Mechanism-based and computational modeling of hydrogen sulfide biogenesis inhibition: interfacial inhibition.
Hydrogen sulfide (H2S) is a gaseous signaling molecule that participates in various signaling functions in health and diseases. The tetrameric cystathionine γ-lyase (CSE) contributes to H2S biogenesis and several investigations provide evidence on the pharmacological modulation of CSE as a potential target for the treatment of a multitude of conditions. D-penicillamine (D-pen) has recently been reported to selectively impede CSE-catalyzed H2S production but the molecular bases for such inhibitory effect have not been investigated. In this study, we report that D-pen follows a mixed-inhibition mechanism to inhibit both cystathionine (CST) cleavage and H2S biogenesis by human CSE. To decipher the molecular mechanisms underlying such a mixed inhibition, we performed docking and molecular dynamics (MD) simulations. Interestingly, MD analysis of CST binding reveals a likely active site configuration prior to gem-diamine intermediate formation, particularly H-bond formation between the amino group of the substrate and the O3' of PLP. Similar analyses realized with both CST and D-pen identified three potent interfacial ligand-binding sites for D-pen and offered a rational for D-pen effect. Thus, inhibitor binding not only induces the creation of an entirely new interacting network at the vicinity of the interface between enzyme subunits, but it also exerts long range effects by propagating to the active site. Overall, our study paves the way for the design of new allosteric interfacial inhibitory compounds that will specifically modulate H2S biogenesis by cystathionine γ-lyase.


Trajectories of adherence to extended treatment with warfarin and risks of recurrent venous thromboembolism and major bleeding.
Little is published about warfarin therapy adherence patterns beyond 6 months of initial anticoagulant treatment and their association with effectiveness and safety for patients with venous thromboembolism (VTE). To compare the risks of recurrent VTE and major bleeding during extended treatment between adherence patterns using MarketScan Commercial and Medicare Supplemental databases (2013-2019). In a retrospective cohort study, we included patients with incident VTE who completed an initial 6-month anticoagulant treatment and received either warfarin or no extended therapy. Group-based trajectory models were used to identify distinct extended treatment trajectories. Associations between the trajectories and risk of hospitalization due to recurrent VTE and major bleeding were assessed using inverse probability treatment-weighted Cox proportional hazards models. Compared with no extended treatment, consistently high warfarin adherence was associated with a significantly decreased risk of hospitalization due to recurrent VTE (hazard ratio [HR] = 0.23; 95% CI, 0.12-0.45), but gradually (HR = 0.29; 95CI, 0.08-1.06) or rapidly declining (HR = 0.14; 95% CI, 0.02-1.24) adherence showed no association with the risk of hospitalization due to recurrent VTE. Compared with no extended treatment, warfarin extended therapy was associated with an increased risk of hospitalization due to major bleeding regardless of adherence patterns (consistently high: HR = 2.08; 95% CI, 1.18-3.64, gradually declining: HR = 2.10; 95% CI, 0.74-5.95, and rapidly declining: HR = 9.19; 95% CI, 4.38-19.29). However, compared with rapidly declining adherence, consistently high (HR = 0.23; 95% CI, 0.11-0.47) and gradually declining (HR = 0.23; 95% CI, 0.08-0.64) adherence were associated with decreased risk of hospitalization due to major bleeding. The findings indicated that consistently high adherence to extended warfarin treatment was associated with a decreased risk of hospitalization due to recurrent VTE but an increased risk of hospitalization due to major bleeding compared with no extended treatment.


Rehabilitation After Anterior Cruciate Ligament Injury: Review of Current Literature and Recommendations.
Anterior cruciate ligament reconstruction (ACLR) is a common surgical procedure with an estimated 120,000 cases performed in the USA each year. Physical therapy plays a critical role in the successful recovery of both surgically and non-surgically managed patients. Interestingly, ACL rehabilitation protocols vary greatly with little consensus among practitioners. Nonetheless, there has been agreement over the last decade to shift from conservative, standardized length protocols to more accelerated, individualized protocols that vary in length and modalities based on patient-specific findings and preferences. This review summarizes the most recent trends, opinions, and modalities in ACL rehabilitation research, with a specific focus on novel methods to treat the specific psychosocial needs of ACL deficient patients. We found that new protocols emphasize early weight bearing, open kinetic chain (OKC) exercises, and other alternative modalities such as neuromuscular electrical stimulation and blood flow restriction. We also found a recent trend toward the use of clinical milestones to determine when a patient is ready for the next phase of a "step-up" rehabilitation program. One particularly nascent topic of research is the inclusion of methods to treat the psychosocial impacts of ACL injury, recovery, and the anxiety around return to sport. Rehabilitation strategy has become increasingly patient-dependent, and the new modalities being utilized are accelerating patient recovery. Return to sport is a particularly important factor for many ACLR patients, and recovery has an important psychological component that has only recently been addressed in the literature, with positive preliminary findings.


Elementary school participation in the United States Department of Agriculture's Team Nutrition program is associated with more healthful school lunches.
To assess school-level characteristics associated with Team Nutrition (TN) program participation, and compare the availability of food items in school lunches in participating vs nonparticipating schools. Cross-sectional study with a nationally representative sample of 2,489 elementary schools in the United States. A mail-back survey was used to collect school administrator-reported annual data on availability of selected healthful and unhealthful lunch items between 2006-2007 and 2009-2010. Multivariate regression analyses was used to predict the availability of food items in school lunches based on TN participation. Team Nutrition participation was higher among schools in the south, in rural areas, and in states with stronger nutrition policies. Program participation was higher in schools with mostly low-income students and where a dietitian was on staff. Participating schools were more likely to offer healthful items and less likely to serve unhealthful items during lunch. The TN program has the potential to help schools offer healthier school meals.


Cyclosporin A is superior to cyclophosphamide in children with steroid-resistant nephrotic syndrome-a randomized controlled multicentre trial by the Arbeitsgemeinschaft für Pädiatrische Nephrologie.
First line immunosuppressive treatment in steroid-resistant nephrotic syndrome in children is still open to discussion. We conducted a controlled multicentre randomized open label trial to test the efficacy and safety of cyclosporin A (CSA) versus cyclophosphamide pulses (CPH) in the initial therapy of children with newly diagnosed primary steroid-resistant nephrotic syndrome and histologically proven minimal change disease, focal segmental glomerulosclerosis or mesangial hypercellularity. Patients in the CSA group (n = 15) were initially treated with 150 mg/m(2) CSA orally to achieve trough levels of 120-180 ng/ml, while patients in the CPH group (n = 17) received CPH pulses (500 mg/m(2) per month intravenous). All patients were on alternate prednisone therapy. Patients with proteinuria >40 mg/m(2) per hour at 12 weeks of therapy were allocated to a non-responder protocol with high-dose CSA therapy or methylprednisolone pulses. At week 12, nine of the 15 (60%) CSA patients showed at least partial remission, evidences by a reduction of proteinuria <40 mg/h per m(2). In contrast, three of the 17 (17%) CPH patients responded (p < 0.05, intention-to-treat). Given these results, the study was stopped, in accordance with the protocol. After 24 weeks, complete remission was reached by two of the 15 (13%) CSA and one of the 17 (5%) CPH patients (p = n.s.). Partial remission was achieved by seven of the 15 (46%) CSA and two of the 15 (11%) CPH patients (p <0.05). Five patients in the CSA group and 14 patients in the CPH group were withdrawn from the study, most of them during the non-responder protocol. The number of adverse events was comparable between both groups. We conclude that CSA is more effective than CPH in inducing at least partial remission in steroid-resistant nephrotic syndrome in children.


Deep Reinforcement Learning with Automated Label Extraction from Clinical Reports Accurately Classifies 3D MRI Brain Volumes.
Image classification is probably the most fundamental task in radiology artificial intelligence. To reduce the burden of acquiring and labeling data sets, we employed a two-pronged strategy. We automatically extracted labels from radiology reports in Part 1. In Part 2, we used the labels to train a data-efficient reinforcement learning (RL) classifier. We applied the approach to a small set of patient images and radiology reports from our institution. For Part 1, we trained sentence-BERT (SBERT) on 90 radiology reports. In Part 2, we used the labels from the trained SBERT to train an RL-based classifier. We trained the classifier on a training set of [Formula: see text] images. We tested on a separate collection of [Formula: see text] images. For comparison, we also trained and tested a supervised deep learning (SDL) classification network on the same set of training and testing images using the same labels. Part 1: The trained SBERT model improved from 82 to [Formula: see text] accuracy. Part 2: Using Part 1's computed labels, SDL quickly overfitted the small training set. Whereas SDL showed the worst possible testing set accuracy of 50%, RL achieved [Formula: see text] testing set accuracy, with a [Formula: see text]-value of [Formula: see text]. We have shown the proof-of-principle application of automated label extraction from radiological reports. Additionally, we have built on prior work applying RL to classification using these labels, extending from 2D slices to entire 3D image volumes. RL has again demonstrated a remarkable ability to train effectively, in a generalized manner, and based on small training sets.


Syntheses of three naturally occurring polybrominated 3,3'-bi-1H-indoles.
The naturally occurring polybrominated indoles 2,2',5,5'-tetrabromo-3,3'-bi-1H-indole, 2,2',6,6'-tetrabromo-3,3'-bi-1H-indole, and 2,2',5,5',6,6'-hexabromo-3,3'-bi-1H-indole were synthesized using a palladium catalyzed, carbon monoxide mediated, double reductive N-heterocyclization of 2,3-bis(2-nitro-4(or 5)-bromophenyl)-1,4-butadienes as the key step.


Di-μ-aqua-bis-[aqua-(2,2'-bi-pyridine)(4-nitro-benzoato)cobalt(II)] bis-(4-nitro-benzoate).
The title compound, [Co2(C7H4NO4)2(C10H8N2)2(H2O)4](C7H4NO4)2, consists of a centrosymmetric bimetallic complex charge-balanced by free 4-nitro-benzoate anions. The CoII ion exhibits a distorted cis-CoN2O4 octa-hedral coordination environment and the Co⋯Co separation is 3.326 (2) Å. In the crystal, the dications and anions are linked by O-H⋯O and C-H⋯O hydrogen bonds.


Fine structure of the epicuticle of the desert scorpion, Hadrurus arizonensis, with reference to location of lipids.
The surface and transverse sections of the epicuticle of the desert scorpion, Hadrurus arizonensis, were examined by scanning and transmission electron microscopy, respectively. Sclerite cuticle that was untreated prior to normal EM preparative procedures was compared to cuticle subjected to lipid solvents, high temperature, and concentrated alkali. Surface morphology of untreated intersegmental cuticle was also examined. The epicuticle is composed of four sublayers: outer membrane, outer epicuticle, cuticulin, and the dense homogeneous layer. Lipid solvents did not significantly alter the morphology of any of these layers or the contents of the wax canals that penetrate the cuticulin layer even though the solvents effectively remove lipids from the epicuticle for chemical analysis. The surface of the sclerite cuticle contains amorphous particles, crystalline projections, and scattered openings to dermal gland ducts. Perforations that correspond to the opening of wax canals were faintly visible after extraction of surface waxes and clearly visible after KOH treatment. No openings to dermal gland ducts or wax canals were observed in untreated intersegmental cuticle. However, wax canals are likely obscured by surface waxes similar to those present in sclerite cuticle.


Activation of an interleukin-1-responsive T-cell lymphoma by fixed P388D1 macrophages and an antibody against the Ag:MHC T-cell receptor.
We have characterized the activation of the interleukin 1 (IL-1)-responsive T-cell lymphoma LBRM33-1A5-47 to interleukin 2 (IL-2) production by phytohemagglutinin (PHA) and IL-1. The signal provided by soluble IL-1 could be replaced by fixed P388D1 cells and the signal provided by PHA by a monoclonal antibody directed against an allotypic determinant of the Ag/MHC T-cell receptor (KJ16-133). The signal provided by fixed P388D1 does not appear to be due to alloreactivity. Instead, it appears to be due to a membrane-bound IL-1. The implications of these observations are discussed.


The influence of isolated doses of drugs, feeding and colonic bacterial ureolysis on urea breath test results.
Aim of this work was to improve standardization of the 13C-urea breath test (13C-UBT) by evaluating the effect of drug administration, feeding and colonic ureolysis on the UBT results. Three different studies were performed. First, a 13C-UBT was performed in 41 Helicobacter pylori infected subjects before and after 1 day of therapy with sucralfate (5 g), colloidal bismuth (600 mg), amoxycillin (2.5 g) or omeprazole (40 mg). Second, a 13C-UBT was performed in 10 H. pylori-positive patients after an overnight fast and repeated 2 h after lunch. Finally, a 13C-UBT was carried out in seven healthy volunteers, with breath sampling prolonged to 6 h to investigate colonic bacterial ureolysis. Even a short course of drugs specific for H. pylori may result in a falsely negative 13C-UBT. Feeding does not interfere with the 13C-UBT in infected subjects. No significant 13C-urea breakdown by colonic bacteria is observed during the 13C-UBT when it is prolonged to 6 h. The 13C-urea breath test is a sensitive clinical tool for the non-invasive diagnosis of H. pylori infection. It is unaffected by feeding or colonic ureolysis. However, false negative results are likely even after 1 day of therapy with bactericidal, 'cytoprotective' or antisecretory drugs.


Impact of mercury discharged from submarine volcano on inner bay ecosystems.
Organic mercury, inorganic mercury and total mercury concentrations in phytoplankton (<0.1 mm) and zooplankton (>0.1 mm) collected in Kagoshima Bay, Japan were measured from 2017 to 2019 to estimate the impact of mercury discharged from submarine volcanoes on ecosystems; submarine volcanic activity continues at a depth of 200 m in the inner part of Kagoshima Bay. The total mercury concentrations in phyto- and zooplankton collected by vertical hauling at 0-200 m at just above the submarine volcano were in the range of 0.11-2.0 mg kg-1 (avg. 0.67 mg kg-1) and 0.090-0.56 mg kg-1 (avg. 0.21 mg kg-1), respectively. These values were one order of magnitude higher than the values in plankton collected in the central part of Kagoshima Bay. Organic mercury concentrations in phyto- and zooplankton were <0.010-0.071 mg kg-1 (avg. 0.028 mg kg-1) and 0.012-0.25 mg kg-1 (avg. 0.10 mg kg-1), respectively, for the inner part, and <0.010-0.040 mg kg-1 (avg. 0.010 mg kg-1) and <0.010-0.025 mg kg-1 (avg. 0.012 mg kg-1), respectively, for the central part. The values obtained in the inner part of the bay increased in summer and decreased in winter, which was consistent with changes in seawater mercury concentrations affected by volcanic activity. The organic mercury concentration in zooplankton collected just above the submarine volcano showed a size dependency, and a higher value was observed in the larger size, which suggested that the discharged mercury from the volcano was absorbed and concentrated through the ecosystem.


A real-world evidence of a consecutive treatment of 42 spine-related pain using dorsal root ganglion-pulsed radiofrequency (DRG-PRF).
Spine-related pain is oftentimes not managed satisfactorily by analgesic medications and physiotherapy. Pulsed radiofrequency targeting on dorsal root ganglion (DRG-PRF) is able to precisely relieve pain without permanent damage to nervous tissue. In this article, we provide a short-term result of DRG-PRF for spine-related pain. A retrospective chart review of a consecutive of 42 patients who underwent PRF between 2015-2016 was conducted. All patients had received pharmaceutical treatment or physiotherapy before PRF. The diagnoses included cervicogenic headache, cervicalgia, upper back, middle back and lower back pain with or without radiculopathy. All of them were treated with DRG-PRF according to corresponding segmental dermatomes. Preoperative and postoperative 1-week, 1-month and 3-month numerical rating scale (NRS) and the usage of analgesic medicines were recorded and analyzed. The mean age was 56.9 ± 14.8 years and 50 % of them were men. Seventy-six percent of patients underwent PRF had their pain originated from cervical and lumbar spine. Sixty percent of PRF procedures were to treat new chronic pain (duration less than 6 months). The preoperative NRS was 7.6 ± 1.1; the postoperative 1-week, 1-month and 3-month NRS were 2.5 ± 2.1, 3.0 ± 2.4 and 3.2 ± 2.4, respectively. DRG-PRF provided significantly NRS decrease in spine-related pain (p < 0.001). DRG-PRF also significantly decrease and deescalate the usage of analgesic medicines at postoperative 3 months (p < 0.001). The drop of NRS from preoperative state to postoperative 1 week was more significant in new chronic pain than in established chronic pain group (1.6 ± 1.4 vs. 3.0 ± 2.2, p = 0.015), however, both groups achieved similar pain reduction at postoperative 3 months (3.1 ± 2.2 vs. 3.3 ± 2.7, p = 0.903). No permanent neurological sequela was found, except 2 patients (4.7 %) had transient paresthesia with mild motor weakness after PRF which resolved within hours spontaneously. DRG-PRF significantly decrease NRS and decrease and deescalate the usage of analgesic medicines in post-procedure 3 months in spine-related pain patients. DRG-PRF is effective for both new chronic and established chronic pain, and offers similar pain reduction for patients with radicular or non-radicular pain.


Expression of hypoxia-inducible factors in human endometrium and suppression of matrix metalloproteinases under hypoxic conditions do not support a major role for hypoxia in regulating tissue breakdown at menstruation.
Classical studies in monkeys suggested that menstruation results from vasoconstriction, hypoxia and necrosis. The heterodimeric hypoxia-inducible factor (HIF) complex is critical in oxygen homeostasis via increased stability of HIF-1alpha/2alpha monomers, and these act as markers of hypoxia. We hypothesized that focal hypoxia in perimenstrual endometrium results in locally increased matrix metalloproteinases (MMP), leading to tissue destruction. HIF-1alpha, HIF-2alpha and HIF-1beta were immunolocalized in cycling endometrium. Endometrial stromal cells were cultured under hypoxic and normoxic conditions and MMP measured by zymography and Western blots. HIF-1alpha and HIF-2alpha were detected in only some endometrial samples, and not confined to the perimenstrual tissue. Where present, they were primarily cytoplasmic, not nuclear. HIF-1beta was localized in epithelium, leukocytes and some decidual cells. Cultured endometrial stromal cells responded to hypoxia with increased cellular HIF-1alpha and secreted vascular endothelial growth factor. ProMMP-1 and proMMP-3 production was reduced in response to hypoxia regardless of the steroidal milieu (no added steroids, estrogen or estrogen plus progesterone). Active MMP-2 and membrane type 1 MMP but not proMMP-2 or proMMP-9 production were also inhibited by hypoxia. These results do not support a role for hypoxia in the focally increased production and activation of MMP observed prior to and during menstruation.


Nucleus accumbens surgery for addiction.
Opiate addiction remains intractable in a large percentage of patients, and relapse is the biggest hurdle to recovery because of psychological dependence. Multiple studies identify a central role of the nucleus accumbens (NAc) in addiction; several studies note decreased addictive behavior after interventions in this area. Based on animal experiments, our institute started the clinical trial for the treatment of drug addicts' psychological dependence by making lesions in the bilateral NAc with stereotactic surgery from July 2000. The short-term outcomes were encouraging and triggered rapid application of this treatment in China from 2003 to 2004. However, lack of long-term outcomes and controversy eventually led to halting the surgery for addiction by the Ministry of Health of China in November 2004 and a nationwide survey about it later. Our institute had performed this surgery in 272 patients with severe heroin addiction. The follow-up study showed that the 5-year nonrelapse rate was 58% and the quality of life was significantly improved. Patients had several kinds of side effects, but the incidence rate was relatively low. The patients gradually recovered more than 5 years after the surgery. The side effects did not severely influence an individual's life or work. Nationwide surgery showed that the nonrelapse rate was 50% in the sample of 150 cases, from 1167 patients overall who underwent stereotactic surgery in China. Although sometimes accompanied by neuropsychological adverse events, stereotactic ablation of NAc may effectively treat opiate addiction. Lesion location has a significant impact on treatment efficacy and requires further study. Because ablation is irreversible, the NAc surgery for addiction should be performed with cautiousness, and deep brain stimulation (DBS) is an ideal alternative.


Prevalence and Correlates of Sexual Violence Experienced by Young Adult Black Men Who Have Sex with Men.
Men who have sex with men (MSM) experience high prevalence of sexual violence (SV), and SV has well-documented effects on health. Research gaps are especially evident for young Black MSM (YBMSM), who experience significant HIV disparities and syndemics, including multiple forms of violence victimization. We examined lifetime prevalence of SV (having been forced or frightened into sexual activity) in a cross-sectional sample of YBMSM (N = 1732), and tested associations of demographic, psychosocial, and structural factors using multivariable regression. YBMSM were recruited between 2013 and 2015 using modified venue-based time-location sampling (e.g., at bars and clubs) in Dallas and Houston, Texas. Approximately 17% of YBMSM experienced any SV in their lifetimes. SV was associated with high school non-completion (OR 1.78; 95% CI 1.15-2.77), lower psychological resilience (OR 0.84; 95% CI 0.71-0.98), lifetime history of homelessness (OR 5.52; 95% CI 3.80-8.02), recent financial hardship (OR 2.16; 95% CI 1.48-3.14), and recent transactional sex (OR 3.87; 95% CI 2.43-6.15). We also examined differences by age of SV onset (childhood versus adulthood). YBMSM with adolescent/emerging adult-onset SV may have been more ambivalent in reporting lifetime SV experience, compared to men with childhood-onset SV, and correlates differed by age of onset. Childhood-onset SV was associated with high school non-completion, lower levels of psychological resilience, history of homelessness, recent financial hardship, and recent transactional sex. Adolescent/emerging adult-onset SV was associated with greater depressive symptoms, history of homelessness, and recent financial hardship. There is a need for multi-level approaches to SV prevention and treatment, including services and supports that are culturally-relevant and responsive to the needs of YBMSM.


Subclinical hypothyroidism among infertile women at a tertiary hospital in South-West Nigeria.
Overt thyroid dysfunction is an accepted cause of female infertility. Its milder form, subclinical hypothyroidism have also been implicated as a contributing factor to disturbed reproductive function. To determine the contribution of subclinical hypothyroidism (SCH) to the burden of infertility. This is a cross sectional, comparative study of One hundred and twenty women with primary or secondaryinfertility who presented for evaluation at gynaecological clinic and controls which are clients that came to access Family planning services. The prevalence of infertility among gynaecological patients seen in the clinic was 38.8% (192/495). The prevalence of SCH among the studied infertile women was 11.7% (7/60) compared with 3.3% (2/60) of the control group (p=0.222). The commonest type of infertility was secondary, 76.7% (46/60). All thestudied infertile women with SCH presented with secondary infertility. There was an observed statistically significant difference in the mean serum TSH (3.19±4.38mIU /L vs 1.60±1.22mIU /L) and FT3, FT4 (0.29±0.074ng/dl vs 0.95±0.16ng/dl and 0.33±0.071ng/dl vs 1.09±0.19ng/dl respectively). Subclinical hypothyroidism was found to be higher among infertile women but this finding was not statistically significant, therefore, the routine screening for SCH among infertile women might be unnecessary.


Sialosyl-galactose: a common denominator of Guillain-Barré and related disorders?
The immune reactivity implicated in the pathogenesis of Guillain-Barré syndrome (GBS) and related diseases, which occur following infection with specific strains of Campylobacter jejuni bearing sialylated lipopolysaccharide structures that cross-react with specific gangliosides, is consistent with provocation of inflammation via molecular mimicry. In this review, we have focused upon microbial characteristics and structures, the fine structure of the essential carbohydrate determinants, and the application of our proposed criteria, modified from those of Koch for causation of infectious and of Witebsky for autoimmune diseases, to the circumstance of infectious induction of autoimmune disorder.


Parental mental illness, attendance at preventive child healthcare and dental caries in the offspring: a nation-wide population-based cohort study.
Severe mental illness (SMI) may interfere with parental caregiving practices and offspring development. Adhering to preventive well-child visits and maintaining good oral hygiene during early childhood requires parental involvement. Whether these activities are affected by parental SMI is unclear. The purpose of the present study was to determine whether children exposed to parental SMI are at increased risk of non-attendance to preventive well-child visits and vaccinations at age 0-5 years and of child dental caries experience at age 5 years. Furthermore, interactions between maternal psychiatric and sociodemographic variables in relation to an adverse child outcome were assessed. Data were obtained from national Danish health registers. All children born in Denmark between January 1997 and December 2010 were followed from birth until their 6th birthday. 679,339 children were included in the study (51% male). Of these, 49,059 children (7.8%) had at least one parent with a lifetime SMI diagnosis. Children of parents with SMI had elevated odds of missing well-child visits and vaccinations (OR 1.41; 95% CI 1.39-1.44, p < 0.0001), and of child dental caries (OR 1.58; 95% CI 1.55-1.62, p < 0.0001). In the presence of maternal SMI, low socioeconomic classification and single-mother status added more to the elevated risk than specific maternal diagnosis or timing of last psychiatric contact. Parents with SMI are less compliant with preventive child healthcare activities than parents without SMI. This indicates a need for practical support to these families in order to prevent inequality in health among their offspring.


Glenoid fractures of the shoulder.
Glenoid fractures of the shoulder are uncommon.Any scapular fracture involving the glenoid should be scrutinized carefully for a surgical treatment option.Classification is helpful in deciding the surgical tactic. Cite this article: EFORT Open Rev 2020;5:620-623. DOI: 10.1302/2058-5241.5.190057.


Rheology of human blood, near and at zero flow. Effects of temperature and hematocrit level.
Static normal human blood possesses a distinctive yield stress. When the yield stress is exceeded, the same blood has a stress-shear rate function under creeping flow conditions closely following Casson's model, which implies reversible aggregation of red cells in rouleaux and flow dominated by movement of rouleaux. The yield stress is essentially independent of temperature and its cube root varies linearly with hematocrit value. The dynamic rheological properties in the creeping flow range are such that the relative viscosity of blood to water is almost independent of temperature. Questions raised by these data are discussed, including red cell aggregation promoted by elements in the plasma.


Investigation of the Prevalence, Virulence Genes, and Antibiogram of Motile Aeromonads Isolated from Nile Tilapia Fish Farms in Egypt and Assessment of their Water Quality.
The aquaculture industry is a fast-growing sector in Egypt; however, the progress of this industry is impeded by many challenges such as poor water quality and associated bacterial infections. Among others, Motile Aeromonas Septicemia (MAS), caused by aeromonads, is among the most important bacterial diseases affecting aquaculture due to its zoonotic potential. In the present work, motile aeromonads were isolated from water samples (n= 8) and Nile tilapia (n= 240) in four fish farms (farms I, II, III, and IV) in Kafr El-Sheikh province during the period March to August 2017. This step was followed by investigation of the prevalence and phenotypic, molecular, and histopathological characterization of aeromonads. In addition, antimicrobial susceptibility and virulence gene detection were analyzed. Interestingly, physicochemical water analysis revealed different ranges in relation to the fish farms and seasons. More importantly, Aeromonas isolates were phenotypically identified in 33.3% and 12.5% from fish and water samples, respectively. The highest prevalence of motile aeromonads (46.7%) was recorded from farm IV, and only 12.5% of water samples were positive for them. Out of 80 isolates, 65 (81.25%) were molecularly identified at the genus level using gyrase B (gyrB). The prevalence of the virulence genes detected in the isolated motile aeromonads was aerolysin (aer), 52.2%; elastase (ahp), 26.25%; hemolysin (hyl), 35%; and lipase (lip), 3.75%. The antibiogram profile revealed that the highest resistance of aeromonads isolates (80%) was recorded to chloramphenicol, kanamycin, and azithromycin. Meanwhile, lower resistance levels of 40%, 30%, and 20% were found for streptomycin, cefotaxime, and amoxicillin, respectively. The multiple antibiotic resistance (MAR) index values ranged between 0.27 and 0.82 of motile aeromonads isolates. Furthermore, the histopathological examinations of naturally diseased tilapia revealed widespread hepatocellular necrosis with diffuse, numerous rod-shaped bacteria in liver with melanomacrophages and lymphocytic depletion with edema and hemosiderosis in the spleen. Our findings provide an updated epidemiological baseline for future reference and highlight the likely role of the adverse impact of water quality in the outbreaks of motile aeromonads with special reference to virulence genes and antibiotic resistant traits.


The genome of Schistosoma mansoni: isolation of DNA, its size, bases and repetitive sequences.
DNA has been prepared from adults and cercariae of Schistosoma mansoni utilizing a technique that involves centrifugation through cesium chloride. The DNA isolated from S. mansoni adults and that isolated from cercariae were found to be indistinguishable in all analyses. No modified bases were detected by chromatography or comparative endonuclease restriction. Cot analysis demonstrated that the haploid genome of S. mansoni is 0.26 pg (2.7 X 10(8) base pairs) and that the genome contains both moderately and highly repeated components. Some of the repetitive fraction of DNA consists of tandemly repeated ribosomal genes of which there are 500-1000 copies per genome (1.8-3.6% of the total DNA). Four other non-ribosomal repetitive sequences (comprising at least a further 2.0% of the total DNA) have been isolated from a DNA clone bank and their arrangement within the S. mansoni genome investigated by restriction and Southern blot analysis. These cloned segments of DNA appear in many different locations within the genome and thus are reminiscent of the interspersed DNA sequences described in higher eukaryotic organisms.


Impact of medicine shortages on patients - a framework and application in the Netherlands.
Medicine shortages are often described in plain numbers, suggesting all shortages have a uniform impact. However, some shortages have a direct and serious effect on patients and need a prompt reaction from stakeholders. This study aims to create a broad framework to assess the impact of a shortage. We identified high impact shortages and selected exemplary shortages which we considered our learning cases. From five learning cases, we identified elements that had a potentially profound impact on one or more of these cases. We tested data saturation on the elements with another five test cases. Based on these elements, we created a framework to assess impact of shortages on patients and presented practical examples how to rate these different elements. Subsequently, we visualised the impact of these five learning cases on patients in radar charts. The five elements which we identified as potentially having a large impact were 1) alternative product, 2) disease, 3) susceptibility, 4) costs and 5) number of patients affected. The five learning cases rated high on different elements, leading to diverse and sometimes even opposite patterns of impact. We created a framework for assessing the impact of a medicine shortage on patients by means of five key elements. By rating these elements, an indication of the impact can be obtained.


Current concepts on the management of tooth wear: part 1. Assessment, treatment planning and strategies for the prevention and the passive management of tooth wear.
The aim of this series of four articles on tooth wear management is to provide the reader with the necessary information in order to be able to successfully manage cases of tooth wear, regardless of the cause, severity and location of the wear pattern seen. The content will largely focus on contemporary clinical techniques, illustrated where possible by case examples. Emphasis will be placed on 'additive adhesive techniques' utilising fixed prosthodontic protocols; however, cases of tooth wear amongst partially dentate patients involving the use of removable prostheses will also be described. The importance of patient consent and contingency planning will also be discussed. Paper 1 will describe the assessment of the wear patient, including the rationale for the planning of dental care. Also discussed will be the administration of preventative and passive management strategies for cases displaying tooth wear.


Current and future directions for hospital and physician reimbursement. Effect on the academic medical center.
Profound changes are occurring in the health care system, including a surfeit of physicians, cost containment, and competition. This article addresses the effects of these changes on the academic medical center. It recommends that the faculty of the future will be of two types--clinician-teachers and researcher-teachers--and outlines the qualifications of these faculties. It recommends a proper reward system for clinician-teachers, the reintroduction of part-time faculties, and careful retrenchment in medical school class size and house staff. It calls for teaching hospitals to improve their physical plants and control costs by phasing out programs that are not cost-effective. Universities should consider divesting themselves of university-owned teaching hospitals. Most importantly, local, state, and federal governments and the public must develop a more supportive attitude toward the needs of medical education.


Secondary ozonides of substituted cyclohexenes: a new class of pollutants characterized by collision-induced dissociation mass spectrometry using negative chemical ionization.
Recent studies indicate that secondary ozonides of cyclic alkenes are formed in atmospheric reactions and may be relatively stable. The secondary ozonides (SOZs) of cyclohexene (1), 1-methylcyclohexene (2), 4-isopropyl-1-methylcyclohexene (3) and 4-isopropenyl-1-methylcyclohexene (limonene) (4) have been characterized by rapid gas chromatography electron ionization (EI), negative and positive chemical ionization (CI: ammonia, isobutane and methane) and collision-induced dissociation (CID) mass spectrometry. Both EI and positive CI spectra were found unsuitable for reproducible analysis. However, negative CI showed stable (M-H)(-) ions with minor fragmentation. CID of the (M-H)(-) ions resulted in simple and reproducible fragmentation patterns for all four SOZs with loss of m/z 18, 44 and 60, tentatively assigned as H(2)O, CO(2) and C(2)H(4)O(2) or CO(3), respectively. Thus, negative CI-MS-MS in combination with rapid gas chromatography is the preferred method for identification of secondary ozonides of cyclohexenes.


Tissue distribution, developmental profiles and effect of denervation of enolase isozymes in rat muscles.
The tissue distribution of muscle-type alpha beta and beta beta enolases in rats were determined with the sandwich-type enzyme immunoassay method which utilized the purified antibodies specific to the alpha and to the beta subunit of enolase, and beta-D-galactosidase from Escherichia coli as label. All the tissues examined contained detectable levels of both alpha beta and beta beta enolases. The beta beta enolase was found at high levels in the skeletal muscle tissues (tongue, esophagus, diaphragm and leg muscles) and in the cartilages (xipoid process and auricular cartilage). The alpha beta enolase was distributed at a relatively high concentration in the heart and in the above-mentioned tissues. The beta beta enolase in the leg muscles, diaphragm and tongue was present on the day of birth at a concentration higher than that of the alpha alpha and alpha beta enolases, and its concentration further increased in a manner apparently related to the functional state of each tissue. Denervation of the leg muscles by cutting the sciatic nerve in adult rats resulted in a drastic change in the isozymes profile. The concentration of beta beta enolase in the tibialis anterior gastrocnemius lateralis and extensor digitorum longus (about 800 pmol/mg protein) decreased to about a half in a few weeks after denervation. In contrast, the concentrations of alpha alpha (2 pmol/mg) and alpha beta (80 pmol/mg) usually showed a slight increase by the treatment (alpha alpha, 7 pmol/mg; alpha beta, 100 pmol/mg after 2 weeks). As compared with these three muscles, the soleus had normally a low enolase level and the effect of denervation was less drastic. These results seem to suggest that the concentration of beta beta enolase is closely correlated with the functional state of the muscle tissue.


Changing our minds: the neural bases of dynamic impression updating.
While a great deal of initial work in social neuroscience addressed the functional bases of our first impressions, our social evaluations of other people are anything but static. Just as our impressions can change, so too has our understanding of the neural underpinnings supporting this dynamic form of social learning. First, I review initial neuroimaging work on behavior-based impression updating, which observed that a distributed network of regions works in concert to revise trait representations in light of new behavioral information. Next, I discuss more recent research detailing how the updating process may be influenced by both bottom-up (e.g. experience) and top-down factors (e.g. motivation). Finally, I explore the contributions of more computational work studying similar processes via tasks that model social learning through repeated interactions and feedback-based reinforcement. Taken together, this work illustrates the expansion of our understanding of social impression formation, beyond static initial snapshots and towards a more dynamic process in which our representations of other people are continuously revised and reinterpreted in light of new information.


Over 80% of NotI sites are associated with CpG rich islands in the sequenced human DNA.
Clones containing DNA segments linked to NotI sites are not only useful for ordering the NotI fragments fractionated by pulsed field gel, but also valuable in the search of unknown genes, because they often contain the CpG rich islands and genes related with them. To know the probability of association of NotI sites with CpG rich islands, we screened 5,188 sequences accumulated in DNA data base for the presence of NotI site and examined the distribution of CpGs around them. The sequential calculation of G + C content and frequency of CpG occurrence at each nucleotide position identified the CpG rich domains close to NotI sites in 77 sequences, which corresponds to 84% of total number of candidate sequences. This frequency is consistent well with the prediction that 89% of NotI sites in mammalian genome are likely to be present in CpG rich islands and would stress the importance of cloning of NotI linking sequences for direct isolation of desired genes. Furthermore, 63 islands newly identified in this study should provide a clue for understanding the transcriptional regulation of associated genes.


Vaccinia virus-specific CD8(+) T-cell responses target a group of epitopes without a strong immunodominance hierarchy in humans.
Immunization with vaccinia virus (VACV) resulted in long-lasting protection against smallpox and successful global eradication of the disease. VACV elicits strong cellular and humoral immune responses. Although neutralizing antibody is essential for protection, cellular immunity seems to be more important for recovery from infection in humans. We analyzed the immunodominance hierarchy of 73 previously identified VACV human CD8(+) T-cell epitopes restricted by HLA-A1, -A2, -A3, -A24, -B7, or -B44 alleles or the alleles belonging to one of these supertypes in 56 donors after primary VACV immunization. With the exception of the responses to HLA-A24 supertype-restricted epitopes, there were no consistent patterns of epitope immunodominance among donors sharing the same HLA alleles or supertypes, which is in sharp contrast with the mouse studies. However, we identified 12 epitopes that were recognized by >or=20% of donors sharing the same HLA allele; 6 of these epitopes contributed >or=20% of the total VACV-specific T-cell response in at least one individual. VACV-specific CD8(+) T-cell responses targeted a group of epitopes, "relatively dominant" epitopes, without a strong immunodominance hierarchy in humans, which may be advantageous to humans to prevent the emergence of T-cell escape mutants.


Influence of Weight Loss on Obesity-Associated Complications After Metabolic and Bariatric Surgery in Adolescents.
Following metabolic and bariatric surgery (MBS), most adolescents experience weight loss and improvement of many obesity-associated complications (OACs). The relationship between weight loss and remission of OACs after MBS in adolescents has not been well described. The Teen Longitudinal Assessment of Bariatric Surgery (Teen-LABS) is a multi-institutional prospective observational study of adolescents who underwent MBS between 2007 and 2012. Lower-weight-loss responders (LWLRs) were defined as having <20% total body weight loss (TBWL) and higher-weight-loss responders (HWLRs) were defined as having ≥20% TBWL at 5 years after MBS. The prevalence of OACs was compared at baseline and 5 years after MBS. Both LWLRs (n = 114) and HWLRs (n = 78) lost significant weight within the first year following MBS; however, the TBWL at 5 years for the LWLRs was 8.6% ± 9.5% compared with 33.8% ± 9.2% for the HWLRs. Those in the HWLR group were more likely to experience durable remission of composite dyslipidemia at 5 years, whereas there were no differences between groups in remission rates of all other OACs. Greater weight loss after MBS in adolescents was associated with greater remission of composite dyslipidemia; however, remission of other OACs was not dependent on major sustained weight loss.


Cell stimulation by haemopoietic lymphokines.
Haemopoietic cells appear to respond to two distinct classes of growth factors, cell-bound molecules and lymphokines. Stimulation by lymphokines can be modelled by IL-3-dependent cell lines, and evidence is presented that such stimulation may represent a novel system of cell signalling unrelated to those where stimulation is a progression from a resting cell state into DNA synthesis and mitosis. The concept of a "rolling" cycle is introduced, and discussed in relationship to recent results suggesting that phosphorylation of a specific 33 kDa protein may be part of the control mechanism. Based on responses to different IL-3s, it is suggested that one function of lymphokines is to modulate responses to others by mechanisms other than regulation of receptor expression.


Age-related changes of elements in human corpus callosum and relationships among these elements.
To elucidate compositional changes of the corpus callosum with aging, the authors investigated age-related changes of elements and relationships with their element contents in the corpus callosum. After ordinary dissection by medical students at Nara Medical University was finished, the genu, trunk, and splenium of the corpus callosum were resected from the subjects ranging in age from 58 to 94 years. The element contents of the corpus callosum were determined by inductively coupled plasma-atomic emission spectrometry. The contents of Ca, P, S, Mg, Zn, Fe, and Na did not change significantly in the genu, trunk, and splenium of the corpus callosum with aging. Regarding the relationships among the element contents, significant correlations were found among the contents of Ca, P, S, Mg, and Fe in all of the genu, trunk, and splenium of the corpus callosum with some exceptions.


The primary structure of pig liver thioltransferase.
The complete amino acid sequence of pig liver thioltransferase has been determined. The homogeneous protein was cleaved by trypsin, chymotrypsin, Staphylococcus aureus V8 protease, and cyanogen bromide. The resulting peptides were purified by reversed-phase high performance liquid chromatography and ion-exchange fast protein liquid chromatography. Sequencing of the fragments was achieved with either automated Edman degradation or fast atom bombardment-mass spectrometry. Pig liver thioltransferase is a single polypeptide with 105 amino acid residues and an acetylated glutamine N terminus. The protein has 2 cysteine pairs with sequences of -Cys-Pro-Phe-Cys- and -Cys-Ile-Gly-Gly-Cys-, the first pair of which (Cys22 and Cys25) is located at the potential active site of the enzyme. The sequence of pig liver thioltransferase displays close homology (82%) with calf thymus glutaredoxin, suggesting that they belong to the same evolutionary family.


Isolation, reactivity, pharmacological activities and total synthesis of hispanolone and structurally related diterpenes from Labiatae plants.
Hispanolone is a furolabdane diterpene isolated from Ballota hispanica, whose natural product chemistry has been summarized and updated here, including several aspects associated with the isolation, structure determination, hemisynthesis, total synthesis, and pharmacology, and related hispanolone diterpenoids that have attracted the interest of different laboratories from diverse perspective and expertise in the last forty-two years.


Bone imaging in prostate cancer: the evolving roles of nuclear medicine and radiology.
The bone scan continues to be recommended for both the staging and therapy response assessment of skeletal metastases from prostate cancer. However, it is widely recognised that bone scans have limited sensitivity for disease detection and is both insensitive and non-specific for determining treatment response, at an early enough time point to be clinically useful. We, therefore, review the evolving roles of nuclear medicine and radiology for this application. We have reviewed the published literature reporting recent developments in imaging bone metastases in prostate cancer, and provide a balanced synopsis of the state of the art. The development of single-photon emission computed tomography combined with computed tomography has improved detection sensitivity and specificity but has not yet been shown to lead to improvements in monitoring therapy. A number of bone-specific and tumour-specific tracers for positron emission tomography/computed tomography (PET/CT) are now available for advanced prostate cancer that show promise in both clinical settings. At the same time, the development of whole-body magnetic resonance imaging (WB-MRI) that incorporates diffusion-weighted imaging also offers significant improvements for detection and therapy response assessment. There are emerging data showing comparative SPECT/CT, PET/CT, and WB-MRI test performance for disease detection, but no compelling data on the usefulness of these technologies in response assessment have yet emerged.


The effects of psychopathology and shame on social representations of health and lifestyle behaviours via free association: a graph analysis approach.
There is a knowledge gap in whether psychopathology aspects can shape and mark the social representations about health and lifestyle. In this work, we investigated the association of psychopathology and shame with the centrality of the words describing eight common social representations of health and lifestyle. A convenience sample of 288 adults participated with an average age of 44.7, and 62.6% were women. The participants were asked to express three consecutive words associated with eight different health and lifestyle experiences by utilizing the free association method. The participants also were completed the Symptom Checklist-90-Revised (SCL-90-R), the Experiences of Shame Scale (ESS), and the Other as Shamer Scale (OAS). Canonical correlation analysis was applied to investigate the relationship between the set of the eight-word centralities and the psycho-demographic variables consisting of the subject's age and gender, the SCL 90 subscales, the OAS, and the ESS. Based on these findings, a structural equation explorative model was formed to test the unidimensionality of the five centralities construct. Τhe psychological characteristics of interpersonal sensitivity, depression, external shame, and hostility were found to affect the word selection process on the social representations concerning nightlife, health, diet, lifestyle, and alcohol consumption. Participants with increased levels of depression tend to choose more centrally positioned words when the stimulus word was diet and more decentralized responses when the stimulus word was health. At the same time, higher external shame corresponded to more decentralized words for the categories of health and lifestyle. Our results indicate that there is a potential interaction between the psychological state and how a social representation of health and lifestyle is constructed through selected words. Graph theory emerged as an additional tool to use to study these relations.


Anticrotalic and antitumoral activities of gel filtration fractions of aqueous extract from Tabernaemontana catharinensis (Apocynaceae).
The high mortality caused by Crotalus durissus terrificus snake venom is mainly due to crotoxin, which acts on the neuromuscular junction inhibiting the mechanism mediating acetylcholine release, thus leading to motor and respiratory paralysis and subsequently to animal death. We recently demonstrated that the aqueous extract (AE) of Tabernaemontana catharinensis can inhibit the lethal activity of C. d. terrificus venom. Eight fractions, PI to PVIII, were obtained by gel filtration of the extract on Sephadex G-10, and assayed for lethality and cytotoxicity. Fraction PVII [2.0 mg/100 g rat/50 microl saline solution (ss)] injected intramuscularly (i.m.) 20 s after the venom (240 microg) or crotoxin (200 microg/50 microl ss) neutralized the lethal activity of 2 LD50 of both. Fractions PI, PVI and PVIII (5.0 mg/100 g rat/50 microl ss) presented potent antitumoral activity in vitro against cells from human breast carcinoma (SK-BR-3) after 24 h incubation, as measured by Mosmann colorimetric method. Fraction PVII contains 12-methoxy-4-methylvoachalotine as its major component. These results demonstrate that the antivenom and antitumoral activities of the AE of T. catharinensis are exerted by different substances present in fraction PVII and fractions PI, PVI and PVIII, respectively, whose characteristics are distinct in terms of staining and Rf when analyzed by thin layer chromatography. The results also show that a preliminary fractionation by Sephadex G-10 gel filtration is a good option as a first step for isolation of biologically active substances from T. catharinensis.


Eco-friendly biosurfactant from Wickerhamomyces anomalus CCMA 0358 as larvicidal and antimicrobial.
Kitchen waste oil (KWO) was evaluated as a substrate for production of biosurfactant by Wickerhamomyces anomalus CCMA 0358 and was tested against Aedes aegypti larvae, the mosquito causing neglected diseases, such as dengue fever, Zika, and Chikungunya, achieving 100 % mortality in the lowest concentration (6.25 %) evaluated in 24 h. Furthermore, possible applications of this compound were evaluated as antibacterial, antiadhesive, and antifungal. At a concentration of 50 %, the biosurfactant was found to inhibit the growth of Bacillus cereus, showing high inhibitions levels against Salmonella Enteritidis, Staphylococcus aureus, and Escherichia coli. The antifungal activity was evaluated against Aspergillus, Cercospora, Colletotrichum, and Fusarium, obtaining results of up to 95 % inhibition. In addition to these promising results, the yeast W. anomalus produced the biosurfactant from an inexpensive substrate, which increases the possibility of its application in several industries owing to the low cost involved.


Molecular quantification for differentiation of fresh and dried Jinqian Baihua She.
Freshly-used crude drugs have unique functions and advantages in TCM practice of treating diseases. Jinlong Capsule is a patent traditional Chinese medicine product effective for treatment of hepatocarcinoma, and fresh Jinqian Baihua She (JBS, the body of juvenile Bungarus multicinctus) is one of its important ingredients. The emergence of counterfeit fresh JBS, often identified as dried JBS with almost identical appearance, poses a difficult problem in the quality control of the product. Herein we report a molecular quantification-based method for differentiation of fresh and dried JBS by determining the copy number of a specific DNA marker in the samples. Using species-specific primers and TaqMan probes, we established a real-time quantitative PCR system for amplification of a fragment in the 658-bp cytochrome oxidase subunit I (COI) region from JBS specimens. The amplicon copy number in the muscle tissues ranged from 1.14 × 107 to 4.83 × 107 copies/mg in fresh JBS samples, as compared with 1.13 × 105-8.91 × 106 copies/mg in dried JBS samples. Based upon Fisher discriminant analysis, we used 1.27 × 107 copies/mg as the cut-off value for differentiating fresh and dried JBS, which was validated in the single-blinded validation test of fresh and dried JBS samples. This qPCR system may provide an efficient means for accurate identification of fresh JBS to improve the quality control of the medicinal product.


Platelet-fibrin embolism in a rhesus macaque: angiographic and pathologic studies comparing fluorescein and indocyanine green.
A male rhesus macaque was found to have what appeared to be numerous platelet-fibrin emboli in retinal vessels in the perimacular area. Indocyanine green (ICG) dye fluorescence and fluorescein angiograms of the fundus demonstrated leakage of fluorescein, but not ICG, from the involved arterioles. Histopathologic changes in the eyes included occlusion of retinal and choroidal vessels with platelet-fibrin emboli, inner retinal ischemia, ischemic injury to the parafoveal capillary bed distally to occlusion of precapillary arterioles, and retinal exudate limited to the regions of capillary damage. Differential leakage of fluorescein may be explained by the difference in binding affinities of the 2 dyes to blood protein: 20% to 40% of the circulating fluorescein is unbound, and 98% of ICG is bound to serum albumin. Simultaneously or serially performed angiograms with fluorescent probes of different sizes might be used to obtain a qualitative measure of vascular integrity in persons with embolism, diabetic retinopathy, sickle cell retinopathy, vasculitis, and other disorders known to produce focal retinal and choroidal vascular occlusion.


Platelet-rich plasma versus autologous blood versus steroid injection in lateral epicondylitis: systematic review and network meta-analysis.
Clinical outcomes between the use of platelet-rich plasma (PRP), autologous blood (AB) and corticosteroid (CS) injection in lateral epicondylitis are still controversial. A systematic review and network meta-analysis of randomized controlled trials was conducted with the aim of comparing relevant clinical outcomes between the use of PRP, AB and CS injection. Medline and Scopus databases were searched from inception to January 2015. A network meta-analysis was performed by applying weight regression for continuous outcomes and a mixed-effect Poisson regression for dichotomous outcomes. Ten of 374 identified studies were eligible. When compared to CS, AB injection showed significantly improved effects with unstandardized mean differences (UMD) in pain visual analog scale (VAS), Disabilities of Arm Shoulder and Hand (DASH), Patient-Related Tennis Elbow Evaluation (PRTEE) score and pressure pain threshold (PPT) of -2.5 (95 % confidence interval, -3.5, -1.5), -25.5 (-33.8, -17.2), -5.3 (-9.1, -1.6) and 9.9 (5.6, 14.2), respectively. PRP injections also showed significantly improved VAS and DASH scores when compared with CS. PRP showed significantly better VAS with UMD when compared to AB injection. AB injection has a higher risk of adverse effects, with a relative risk of 1.78 (1.00, 3.17), when compared to CS. The network meta-analysis suggested no statistically significant difference in multiple active treatment comparisons of VAS, DASH and PRTEE when comparing PRP and AB injections. However, AB injection had improved DASH score and PPT when compared with PRP injection. In terms of adverse effects, AB injection had a higher risk than PRP injection. This network meta-analysis provided additional information that PRP injection can improve pain and lower the risk of complications, whereas AB injection can improve pain, disabilities scores and pressure pain threshold but has a higher risk of complications. Level I evidence.


Encapsulation of dopamine within SU-101: insights by computational chemistry.
Encapsulating and protecting dopamine from oxidation is a difficult challenge. We propose to use SU-101 BioMOF as a dopamine host, where we study different adsorption scenarios by a robust computational approach. Our results show that dopamine encapsulation is feasible with the formation of non-covalent interactions within the SU-101 pores. These computational results have been corroborated experimentally.


Effects of high glucose conditions on the expansion and differentiation capabilities of mesenchymal stromal cells derived from rat endosteal niche.
Mesenchymal stromal cells in the endosteal niche lining compact bone (CB-MSCs) represent a heterogeneous population, all of which contribute to bone repair and remodelling. Hyperglycaemia associated with type 2 diabetes mellitus (T2DM) can delay and impair the bone healing process. Therefore, this study investigated the influences of high (25 mM) glucose conditions on CB-MSC populations isolated from male Wistar rats, versus normal (5.5 mM) glucose conditions; in terms of proliferation (population doublings, PDs), senescence characteristics, stem cell marker expression, colony forming efficiencies (CFEs); and osteogenic/adipogenic differentiation, following extended culture in vitro. CB-MSCs under both normoglycaemic and hyperglycaemic conditions demonstrated similar morphologies and rapid exponential growth to >300PDs, although high glucose conditions promoted more rapid and persistent proliferation beyond ~50PDs, with few indications of senescence. Limited senescence was confirmed by minimal SA-β-galactosidase staining, low senescence marker (p53, p21waf1, p16INK4a) expression and positive telomere maintenance marker (rTERT, TR) expression. However, telomere lengths varied throughout culture expansion, with hyperglycaemia significantly reducing telomere lengths at PD50 and PD200. Furthermore, CB-MSCs expanded in normal and high glucose conditions remained non-transformed, exhibiting similar MSC (CD73/CD90/CD105), multipotency (CD146) and embryonic (Slug, Snail) markers throughout extended culture, but negligible hematopoietic (CD34/CD45) or pluripotency (Nanog, Oct4) markers. Hyperglycaemia significantly increased CFEs at PD50 and PD100, which decreased at PD200. CB-MSC osteogenic differentiation was also inhibited by hyperglycaemia at PD15, PD100 and PD200, but not at PD50. Hyperglycaemia inhibited CB-MSC adipogenic differentiation to a lesser extent at PD15 and PD50, with reduced adipogenesis overall at PD100 and PD200. This study demonstrates the limited negative impact of hyperglycaemia on the proliferative and stem cell characteristics of heterogeneous CB-MSC populations, although minor sub-population(s) appear more susceptible to these conditions leading to impaired osteogenic/adipogenic differentiation capabilities. Such findings potentially highlight the impact of hyperglycaemia on CB-MSC bone repair capabilities in situ.


Risk factors in relation to an emergence of bipolar disorder: a systematic review.
There is a consensus that genetic factors are important in the causation of bipolar disorder (BPD); however, little is known about other risk factors in the aetiology of BPD. Our aim was to review the literature on such risk factors - risk factors other than family history of affective disorders - as predictors for the initial onset of BPD. We conducted a literature search using the MEDLINE, PsycINFO and EMBASE databases. We selected factors of interest including demographic factors, factors related to birth, personal, social and family backgrounds, and history of medical conditions. The relevant studies were extracted systematically according to a search protocol. We identified approximately 100 studies that addressed the associations between antecedent environmental factors and a later risk for BPD. Suggestive findings have been provided regarding pregnancy and obstetric complications, winter-spring birth, stressful life events, traumatic brain injuries and multiple sclerosis. However, evidence is still inconclusive. Childbirth is likely to be a risk factor. The inconsistency across studies and methodological issues inherent in the study designs are also discussed. Owing to a paucity of studies and methodological issues, risk factors of BPD other than family history of affective disorders have generally been neither confirmed nor excluded. We call for further research.


Breastfeeding and early childhood caries. Review of the literature, recommendations, and prevention.
Early childhood caries is a chronic disease that affects a child's general state of health. The question of a link between primary tooth caries and breastfeeding has been addressed for many years, with contradictory results. The concomitant decay of primary teeth, effective establishment, or not, of oral hygiene, and alimentary diversification away from breastfeeding are all confounding factors in this topic. The aim of our study was to analyze the links between breastfeeding and the appearance of caries, as described in the scientific literature and in the recommendations of specialist societies. A review of publications written in English and French was carried out, searching for the terms early childhood caries, decay and breastfeeding, focusing on literature reviews and meta-analyses dating from the past 10 years. The PubMed database of the US National Library of Medicine National Institutes of Health (NBCI) was used. Furthermore, a review of specialist dental and pediatric societies was conducted. Breastfeeding until the age of 1 year is not associated with an increased risk of dental caries, and may even provide protection compared with feeding with formula milk. By contrast, infants who are breastfed beyond the age of 12 months demonstrate an increased risk of caries. However, the results derive from heterogeneous studies that do not always take into account contradictory factors such as eating habits of the mother or infant (feeding during the night, number of meals per day, eating sweet foods etc.), dental hygiene, or the sociocultural context. Moreover, the most recent recommendations of pediatric and dental societies advise breastfeeding until the age of 2 years, suggesting that this be accompanied by toothbrushing and better nutrition by reducing the frequency and consumption of sugary foods, aimed at helping parents choose prolonged breastfeeding. Extended breastfeeding is a protective factor for childhood caries under 1 year of age. Beyond 1 year, it is difficult to conclude between protection and aggravation of caries because of the multiplicity of confounding factors such as dietary patterns, which vary depending on countries and families, and problems of oral hygiene. In practical terms, when breastfeeding continues beyond 1 year, consultation with a dentist is necessary for examination and preventive advice regarding dietary practices (especially sugar intake), oral hygiene, or supplementary fluoride.


The effect of acute hypoxemia and hypotension on adenosine-mediated depression of evoked hippocampal synaptic transmission.
The present study was designed to investigate the relative contributions of arterial P(O(2)), local cerebral blood flow, and oxygen delivery to the adenosine A(1) receptor-mediated depression of evoked synaptic transmission recorded in the rat hippocampus. Urethane-anesthetized rats were given a unilateral common carotid artery occlusion and then placed in a stereotaxic apparatus for stimulation and recording of bilateral hippocampal field excitatory postsynaptic potentials (fEPSPs). Arterial blood gases, mean arterial blood pressure (MAP), and bilateral hippocampal blood flow (HBF) were also measured. Arterial P(O(2)), HBF, and oxygen delivery were manipulated using normoxic hypotension, hypoxic hypotension, and hypoxic normotension. Both hypoxic hypotension and normoxic hypotension resulted in decreased HBF, decreased oxygen delivery, and a depression of the evoked fEPSP limited to the hippocampus ipsilateral to the occlusion. The enhanced HBF and oxygen delivery associated with increased MAP resulted in a restoration and maintenance of hippocampal fEPSPs despite sustained hypoxemia. The adenosine A(1) receptor-mediated depression of the fEPSP was more strongly correlated with changes in HBF and oxygen delivery than with arterial P(O(2)). We propose that adenosine plays an important role mediating the depression of neuronal activity associated with reduced oxygen delivery characteristically observed in ischemic brain tissue.


Impact of psychiatric medication co-exposure on Neonatal Abstinence Syndrome severity.
Among opioid-exposed infants, psychiatric medication co-exposure is common. Our objective was to compare Neonatal Abstinence Syndrome (NAS) outcomes based on individual psychiatric medication co-exposures. A retrospective study of 744 opioid-exposed mother-infant dyads from a single institution was performed. Mothers on pharmacotherapy with methadone or buprenorphine at delivery were included. Data were collected on maternal demographics, psychiatric medication use, and NAS outcomes, including any medication treatment, adjunctive medication treatment, length of hospital stay (LOS), and opioid treatment days. The extent to which individual psychiatric medication and polypharmacy exposure were associated with NAS outcomes was assessed using multivariable regression. Fifty-four percent of the mothers were on ≥1 psychiatric medication, with 32% on ≥2 or psychiatric medications (polypharmacy group). In adjusted models, polypharmacy exposure was associated with longer LOS (β = 4.31 days, 95% CI 2.55-6.06) and opioid treatment days (β = 3.98 days, 95% CI 2.24-5.72) and more treatment with adjunctive medication for NAS (aOR = 2.49, 95% CI 1.57-3.95). Benzodiazepines were associated with longer LOS (β = 4.94, 95% CI 2.86-7.03) and opioid treatment days (β = 4.86, 95% CI 2.61-6.75), and more adjunctive medication treatment (aOR = 2.57, 95% CI 1.49-4.42). Gabapentin was associated with longer LOS (β = 2.79, 95% CI 0.54-5.03), more NAS medication treatment (aOR = 2.96, 95% CI 1.18-7.42) including more adjunctive medications (aOR = 1.92, 95% CI 1.05-3.53). For infants of mothers with OUD who are also on concurrent psychiatric medications, polypharmacy was associated with worse NAS severity. When medically indicated, limiting use of multiple psychiatric medications, particularly benzodiazepines and gabapentin, during pregnancy should be considered to improve NAS outcomes.


Carboxylic acid-functionalized multiwalled carbon nanotubes (COOH-MWCNTs) improved production of atropine in callus of Datura inoxia by influencing metabolism, gene regulation, and DNA cytosine methylation; an in vitro biological assessment.
Atropine is a well-known tropane alkaloid commonly employed in medicine class called anticholinergics. This study intends to address biochemical and molecular responses of Datura inoxia calluses to fortifying culture medium with carboxylic acid-functionalized multi-walled carbon nanotubes (COOH-MWCNTs). The application of MWCNTs influenced callogenesis performance and biomass in a dose-dependent manner. The MWCNT at 5 mgL-1 resulted in the highest biomass of calluses by 57%. While, MWCNTs at high concentrations were accompanied by cytotoxicity. On the other hand, MWCNTs at concentrations above 100 mgL-1 exhibited cytotoxicity, decreased callogenesis performance, and reduced Atropine biosynthesis. The MWCNTs increased the activity of phenylalanine ammonia-lyase (PAL) and catalase enzymes. The concentrations of proline and soluble phenols displayed upward trends in response to using MWCNTs. According to the HPLC assessment, enriching culture medium with MWCNTs at 5 mgL-1 elicited Atropine production in calluses by 64%. The quantitative PCR assessment referred to the upregulation in the transcription of the PAL gene. The expression of ornithine decarboxylase (ODC) and putrescine N-methyltransferase 1 (PMT) genes were also upregulated in calluses cultured in a medium supplemented with MWCNTs. Methylation Sensitive Amplification Polymorphism (MSAP) technique indicated that employing MWCNTs altered the DNA methylation profile, reflecting epigenetic modification. Overall, engineering plant cells with MWCNTs as a nano-elicitor can be suggested for large-scale synthesis of industrially-valuable secondary metabolites.


Monitoring reversion of hepatitis C virus-induced cellular alterations by direct-acting antivirals using cryo soft X-ray tomography and infrared microscopy.
Hepatitis C virus (HCV) is an enveloped RNA virus. One of the hallmarks of HCV infection is a rearrangement of the host cell membranes, known as the `membranous web'. Full-field cryo soft X-ray tomography (cryo-SXT) in the water-window energy range (284-543 eV) was performed on the MISTRAL beamline to investigate, in whole unstained cells, the morphology of the membranous rearrangements induced in HCV replicon-harbouring cells in conditions close to the living physiological state. All morphological alterations could be reverted by a combination of sofosbuvir/daclatasvir, which are clinically approved antivirals (direct-acting antivirals; DAAs) for HCV infection. Correlatively combining cryo-SXT and 2D synchrotron-based infrared microscopy provides critical information on the chemical nature of specific infection-related structures, which allows specific patterns of the infection process or the DAA-mediated healing process to be distinguished.


Purification of uteroglobin using monospecific antibodies coupled to divinylsulphone-activated agarose.
As a model for the isolation of a labile or trace protein, the purification of uteroglobin (UGL) by immunoaffinity chromatography is described. Antibody was isolated from sheep antiserum by immunoprecipitation, and coupled to divinylsulphone-activated agarose (Mini Leak). For the immunoabsorption stage rabbit uterine mucosal scrapings were defatted and incubated directly with the immunosorbent. After washing and desorption, the UGL preparation contained relatively few high molecular weight impurities and these were removed by gel chromatography. Purification was monitored at each step by two-dimensional SDS polyacrylamide gel electrophoresis and immunoelectrophoresis. Furthermore, affinity-purified UGL was tritiated with N-succinimidyl[2,3-3H]propionate and assayed by fluorography. In order to determine absolute UGL concentrations a competitive ELISA was developed.


Ecosystem responses to aquatic invasive species management: A synthesis of two decades of bigheaded carp suppression in a large river.
The invasion of silver carp (Hypophthalmichthys molitrix) and bighead carp (H. nobilis) or "bigheaded carps" has caused extensive ecological and economic harm throughout the Mississippi River and its tributaries. To prevent their continued spread upstream toward the Great Lakes, intense commercial harvest was implemented on the Illinois River, a large tributary that connects the Mississippi River to Lake Michigan. Since implementation, harvest has reduced densities at the invasion front while also presenting an opportunity to generate a synthesis on ecosystem resilience in the face of accelerating invasion. Resilience, the ability of an ecosystem to recover after perturbation, was observed at local scales and within some taxa but has yet to manifest at a river-wide scale and often co-varied with abiotic environmental or seasonal factors. Thus, while intensive harvest has limited further spread of bigheaded carps, and evidence of additional secondary ecosystem benefits exists, opportunities remain to identify potential pathways that could spread such ecosystem benefits even farther.


The Utility of Renal Mass Biopsy in Shared Decision-Making for Renal Mass Treatment.
To evaluate the utility of renal mass biopsy (RMB) in shared decision-making for renal mass treatment. Underutilization of RMB for patients with renal masses is due in part to physicians believing that results have limited clinical utility. This was a prospective study of all patients referred for RMB from October 2019 to October 2021. Patients and physicians completed pre- and post-RMB questionnaires. Questionnaires assessed both parties' perceived utility of RMB and the impact of biopsy results on treatment preference using Likert scales. We enrolled 22 patients with a mean age of 66years (SD 14.5) and mean renal tumor size 3.1 cm (SD 1.4). Five were lost to follow-up (three pre-RMB, two post-RMB). Pre-RMB, 100% of patients believed that a biopsy would help them choose a treatment and 45% were unsure of their treatment preferences. After RMB, 92% perceived their biopsy results as useful and only 9% were unsure of treatment preference. Overall, 100% of patients were glad they had a biopsy. Results led patients and physicians to change their treatment preference in 57% and 40% of cases, respectively. Patients and physicians disagreed about treatment in 81% of cases prior to biopsy, but in only 25% of cases after biopsy. Discordance between patient and physician treatment preference for renal masses is higher in the absence of RMB data. Select patients are willing to undergo RMB and RMB data can increase patient confidence and comfort in a shared decision-making approach for renal mass treatment.


Performance of biological activated carbon (BAC) filtration for the treatment of secondary effluent: A pilot-scale study.
In addition to the adsorption capability for organic compounds, granular activated carbon (GAC) can also serve as a good media for the growth of microbial communities in biofilters. Despite its potential, the application of BAC filtration for municipal wastewater treatment has been little addressed in the literature. In this context, this paper aimed to investigate BAC filtration as a post-treatment of anaerobic effluent in pilot scale and its performance in removing organic matter and turbidity. Removal efficiencies during the biofilters run times and along biofilters depth were also evaluated. Three BAC filters were evaluated under different operating conditions of filtration rates (from 13 to 32 m d-1) and empty bed contact time (EBCT) (from 45 to 112 min) during 170 days. The lowest filtration rate (13 m d-1) presented the best performance in terms of dissolved organic carbon (DOC) removal (68.2 ± 4.0%), leading to mean DOC effluent concentration of 6.8 ± 0,9 mg L-1. The BAC reached the stability of biological activity from the 63rd day of operation, however, the adsorption process was still occurring contributing to DOC removal. These DOC removals were higher than those results reported in the literature for BAC filters treating drinking water and municipal wastewater. The DOC removal efficiencies were maintained during the filter run times, showing the robustness of the system even after the interference caused by the backwashing process. BAC filtration was also capable of removing turbidity, with removal efficiencies between 84.5 ± 3.6% and 70.63 ± 6.8% depending on the filtration rate. The results indicated the capability of BAC systems to remove efficiently organic carbon and turbidity from effluents with high organic content, mean of 23.97 (±3.96) mg.L-1, and also valuable support to determine adequate operating parameters for BAC filters application in secondary effluent treatment, such as filtration rate (13 m d-1), EBCT (112 min), and detailed backwashing procedures.


Characterization of two high molecular weight catechol-containing glycoproteins from pharate pupal cuticle of the tobacco hornworm, Manduca sexta.
Two high molecular weight cuticular proteins (MSCP120 and MSCP246) were extracted in acidic guanidine hydrochloride solution from tanning abdominal cuticle of Manduca sexta pharate pupae and purified by size exclusion high performance liquid chromatography. The apparent molecular weights were ca. 120 and 246 kDa as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Both proteins contained high levels of glutamate/glutamine, glycine, serine, alanine and aspartate/asparagine. MSCP120 was enriched in histidine relative to MSCP246, but the reverse was true for valine and proline. Small quantities of beta-alanine and 3,4-dihydroxyphenylalanine (DOPA), as well as other catechols and carbohydrates, also were detected in the hydrolysates. The proteins became radiolabeled when [1-14C]-beta-alanine was injected into pharate pupae, presumably by the formation of adducts with N-beta-alanyldopamine metabolites during sclerotization. Mild acid hydrolysis released N-beta-alanylnorepinephrine and 3,4-dihydroxyphenylketoethanol from both proteins. Strong acid hydrolysis yielded predominantly 3,4-dihydroxyphenylketoethylamine (arterenone), but also DOPA and dopamine. The N-terminal amino acid sequences of the two cuticular proteins were dissimilar, and that of MSCP246 was more hydrophobic than MSCP120. Both of these proteins were glycosylated with glucose, N-acetylglucosamine and traces of N-acetylgalactosamine, and MSCP246 also contained galactose. These structural glycoproteins, which occur in cuticle undergoing sclerotization, apparently react post-translationally with quinonoid tanning agents to yield catecholamine-protein adducts. Small amounts of peptidyl DOPA probably are formed by hydroxylation of tyrosyl residues. Results from this study are consistent with the hypothesis that these catechol-containing glycoproteins participate in cross-linking reactions in M. sexta pupal cuticle during sclerotization.


Predicting intersection crash frequency using connected vehicle data: A framework for geographical random forest.
Accurate crash frequency prediction is critical for proactive safety management. The emerging connected vehicles technology provides us with a wealth of vehicular motion data, which enables a better connection between crash frequency and driving behaviors. However, appropriately dealing with the spatial dependence of crash frequency and multitudinous driving features has been a difficult but critical challenge in the prediction process. To this end, this study aims to investigate a new Artificial Intelligence technique called Geographical Random Forest (GRF) that can address spatial heterogeneity and retain all potential predictors. By harnessing more than 2.2 billion high-resolution connected vehicle Basic Safety Message (BSM) observations from the Safety Pilot Model Deployment in Ann Arbor, MI, 30 indicators of driving volatility are extracted, including speed, longitudinal and lateral acceleration, and yaw rate. The developed GRF was implemented to predict rear-end crash frequency at intersections. The results show that: 1) rear-end crashes are more likely to happen at intersections connecting minor roads compared to major roads; 2) a higher number of hard acceleration and deceleration events beyond two standard deviations in the longitudinal direction is a leading indicator of rear-end crashes; 3) the optimal GRF significantly outperforms Global Random Forest, with a 9% lower test error and a substantially better fit; and 4) geographical visualization of variable importance highlights the presence of spatial non-stationarity. The proposed framework can proactively identify at-risk intersections and alert drivers when leading indicators of driving volatility tend to worsen.


Towards rationally designed biomanufacturing of therapeutic extracellular vesicles: impact of the bioproduction microenvironment.
Extracellular vesicles (EVs), including exosomes, microvesicles, and others, have emerged as potential therapeutics for a variety of applications. Pre-clinical reports of EV efficacy in treatment of non-healing wounds, myocardial infarction, osteoarthritis, traumatic brain injury, spinal cord injury, and many other injuries and diseases demonstrate the versatility of this nascent therapeutic modality. EVs have also been demonstrated to be effective in humans, and clinical trials are underway to further explore their potential. However, for EVs to become a new class of clinical therapeutics, issues related to translation must be addressed. For example, approaches originally developed for cell biomanufacturing, such as hollow fiber bioreactor culture, have been adapted for EV production, but limited knowledge of how the cell culture microenvironment specifically impacts EVs restricts the possibility for rational design and optimization of EV production and potency. In this review, we discuss current knowledge of this issue and delineate potential focus areas for future research towards enabling translation and widespread application of EV-based therapeutics.


Choroidal occlusive disease in sickle cell hemoglobinopathies.
Two distinct episodes of posterior ciliary artery occlusion were studied in a 32-year-old man with hemoglobin SS disease and multiple episodes of amaurosis fugax. Although posterior ciliary artery occlusions have been observed following photocoagulation of sickle cell retinopathy, their spontaneous evolution in patients with sickling hemoglobinopathies has received little attention. The manifestations of posterior ciliar artery occlusion seen in this case and in other clinical and experimental situations are reviewed. Histopathologic examination of three additional eyes of patients with sickle hemoglobinopathies revealed changes which may have been the result of previous small posterior ciliary artery occlusions or small vessel occlusive disease related to the sickling hemoglobinopathies; these cases are also reported.


Selective inhibitors of the PSEN1-gamma-secretase complex.
Clinical development of γ-secretases, a family of intramembrane cleaving proteases, as therapeutic targets for a variety of disorders including cancer and Alzheimer's disease was aborted because of serious mechanism-based side effects in the phase III trials of unselective inhibitors. Selective inhibition of specific γ-secretase complexes, containing either PSEN1 or PSEN2 as the catalytic subunit and APH1A or APH1B as supporting subunits, does provide a feasible therapeutic window in preclinical models of these disorders. We explore here the pharmacophoric features required for PSEN1 versus PSEN2 selective inhibition. We synthesized a series of brain penetrant 2-azabicyclo[2,2,2]octane sulfonamides and identified a compound with low nanomolar potency and high selectivity (>250-fold) toward the PSEN1-APH1B subcomplex versus PSEN2 subcomplexes. We used modeling and site-directed mutagenesis to identify critical amino acids along the entry part of this inhibitor into the catalytic site of PSEN1. Specific targeting one of the different γ-secretase complexes might provide safer drugs in the future.


Gallstone ileus: Unusual complication of cholelithiasis: A case report.
Gallstone ileus is a rare cause of intestinal obstruction with a high morbidity and mortality rate, which is often linked to delayed or misdiagnosed intestinal obstruction. Gallstone ileus requires a high index of suspicion to diagnose. This report describes a 55-year-old male who presented the case of gallstone ileus with four years history of gallstone disease, emergency explorative laparotomy was done, enterotomy and stone extraction from the small bowel, the post-operative patient was uneventful and was discharged after full enteral tolerance. CT scanning has become increasingly important as a diagnostic tool, with a sensitivity of 93% and its use has increased in recent years, In the case of patients with gallstone ileus, simple enterolithotomy is both safe and effective. Gallstone Ileus is an uncommon complication of gallstone disease, most commonly seen in females in advanced age, our case report presents young adult male and high index suspicion in diagnosis and urgent intervention is mandatory for better outcome of the patients.


Nanocellulose incorporated oleogel matrix for controlled-release of active ingredients in the lower gastrointestinal tract.
Controlled release is often preferred for orally administrated bioactive compounds and drugs. In this study, a nanocellulose (NC) incorporated oleogel encapsulation system was developed for controlled release of active agents. 5-Aminosalicylic acid (5-ASA), an anti-inflammatory drug to treat inflammatory bowel diseases, was used as an example core ingredient for demonstrating the efficacy of the system. Oleogels with/without NC incorporation encapsulating 5-ASA were prepared and tested by in vitro digestion study, and 5-ASA released from the matrix was quantified by a novel UV-Vis spectrometric method developed in this study. The oleogel encapsulation system was characterized by assessing the encapsulation efficiency, oxidative stability, gel hardness, microstructure, and thermal stability. Results showed that sorbitan tristearate-induced oleogel system successfully protected 5-ASA during GI digestion. The incorporation of NC solutions with different NC types, concentrations and volumes further modified the release rate. Specifically, the release of 5-ASA in NC incorporated matrix was <6 % in the gastric phase, and ranged between 17.42 % - 38.28 % in the small intestine depending on the added NC type and concentration. Additionally, the incorporation of NC improved physicochemical stability of the gel matrix. The new 5-ASA quantification method developed in this study is simpler and faster compared with currently available methods.


Domestic dogs (Canis lupus familiaris) are sensitive to the correlation between pitch and timbre in human speech.
The perceived pitch of human voices is highly correlated with the fundamental frequency (f0) of the laryngeal source, which is determined largely by the length and mass of the vocal folds. The vocal folds are larger in adult males than in adult females, and men's voices consequently have a lower pitch than women's. The length of the supralaryngeal vocal tract (vocal-tract length; VTL) affects the resonant frequencies (formants) of speech which characterize the timbre of the voice. Men's longer vocal tracts produce lower frequency, and less dispersed, formants than women's shorter vocal tracts. Pitch and timbre combine to influence the perception of speaker characteristics such as size and age. Together, they can be used to categorize speaker sex with almost perfect accuracy. While it is known that domestic dogs can match a voice to a person of the same sex, there has been no investigation into whether dogs are sensitive to the correlation between pitch and timbre. We recorded a female voice giving three commands ('Sit', 'Lay down', 'Come here'), and manipulated the recordings to lower the fundamental frequency (thus lowering pitch), increase simulated VTL (hence affecting timbre), or both (synthesized adult male voice). Dogs responded to the original adult female and synthesized adult male voices equivalently. Their tendency to obey the commands was, however, reduced when either pitch or timbre was manipulated alone. These results suggest that dogs are sensitive to both the pitch and timbre of human voices, and that they learn about the natural covariation of these perceptual attributes.


Isolation of a C (Ibc) protein from group B Streptococcus which elicits mouse protective antibody.
The C (Ibc) proteins of group B Streptococcus (GBS) have been shown to induce mouse protective antibodies when present as immunogens on whole organisms. However, characterization of specific proteins responsible for inducing protection has not been reported. We have grown type Ic GBS in a dialysate of Todd Hewitt broth and analyzed the proteins extruded into the broth. Multiple proteins of varying size were visualized by SDS-PAGE. Ultrafiltration was used to separate the GBS components by molecular weight (MW) into 2 pools, those below 30,000 MW but above 10,000 MW (P10) and those above 30,000 MW (P30). The P10 contained 4 major proteins, including a 14,000 MW protein. Balb-c mice were immunized with the P10 fraction and the antisera used in mouse protection studies. This immune sera protected 100% of mice against challenge with type Ib GBS and protection was not altered by prior absorption of the sera with type Ia or Ib capsular polysaccharide. The P10 was fractionated by column chromatography and eluted proteins examined by SDS-PAGE and Western blot with the mouse protective antisera elicited to the P10. There was one major immunologically reactive protein at 14,000 MW which eluted in a partially purified form from the column. The 14,000 MW protein was reisolated from preparative SDS-PAGE gels and used to elicit antiserum in a rabbit. In mouse protection studies this rabbit antiserum protected mice against subsequent challenge with type Ib GBS (89% protection). Surface antigens were extracted from 125I-labelled type Ic GBS and immunoprecipitated with antiserum to the 14,000 MW protein. The 14,000 MW protein and multiple higher molecular weight proteins were immunologically cross-reactive suggesting the presence of shared epitopes. Thus the 14,000 MW protein from type Ic GBS that is antigenic and elicits mouse protective antibodies against the heterologous type Ib GBS fulfills the criteria for a C protein of GBS.


Microscopy: an art?
There can be no doubt that the finest creator of beauty is Mother Nature. And in many ways, science is the exploration of this beauty and of the mechanisms that have created it. Microscopy, as a technique in scientific investigation, has had a key role in uncovering nature's beauty, which has led some to propose that microscopy could be described as an art or even an art form. But is this claim justified?


Longer-term soy nut consumption improves vascular function and cardiometabolic risk markers in older adults: Results of a randomized, controlled cross-over trial.
Soy foods may contribute to the beneficial health effects of healthy plant-based diets on the risk to develop cardiovascular disease (CVD). However, their effects on vascular function have hardly been studied. To investigate longer-term effects of soy nut consumption on vascular function and cardiometabolic risk markers in healthy older men and women. Twenty-three healthy participants (age: 60-70 years; BMI: 20-30 kg/m2) participated in a randomized, controlled, single-blinded cross-over trial with an intervention (67 g/day of soy nuts providing 25.5 g protein and 174 mg isoflavones) and control period (no nuts) of 16 weeks, separated by eight weeks wash-out. Adults followed the Dutch food-based dietary guidelines. No serious adverse events were reported and the soy nut regime was well tolerated. Body weights remained stable during the whole study. A higher protein (3.1 energy percent [En%]) and a lower carbohydrate intake (2.0 En%) was observed during the intervention period. Total fat intake was comparable, but that of saturated (-1.3 En%), cis-monounsaturated (-1.5 En%) and cis-polyunsaturated fatty acids (+1.9 En%) differed. Serum isoflavone concentrations were higher after the intervention as compared with the control period (daidzein: 127.8 ng/mL; 95% CI: 74.3-181.3 ng/mL; p < 0.001 and genistein: 454.2 ng/mL; 95% CI: 266.6-641.8 ng/mL; p < 0.001). Brachial artery flow-mediated vasodilation was 1.48 percent points (pp; 95% CI: 0.08-2.89 pp; p = 0.040) higher following soy nut intake. The carotid artery reactivity response and arterial stiffness did not differ. Serum LDL-cholesterol was lower (0.17 mmol/L; 95% CI: 0.02-0.32 mmol/L; p = 0.027), while HDL-cholesterol and triacylglycerol concentrations were comparable. Mean arterial pressure (MAP) was lower (3 mmHg; 95% CI: 0-6 mmHg; p = 0.035). Longer-term soy nut intake as part of a healthy diet improved endothelial function, LDL-cholesterol concentrations and MAP levels, suggesting mechanisms by which an increased soy food intake beneficially affects CVD risk in older adults. Registered under ClinicalTrials.gov Identifier no. NCT03627637.


Expression of Eya1 in mouse taste buds.
Taste substances are detected by taste receptor cells in the taste buds in the oral epithelium. Individual taste receptor cells contribute to evoking one of the five taste qualities: sweet, umami, bitter, sour, and salty (sodium). They are continuously replaced every few weeks by new ones generated from local epithelial stem cells. A POU transcription factor, Pou2f3 (also known as Skn-1a), regulates the generation and differentiation of sweet, umami, and bitter cells. However, the molecular mechanisms underlying terminal differentiation into these Pou2f3-dependent taste receptor cells remain unknown. To identify the candidate molecules that regulate the differentiation of these taste receptor cells, we searched for taste receptor type-specific transcription factors using RNA-sequence data of sweet and bitter cells. No transcription factor gene showing higher expression in sweet cells than in bitter cells was found. Eyes absent 1 (Eya1) was identified as the only transcription factor gene showing higher expression in bitter cells than in sweet cells. In situ hybridization revealed that Eya1 was predominantly expressed in bitter cells and also in the putative immature/differentiating taste bud cells in circumvallate and fungiform papillae and soft palate. Eya1 is a candidate molecule that regulates the generation and differentiation of bitter cells.


Anomalous dinucleotide frequencies in both coding and non-coding regions from the genome of the human malaria parasite Plasmodium falciparum.
We have statistically analysed the distribution of nucleotides and dinucleotides in 21 genes of the 81% A + T-rich human malaria parasite Plasmodium falciparum. The mRNA-synonymous strands of this protozoan show in general a marked excess of purines over pyrimidines, correlated with abnormally high levels of Lys and Glu. We have used the large differences in base composition between coding and non-coding regions to estimate that the parasite possesses in the range of 2700-5400 genes. The dinucleotide preference patterns are compared with consensus patterns derived from other organisms [Nussinov, Nucl. Acids Res. 12 (1984) 1749-1763]. Patterns in the coding regions surprisingly resemble those of higher, rather than lower eukaryotes, particularly with respect to TG elevation and CG suppression. The latter is correlated with an abnormally low level of Arg in these parasites. In the non-coding regions, the four dinucleotides made up of C and/or G are found with significantly higher frequencies than expected (approx. 50-150%), specifically to the 5' side of the coding regions. The possible role of these dinucleotides in control sequences is discussed.