-O, 1.95 A; Cr-N, 2.06 A). Unlike for the well-studied Cr(V) 2-hydroxycarboxylato complexes, 2 was equally or more stable in aqueous media (hours at pH=1-13 and 25 degrees C) compared with polar aprotic solvents. A stable Cr(III)-Cr(VI) dimer, [Cr(III)(Cr(VI)O4)(phen)2]+ (detected by ESMS), is formed during the decomposition of 2 in nonaqueous media. Comparative studies of the oxidation of 1 by NaOCl or PbO2 have shown that [Cr(V)(O)2(phen)2]+ was the active species responsible for the previously reported oxidative DNA damage, bacterial mutagenicity, and increased incidence of micronuclei in mammalian cells, caused by the oxidation products of 1 with PbO2. Efficient oxidation of 1 to a genotoxic species, [Cr(V)(O)2(phen)2]+, in neutral aqueous media by a biological oxidant, hypochlorite, supports the hypothesis on a significant role of reoxidation of Cr(III) complexes, formed during the intracellular reduction of Cr(VI), in Cr(VI)-induced carcinogenicity. Similar oxidation reactions may contribute to the reported adverse effects of a popular nutritional supplement, Cr(III) picolinate.


Dynamical and statistical properties of estimated high-dimensional ODE models: The case of the Lorenz '05 type II model.
The performance of estimated models is often evaluated in terms of their predictive capability. In this study, we investigate another important aspect of estimated model evaluation: the disparity between the statistical and dynamical properties of estimated models and their source system. Specifically, we focus on estimated models obtained via the regression method, sparse identification of nonlinear dynamics (SINDy), one of the promising algorithms for determining equations of motion from time series of dynamical systems. We chose our data source dynamical system to be a higher-dimensional instance of the Lorenz 2005 type II model, an important meteorological toy model. We examine how the dynamical and statistical properties of the estimated models are affected by the standard deviation of white Gaussian noise added to the numerical data on which the estimated models were fitted. Our results show that the dynamical properties of the estimated models match those of the source system reasonably well within a range of data-added noise levels, where the estimated models do not generate divergent (unbounded) trajectories. Additionally, we find that the dynamics of the estimated models become increasingly less chaotic as the data-added noise level increases. We also perform a variance analysis of the (SINDy) estimated model's free parameters, revealing strong correlations between parameters belonging to the same component of the estimated model's ordinary differential equation.


Diagnosis of human immunodeficiency virus infection using citrated whole blood.
Standard isolation of human immunodeficiency virus type 1 (HIV-1) from peripheral blood mononuclear cells (PBMC) requires 5 to 20 ml of blood, and the centrifugal separation of PBMC is expensive and time-consuming. Whole-blood coculture techniques use small sample volumes, do not require centrifugation, and allow measurement of the total viral burden in peripheral circulation. We compared the results of citrated whole-blood coculture with those obtained by the standard AIDS Clinical Trials Group PBMC semiquantitative culture method and reverse transcription-PCR quantitation of plasma HIV-1 RNA levels. PBMC cocultures were also set up with added erythrocytes (RBCs) to determine if the presence of RBCs affects the replication of HIV-1 in vitro. The mean number of cells required for a p24-positive PBMC coculture was approximately seven times greater than that required for a positive citrated whole-blood coculture (P < 0.01). At volumes of 100, 50, and 25 microl, the sensitivities of the whole-blood coculture were 94.5, 93.6, and 87.3%, respectively. The PBMC culture in the presence of added RBCs was more sensitive than PBMC coculture alone. The citrated whole-blood coculture was simple to perform, produced a reliable diagnosis of HIV infection in adult volunteers, was more sensitive than previously reported techniques even in half the culture time, and showed less variability than the PBMC coculture. Citrated whole-blood coculture may be a useful and efficient tool for diagnosing infection with HIV-1.


The structure of the efflux pump AcrB in complex with bile acid.
Gastrointestinal bacteria, like Escherichia coli, must remove bile acid to survive in the gut. Bile acid removal in E. coli is thought to be mediated primarily by the multidrug efflux pump, AcrB. Here, we present the structure of E. coli AcrB in complex with deoxycholate at 3.85 A resolution. All evidence suggests that bile acid is transported out of the cell via the periplasmic vestibule of the AcrAB-TolC complex.


Periodontal regeneration employing gingival margin-derived stem/progenitor cells: an animal study.
This study investigated the periodontal regenerative potential of gingival margin-derived multipotent postnatal stem/progenitor cells. Periodontal defects were induced at six sites in eight miniature pigs in the premolar/molar area (-4 weeks). Autologous cells isolated from the gingival margin were magnetically sorted using STRO-1 antibodies and characterized flow cytometrically for the expression of CD14, CD31, CD34, CD45, CD117 and STRO-1 surface markers. Colony formation and multilineage differentiation potential were tested. The cells were expanded and loaded on deproteinized bovine cancellous bone (DBCB) and Collagen scaffolds. Within every miniature pig, six periodontal defects were randomly treated with loaded-DBCB (test group 1), unloaded-DBCB (control group 1), loaded-Collagen scaffolds (test group 2), unloaded-Collagen scaffolds (control group 1), scaling and root planing (negative control 1) or left untreated (negative control 2). Differences in clinical attachment level (ΔCAL), probing depth (ΔPD), gingival recession (ΔGR) and radiographic defect volume (ΔRDV) between baseline and 12 weeks, as well as histological attachment level (HAL), junctional epithelium length (JE) and connective tissue adhesion (CTA) after 12 weeks were evaluated. Isolated cells showed stem/progenitor cell characteristics. Cell-loaded scaffolds showed higher ΔCAL, ΔPD, ΔGR, HAL and lower JE and CTA compared with unloaded scaffolds and negative controls. The sort of scaffold had no significant influence on the measured outcomes. Gingival margin-derived stem/progenitor cells show significant periodontal regenerative potential.


The role of the institutional review board in the oversight of the ethical aspects of human studies research.
Institutional review boards are charged with overseeing that human studies research is conducted in accordance with federal and state regulations and with their own policies and procedures, with the goal of minimizing risks to participants and maximizing the quality of the research data. Nutrition research often involves vulnerable populations, including children and the cognitively impaired, for whom there are specific regulations. Ethical issues are common in nutrition research, and both the investigative team and the institutional review board should seek input regarding ethical issues that arise.


Power Moderates the Effects of Social Dominance Orientation on Punishment: An Experimental Analysis.
In this study, it was hypothesized that experimentally manipulated levels of power would moderate the association of dispositional social dominance orientation (SDO) with preferences for harsh punishment. In particular, we expected to detect a stronger effect for dispositional SDO in the low-power condition, relying on the notion that low power enhances sensitivity to threats to the status quo, and that high SDO individuals are particularly motivated to enforce hierarchy-enhancing measures as punishment. SDO scores were measured two months prior to the experiment, and then immediately after the experimental session. As expected, preexperimental SDO interacted with the power manipulation. We found stronger preexperimental SDO effects on punishment among low-power participants. We also anticipated and found that individuals high in SDO increased further their postexperimental SDO scores if assigned to a high-power condition. The discussion focuses on the importance of SDO effects among low-status groups and on how situational roles shape dispositional self-descriptions.


The patents on glucocorticosteroids and selected new therapies for the management of asthma in children.
Despite the continuous increase in the prevalence of asthma in the most underdeveloped parts of the world, nowadays, we can generally speak of a better understanding and management of this disease. The remarkable role played by the inflammatory process in asthmatic patients is well known. The aim of most asthma guidelines is to suppress inflammatory process with a combination of anti-inflammatory drugs and immunotherapy. The management of asthma in children is a challenge because of their inability to express warning signs and seek medical attention in a timely manner. Unlike adults, asthmatic children must rely on their parents or caregivers for the administration of asthma medications. This inability to carry and self-administer asthma drugs may increase the risk of non-compliance. Glucocorticosteroids, the most important drugs for patients with asthma, are associated with an increased level of side effects and compliance issues mostly in children. In an attempt to solve that dilemma, emphasis is being placed on the modification of current management tactics and the introduction of other drugs. This review presents more recent patent therapies for the management of asthma in children.


The effect of foot structure on the three-dimensional kinematic coupling behavior of the leg and rear foot.
Differences in foot structures have been reported to account for the large variability in findings in previous studies that have examined the relationship between foot structure and the interdependent rotations of the lower extremity. The purpose of this study was to determine, in individuals with radiographically distinct foot structures, the effect of foot structure on three-dimensional kinematic behavior of the leg and rear foot during running. Based on radiographic measurements, 10 recreational runners were assigned to a low rear-foot group and another 10 recreational runners were assigned to a high rear-foot group. Three-dimensional kinematic data were collected during treadmill running. Individual axis rotations and the "coupled" relationship between the leg and rear-foot segments were defined using a Cardan angle system of three ordered rotations. The predominant rotations suggest a combined subtalar and talocalcaneal joint axis to favor calcaneal eversion and inversion for the low rear-foot group and tibial medial and lateral rotation for the high rear-foot group. Group differences were also found for the coupling ratio, which described the proportion of calcaneal eversion and inversion transferred or coupled to tibial axial rotation. The rotational patterns and coupling response unique to each foot group may enhance our understanding of lower-extremity injuries related to certain foot structures. An assessment of the coupling relationship in combination with traditional frontal-plane measurements may better guide decisions regarding selection of footwear and orthoses.


[Pharmacogenetics I. Concept, history, objectives and areas of study].
There is great interindividual variability in the response to drugs, both in effectiveness and toxicity. Different patients respond differently to the same medication as a consequence of genetic and non-genetic factors. Pharmacogenetics represents the study of the individual pharmacological response based on the genotype. Its objective is to optimize treatment in an individual basis, thereby creating an individualized therapy, more safe and efficient, that will allow the clinician to select the correct drug, at the adequate dose, for the right patient. In the first part of this review we discuss several aspects of the relationship between genetics and therapeutic response, as well as the concept, history, objectives and different areas of study of pharmacogenetics.


A review of clinical evidence to assess differences in efficacy and safety of luteinizing hormone-releasing hormone (LHRH) agonist (goserelin) and LHRH antagonist (degarelix).
Luteinizing hormone-releasing hormone agonist (LHRH-A), goserelin, and antagonist, degarelix, are both indicated for the treatment of advanced prostate cancer (PCa); however, large comparative trials evaluating their efficacy and safety are lacking. In this review, we assessed the available evidence for both the drugs. Although degarelix achieves an early rapid decline in testosterone (T) and prostate-specific antigen (PSA) levels, median T and PSA levels, in addition to prostate volume and International Prostate Symptom Scores, become comparable with goserelin over the remaining treatment period. Degarelix causes no initial flare, therefore it is recommended in patients with spinal metastases or ureteric obstruction. Goserelin achieves lower PSA, improved time to progression, and better survival outcomes when administered adjunctively to radiotherapy compared with radiotherapy alone, with significant results even over long-term follow-up. The evidence supporting adjuvant degarelix use is limited. Goserelin has better injection site safety, single-step delivery, and an efficient administration schedule compared with degarelix, which has significantly higher injection site reactions and less efficient administration mechanism. There is conflicting evidence about the risk of cardiovascular disease (CVD), and caution is required when using LHRH-A in patients with preexisting CVD. There is considerable long-term evidence for goserelin in patients with advanced PCa, with degarelix being a more recent option. The available comparative evidence of goserelin versus degarelix has several inherent limitations related to study design, sample size, conduct, and statistical analyses, and hence warrants robust prospective trials and long-term follow-up.


Automatized smoking-related action schemata are reflected by reduced fMRI activity in sensorimotor brain regions of smokers.
In the later stages of addiction, automatized processes play a prominent role in guiding drug-seeking and drug-taking behavior. However, little is known about the neural correlates of automatized drug-taking skills and drug-related action knowledge in humans. We employed functional magnetic resonance imaging (fMRI) while smokers and non-smokers performed an orientation affordance task, where compatibility between the hand used for a behavioral response and the spatial orientation of a priming stimulus leads to shorter reaction times resulting from activation of the corresponding motor representations. While non-smokers exhibited this behavioral effect only for control objects, smokers showed the affordance effect for both control and smoking-related objects. Furthermore, smokers exhibited reduced fMRI activation for smoking-related as compared to control objects for compatible stimulus-response pairings in a sensorimotor brain network consisting of the right primary motor cortex, supplementary motor area, middle occipital gyrus, left fusiform gyrus and bilateral cingulate gyrus. In the incompatible condition, we found higher fMRI activation in smokers for smoking-related as compared to control objects in the right primary motor cortex, cingulate gyrus, and left fusiform gyrus. This suggests that the activation and performance of deeply embedded, automatized drug-taking schemata employ less brain resources. This might reduce the threshold for relapsing in individuals trying to abstain from smoking. In contrast, the interruption or modification of already triggered automatized action representations require increased neural resources.


Genetic Structure and Selection of a Core Collection for Long Term Conservation of Avocado in Mexico.
Mexico, as the center of origin of avocado (Persea americama Mill.), harbors a wide genetic diversity of this species, whose identification may provide the grounds to not only understand its unique population structure and domestication history, but also inform the efforts aimed at its conservation. Although molecular characterization of cultivated avocado germplasm has been studied by several research groups, this had not been the case in Mexico. In order to elucidate the genetic structure of avocado in Mexico and the sustainable use of its genetic resources, 318 avocado accessions conserved in the germplasm collection in the National Avocado Genebank were analyzed using 28 markers [9 expressed sequence tag-Simple Sequence Repeats (SSRs) and 19 genomic SSRs]. Deviation from Hardy Weinberg Equilibrium and high inter-locus linkage disequilibrium were observed especially in drymifolia, and guatemalensis. Total averages of the observed and expected heterozygosity were 0.59 and 0.75, respectively. Although clear genetic differentiation was not observed among 3 botanical races: americana, drymifolia, and guatemalensis, the analyzed Mexican population can be classified into two groups that correspond to two different ecological regions. We developed a core-collection by K-means clustering method. The selected 36 individuals as core-collection successfully represented more than 80% of total alleles and showed heterozygosity values equal to or higher than those of the original collection, despite its constituting slightly more than 10% of the latter. Accessions selected as members of the core collection have now become candidates to be introduced in cryopreservation implying a minimum loss of genetic diversity and a back-up for existing field collections of such important genetic resources.


IL-4 up-regulates cyclooxygenase-1 expression in macrophages.
Macrophages use various cell-surface receptors to sense their environment and undergo polarized responses. The cytokines, interleukin (IL)-4 and IL-13, released from T-helper type 2 (Th2) cells, drive macrophage polarization toward an alternatively activated phenotype (M2). This phenotype is associated with the expression of potent pro-resolving mediators, such as the prostaglandin (PG) D2-derived cyclopentenone metabolite, 15d-PGJ2, produced by the cyclooxygenase (Ptgs; Cox) pathway. Interestingly, IL-4 treatment of bone marrow-derived macrophages (BMDMs) significantly down-regulates Cox-2 protein expression, whereas Cox-1 levels are significantly increased. This phenomenon not only challenges the dogma that Cox-1 is only developmentally regulated, but also demonstrates a novel mechanism in which IL-4-dependent regulation of Cox-1 involves the activation of the mechanistic target of rapamycin complex (mTORC). Using specific chemical inhibitors, we demonstrate here that IL-4-dependent Cox-1 up-regulation occurs at the post-transcriptional level via the Fes-Akt-mTORC axis. Activation of AMP-activated protein kinase (AMPK) by metformin, inhibition of mTORC by torin 1, or CRISPR/Cas9-mediated genetic knock-out of tuberous sclerosis complex-2 (Tsc2) blocked the IL-4-dependent expression of Cox-1 and the ability of macrophages to polarize to M2. However, use of 15d-PGJ2 partially rescued the effects of AMPK activation, suggesting the importance of Cox-1 in macrophage polarization as also observed in a model of gastrointestinal helminth clearance. In summary, these findings suggest a new paradigm where IL-4-dependent up-regulation of Cox-1 expression may play a key role in tissue homeostasis and wound healing during Th2-mediated immune responses, such as parasitic infections.


[Binding fistulojejunostomy for the treatment of external pancreatic fistula].
To evaluate the safety and feasibility of binding fistulojejunostomy, a new operative procedure, in the treatment of external pancreatic fistula. Eight patients suffering from external pancreatic fistula, 4 males and 4 females, aged 49 (22 approximately 69), underwent binding fistulojejunostomy: 2 cm-length of fistula was isolated and a tube was inserted therein, the jejunum was transected and the distant cut end was everted for the length of 3 cm, the mucosa of the everted jejunum was destroyed with carbolic acid, the everted mucosa of jejunum and the fistula were brought together and sutured with silk, the everted jejunum was then turned back to wrap over the fistula, a silk tie was lopped around the entire circumference of the anastomosis, and lastly, the tube was led out of the abdominal wall. all 8 patients recovered smoothly without pancreatic leakage and other complications. Binding fistulojejunostomy is safe and effective for the treatment of external pancreatic fistula.


Lifelong behavioral and neuropathological consequences of repetitive mild traumatic brain injury.
Exposure to repetitive concussion, or mild traumatic brain injury (mTBI), has been linked with increased risk of long-term neurodegenerative changes, specifically chronic traumatic encephalopathy (CTE). To date, preclinical studies largely have focused on the immediate aftermath of mTBI, with no literature on the lifelong consequences of mTBI in these models. This study provides the first account of lifelong neurobehavioral and histological consequences of repetitive mTBI providing unique insight into the constellation of evolving and ongoing pathologies with late survival. Male C57BL/6J mice (aged 2-3 months) were exposed to either single or repetitive mild TBI or sham procedure. Thereafter, animals were monitored and assessed at 24 months post last injury for measures of motor coordination, learning deficits, cognitive function, and anxiety-like behavior prior to euthanasia and preparation of the brains for detailed neuropathological and protein biochemical studies. At 24 months survival animals exposed to r-mTBI showed clear evidence of learning and working memory impairment with a lack of spatial memory and vestibule-motor vestibulomotor deficits compared to sham animals. Associated with these late behavioral deficits there was evidence of ongoing axonal degeneration and neuroinflammation in subcortical white matter tracts. Notably, these changes were also observed after a single mTBI, albeit to a lesser degree than repetitive mTBI. In this context, our current data demonstrate, for the first time, that rather than an acute, time limited event, mild TBI can precipitate a lifelong degenerative process. These data therefore suggest that successful treatment strategies should consider both the acute and chronic nature of mTBI.


High upper critical fields and evidence of weak-link behavior in superconducting LaFeAsO1-xFx thin films.
Superconducting LaFeAsO1-xFx thin films were grown on single crystalline LaAlO3 substrates with critical temperatures (onset) up to 28 K. Resistive measurements in high magnetic fields up to 40 T reveal a paramagnetically limited upper critical field mu{0}H{c2}(0) around 77 T and a remarkable steep slope of -6.2 T K-1 near T{c}. From transport measurements we observed weak-link behavior in low magnetic fields and evidence for a broad reversible regime.


Intraoperative Parathyroid Autofluorescence Detection in Patients with Primary Hyperparathyroidism.
Intrinsic near-infrared (NIR) autofluorescence of the parathyroid gland may improve intraoperative gland identification without the need for contrast agent injection. Compared with patients undergoing surgery for thyroid disease, identification of pathologic parathyroid tissue in patients with hyperparathyroidism is essential. This study analyzed the utility of a novel real-time autofluorescence imaging system in patients with primary hyperparathyroidism enrolled in a prospective feasibility clinical trial. Data on patients undergoing surgery for primary hyperparathyroidism by two experienced endocrine surgeons were prospectively collected. Intraoperative imaging was performed with a handheld NIR device, and images were captured for analysis. The collected data included the surgeon's confidence in parathyroid identification, both with ambient light and use of NIR imaging, as well as how the imaging affected the surgical procedure. Images were quantified by Image J software, with autofluorescence reported as mean values ± SD. From 2017 to 2018, 59 consecutive patients with a diagnosis of primary hyperparathyroidism underwent resection of 69 parathyroid glands. Use of NIR imaging increased the intraoperative confidence of parathyroid identification (on a scale of 0-5) from an average of 4.1 to an average of 4.4 (+0.3, p = 0.003), all of which were confirmed pathologically. The addition of autofluorescence helped to identify the parathyroid gland in 12 patients (20%), and to rule out other soft tissue as not parathyroid in an additional 9 patients (15%). The mean autofluorescence for the parathyroid in situ (75.9 ± 21.3) was significantly greater than that for the thyroid (61.1 ± 17.4) or soft tissue (53.3 ± 19.2) (p < 0.001 for both). The mean absolute difference in parathyroid versus background thyroid autofluorescence was +15.2 (range, 2.4-53.1). This is the first prospective trial to examine the utility of parathyroid autofluorescence for identifying glands exclusively in patients with parathyroid disease. Intraoperative identification and localization of parathyroid glands by real-time, NIR imaging using their intrinsic autofluorescence is feasible and may provide a useful adjunct during parathyroid surgery.


Sinomenine Inhibits Non-Small Cell Lung Cancer via Downregulation of Hexokinases II-Mediated Aerobic Glycolysis.
Addiction to aerobic glycolysis is a common metabolic phenotype in human non-small cell lung cancer (NSCLC). The natural product Sinomenine (Sin) exhibits significant anti-tumor effects in various human cancers. However, the underlying mechanism remains elusive. The inhibitory effect of Sin on NSCLC cells was determined by MTS and soft agar assays. The glycolysis efficacy of NSCLC cells was examined by glucose uptake and lactate production. The activation of Akt signaling and the protein level of hexokinases II (HK2) were examined by immunoblot (IB), qRT-PCR, and immunohistochemical staining (IHC). The in vivo anti-tumor effect of Sin was validated by the xenograft mouse model. We showed that HK2 is highly expressed in NSCLC tissues and cell lines. Depletion of HK2 suppressed cell viability, anchorage-independent colony formation, and xenograft tumor growth. Sinomenine exhibited a profound inhibitory effect on NSCLC cells by reducing HK2-mediated glycolysis both in vitro and in vivo. Ectopic overexpression of HK2 compromised these anti-tumor efficacies in sinomenine-treated NSCLC cells. Moreover, we revealed that sinomenine decreased Akt activity, which caused the down-regulation of HK2-mediated glycolysis. Knockdown of Akt reduced HK2 protein level and impaired glycolysis. In contrast, overexpression of constitutively activated Akt1 reversed this phenotype. This study suggests that targeting HK2-mediated aerobic glycolysis is required for sinomenine-mediated anti-tumor activity.


CDKL5 localizes at the centrosome and midbody and is required for faithful cell division.
The cyclin-dependent kinase-like 5 (CDKL5) gene has been associated with rare neurodevelopmental disorders characterized by the early onset of seizures and intellectual disability. The CDKL5 protein is widely expressed in most tissues and cells with both nuclear and cytoplasmic localization. In post-mitotic neurons CDKL5 is mainly involved in dendritic arborization, axon outgrowth, and spine formation while in proliferating cells its function is still largely unknown. Here, we report that CDKL5 localizes at the centrosome and at the midbody in proliferating cells. Acute inactivation of CDKL5 by RNA interference (RNAi) leads to multipolar spindle formation, cytokinesis failure and centrosome accumulation. At the molecular level, we observed that, among the several midbody components we analyzed, midbodies of CDKL5-depleted cells were devoid of HIPK2 and its cytokinesis target, the extrachromosomal histone H2B phosphorylated at S14. Of relevance, expression of the phosphomimetic mutant H2B-S14D, which is capable of overcoming cytokinesis failure in HIPK2-defective cells, was sufficient to rescue spindle multipolarity in CDKL5-depleted cells. Taken together, these results highlight a hitherto unknown role of CDKL5 in regulating faithful cell division by guaranteeing proper HIPK2/H2B functions at the midbody.


Complete Genomes of Symbiotic Cyanobacteria Clarify the Evolution of Vanadium-Nitrogenase.
Plant endosymbiosis with nitrogen-fixing cyanobacteria has independently evolved in diverse plant lineages, offering a unique window to study the evolution and genetics of plant-microbe interaction. However, very few complete genomes exist for plant cyanobionts, and therefore little is known about their genomic and functional diversity. Here, we present four complete genomes of cyanobacteria isolated from bryophytes. Nanopore long-read sequencing allowed us to obtain circular contigs for all the main chromosomes and most of the plasmids. We found that despite having a low 16S rRNA sequence divergence, the four isolates exhibit considerable genome reorganizations and variation in gene content. Furthermore, three of the four isolates possess genes encoding vanadium (V)-nitrogenase (vnf), which is uncommon among diazotrophs and has not been previously reported in plant cyanobionts. In two cases, the vnf genes were found on plasmids, implying possible plasmid-mediated horizontal gene transfers. Comparative genomic analysis of vnf-containing cyanobacteria further identified a conserved gene cluster. Many genes in this cluster have not been functionally characterized and would be promising candidates for future studies to elucidate V-nitrogenase function and regulation.


The genetics of fruit flavour preferences.
Intensively bred fruit crops, including tomatoes and strawberries, are widely viewed as lacking flavour. The lack of breeder focus on the consumer is largely due to the genetic complexity of the flavour phenotype as well as a lack of a simple assay that can define consumer preferences. Rapid advances in genomics have opened up new opportunities to understand the chemistry and genetics of flavour. Here, we describe the underlying causes for the loss of flavour in fruits over time and delineate a blueprint for defining the chemistry of consumer liking, reducing that knowledge into a molecular roadmap for flavour improvement.


DNA‑PKcs phosphorylation specific inhibitor, NU7441, enhances the radiosensitivity of clinically relevant radioresistant oral squamous cell carcinoma cells.
Radioresistant cancer cells lead to poor prognosis after radiotherapy. However, the mechanisms underlying cancer cell radioresistance have not been fully elucidated. Thus, the DNA damage response of clinically relevant radioresistant oral squamous cell carcinoma HSC2-R cells, established by long-term exposure of parental HSC2 cells to fractionated radiation, was investigated. The DNA double-strand break (DSB) repair protein-specific inhibitor, NU7441, which targets DNA-dependent protein kinase catalytic subunit (DNA-PKcs) phosphorylation, and IBR2, which targets Rad51, were administered to HSC2 and HSC2-R cells. NU7441 administration eliminated colony formation in both cell lines under 6 Gy X-ray irradiation, whereas IBR2 did not affect colony formation. NU7441 and IBR2 significantly enhanced 6 Gy X-ray irradiation-induced apoptosis in HSC2-R cells. In HSC2-R cells, cell cycle arrest released earlier than in HSC2 cells, and phosphorylated-H2A histone family member X (γH2AX) expression rapidly decreased. Following NU7441 administration, γH2AX expression and the cell percentages of the G2/M phase were not decreased at 48 h after treatment in HSC2-R cells. DNA-PKcs has been demonstrated to regulate non-homologous end-joining (NHEJ) and homologous recombination (HR) repair, and the later phase of DSB repair is dominated by HR. Therefore, the results of the present study indicated that the DSB repair mechanism in HSC2-R cells strongly depends on NHEJ and loss of HR repair function. The present study revealed a potential mechanism underlying the acquired radioresistance and therapeutic targets in radioresistant cancer cells.


Magnetotactic bacteria from Pavilion Lake, British Columbia.
Pavilion Lake is a slightly alkaline, freshwater lake located in British Columbia, Canada (50°51'N, 121°44'W). It is known for unusual organosedimentary structures, called microbialites that are found along the lake basin. These deposits are complex associations of fossilized microbial communities and detrital- or chemical-sedimentary rocks. During the summer, a sediment sample was collected from near the lake's shore, approximately 25-50 cm below the water surface. Magnetotactic bacteria (MTB) were isolated from this sample using a simple magnetic enrichment protocol. The MTB isolated from Pavilion Lake belonged to the Alphaproteobacteria class as determined by nucleotide sequences of 16S rRNA genes. Transmission electron microscopy (TEM) revealed that the bacteria were spirillum-shaped and contained a single chain of cuboctahedral-shaped magnetite (Fe3O4) crystals that were approximately 40 nm in diameter. This discovery of MTB in Pavilion Lake offers an opportunity to better understand the diversity of MTB habitats, the geobiological function of MTB in unique freshwater ecosystems, and search for magnetofossils contained within the lake's microbialites.


Modulation of CYP3a expression and activity in mice models of type 1 and type 2 diabetes.
CYP3A4, the most abundant cytochrome P450 enzyme in the human liver and small intestine, is responsible for the metabolism of about 50% of all marketed drugs. Numerous pathophysiological factors, such as diabetes and obesity, were shown to affect CYP3A activity. Evidences suggest that drug disposition is altered in type 1 (T1D) and type 2 diabetes (T2D). The objective was to evaluate the effect of T1D and T2D on hepatic and intestinal CYP3a drug-metabolizing activity/expression in mice. Hepatic and intestinal microsomes were prepared from streptozotocin-induced T1D, db/db T2D and control mice. Domperidone was selected as a probe substrate for CYP3a and formation of five of its metabolites was evaluated using high performance liquid chromatography. Hepatic CYP3a protein and mRNA expression were assessed by Western blot and reverse-transcription quantitative polymerase chain reaction respectively. Hepatic microsomal CYP3a activity was significantly increased in both T1D and T2D groups versus control group. Intestinal CYP3a activity was also significantly increased in both T1D and T2D groups. Moreover, significant increases of both hepatic CYP3a mRNAs and protein expression were observed in both T1D and T2D groups versus control group. Additional experiments with testosterone further validated the increased activity of CYP3a under the effect of both T1D and T2D. Although differences exist in the pathophysiological insults associated with T1D and T2D, our results suggest that these two distinct diseases may have the same modulating effect on the regulation of CYP3a, ultimately leading to variability in drug response, ranging from lack of effect to life-threatening toxicity.


The case and context for atmospheric methane as an exoplanet biosignature.
Methane has been proposed as an exoplanet biosignature. Imminent observations with the James Webb Space Telescope may enable methane detections on potentially habitable exoplanets, so it is essential to assess in what planetary contexts methane is a compelling biosignature. Methane's short photochemical lifetime in terrestrial planet atmospheres implies that abundant methane requires large replenishment fluxes. While methane can be produced by a variety of abiotic mechanisms such as outgassing, serpentinizing reactions, and impacts, we argue that—in contrast to an Earth-like biosphere—known abiotic processes cannot easily generate atmospheres rich in CH4 and CO2 with limited CO due to the strong redox disequilibrium between CH4 and CO2. Methane is thus more likely to be biogenic for planets with 1) a terrestrial bulk density, high mean-molecular-weight and anoxic atmosphere, and an old host star; 2) an abundance of CH4 that implies surface fluxes exceeding what could be supplied by abiotic processes; and 3) atmospheric CO2 with comparatively little CO.


Risk factors for violence among female forensic inpatients with schizophrenia.
Schizophrenia is associated with a heightened risk of violent behavior. However, conclusions on the nature of this relationship remain inconclusive. Equally, the empirical evidence on female patients with schizophrenia spectrum disorders (SSD) is strongly underrepresented. For this purpose, the first aim of the present retrospective follow-up study was to determine the risk factors of violence in a sample of 99 female SSD patients discharged from forensic psychiatric treatment between 2001 and 2017, using three different measures of violence at varying time points (i.e., violent index offense, inpatient violence, and violent recidivism). Potential risk factors were retrieved from the relevant literature on SSD as well as two violence risk assessment instruments (i.e., HCR-20 V3, FAM). Further, we aimed to assess the predictive validity of the HCR-20 V3 in terms of violent recidivism and evaluate the incremental validity of the FAM as a supplementary gender-responsive assessment. The given results indicate strong heterogeneity between the assessed violence groups in terms of risk factors. Particularly, violence during the index offense was related to psychotic symptoms while inpatient violence was associated with affective and behavioral instability as well as violent ideation/intent, psychotic symptoms, and non-responsiveness to treatment. Lastly, violent recidivism was related to non-compliance, cognitive instability, lack of insight, childhood antisocial behavior, and poverty. Further, the application of the HCR-20 V3 resulted in moderate predictive accuracy (AUC = 0.695), while the supplementary assessment of the FAM did not add any incremental validity. This article provides important insights into the risk factors of violence among female SSD patients while highlighting the importance of differentiating between various forms of violence. Equally, it substitutes the existing evidence on violence risk assessment in female offenders with SSD.


Dermatomal somatosensory evoked potentials: their use in lumbar radiculopathy.
The accurate diagnosis of lumbar radiculopathy secondary to intervertebral disc herniation or spinal stenosis remains a significant problem. Studies have stressed that misdiagnosis of root entrapment significantly contributes to the incidence of failed back syndrome. In an attempt to aid the proper selection of surgical candidates, dermatomal somatosensory evoked potentials ( DSSEP ) have been used in conjunction with standard diagnostic techniques to evaluate our patients. The advantage of this technique lies in the root specificity. The authors studied the DSSEP using two methods. In Method 1, using myelograms as the standard, the accuracy was 85.7%. In Method II, using surgical outcome as the standard, the accuracy was 87.5%. As a result, the authors have found the noninvasive, relatively inexpensive DSSEP to be a useful adjunct in the selection of patients undergoing lumbar spine surgery.


Functional imaging of uptake of radiopharmaceuticals as a method for tumor visualisation in rats.
Dynamic studies of kinetics of 99mTcO4, 57Co-Bleomycin, 67Ga, A2 fraction of 57Co-Bleomycin in Yoshida sarcoma bearing rats were undertaken. Then the regional variations of rate of the initial uptake of a radiopharmaceutical were examined using functional representation of the rate constants as a function of position. It was concluded that--for radiopharmaceuticals with a high initial uptake rate--the method resulted in visualization of tumor and in suppression of the blood background, within five to eight minutes after administration. This approach based on an evaluation of the parameters of the radiopharmaceutical kinetics in organs and tumor makes possible the use of short-lived radionuclides for tumor visualization and could offer some possibilities of distinguishing the tumor from other accumulating organs.


Synthesis and Physicochemical Evaluation of Entecavir-Fatty Acid Conjugates in Reducing Food Effect on Intestinal Absorption.
The oral bioavailability of entecavir (EV), an anti-viral agent commonly prescribed to treat hepatitis B infections, is drastically reduced under a post-prandial state. This is primarily due to its low permeability in the gastrointestinal tract. To reduce the food effect on the intestinal absorption of the nucleotide analogue, four lipidic prodrugs were synthesized via the esterification of the primary alcohol of EV with fatty acids (hexanoic acid, octanoic acid, decanoic acid, and dodecanoic acid). EV-3-dodecanoate (or EV-C12) exhibited high solubility in a fed state simulated intestinal fluid (78.8 μg/mL), with the acceptable calculated logP value (3.62) and the lowest hydrolysis rate (22.5% for 12 h in simulated gastric fluid, pH 1.2). Therefore, it was chosen as a candidate to improve intestinal absorption of EV, especially under a fed state condition. Physical characterization using scanning electron microscopy, a differential scanning calorimeter, and X-ray powder diffraction revealed that EV-C12 had a rectangular-shaped crystalline form, with a melting point of about 170 °C. In a release test in biorelevant media, such as fasted and fed state-simulated intestinal and/or gastric fluid, more than 90% of the prodrug was released within 2 h in all media tested. These data suggest that this lipidic prodrug might have the potential to alleviate the negative food effect on the intestinal absorption of EV with increased therapeutic efficacy and patient compliance.


[Staged Duckett urethroplasty and Byars reconstruction for severe hypospadias with dysplastic glans].
To study the effects of staged Duckett urethroplasty and Byars reconstruction in the treatment of severe hypospadias with dysplastic glans. We retrospectively analyzed the clinical data on 57 cases of severe hypospadias with dysplastic glans treated by two-stage Duckett urethroplasty or Byars reconstruction from September 2015 to May 2020. At stage-Ⅰ treatment, the patients were aged from 5 to 47 (mean 21) months, the diameter of the glans less than 1.4 cm, and the interval between the two stages from 6 to 41 (mean 14) months. The patients underwent Duckett urethroplasty, distal in stage Ⅰ and proximal in stage Ⅱ (group A, n = 25) or Byars reconstruction with the urethral plate in stage Ⅰ and Duplay urethroplasty in stage Ⅱ (group B, n = 32). Postoperative follow-up lasted 12-56 (mean 35) months. After stage Ⅱ surgery, penile straightening and smooth appearance of the graft were achieved in all the patients. Six cases of postoperative complications (24%) were observed in group A, including 4 cases of urinary fistula, 1 case of glans dehiscence, 1 case of urethral diverticulum and 1 case of urethral stricture, while 14 cases (43.8%) were observed in group B, including 9 cases of urinary fistula, 9 cases of glans dehiscence and 2 cases of urethral diverticulum, with a remarkably lower incidence rate of glans dehiscence in group A than in B (P = 0.043), but no statistically significant difference in the other observations between the two groups (P > 0.05). Both staged strategies of Duckett urethroplasty and Byars reconstruction can be used for the treatment of severe hypospadias with dysplastic glans, but the latter may result in a higher incidence rate of glans dehiscence postoperatively and bring more difficulties to subsequent repair.