The antifungal pipeline for invasive fungal diseases: what does the future hold?
Over the last two decades, we have experienced pressing needs for new additions to the antifungal armamentarium given the emergence of resistant fungi, the growth of at-risk patient populations for invasive fungal diseases (IFD), the high morbidity and mortality associated with IFD. The current review will discuss the five promising antifungal agents for IFD (i.e. fosmanogepix, ibrexafungerp, olorofim, rezafungin, and opelconazole), now in the late-phase clinical studies, and likely to be available for clinical use in the near future. For each agent, we describe its mechanism of action, pharmacokinetic and pharmacodynamic properties, spectrum of activity as well as the safety and efficacy data, including findings from ongoing clinical trials. The potential roles of these novel antifungals in clinical practice and the key considerations for clinical use will also be discussed. There are unmet needs of these novel agents that should be addressed in the future studies. These include defining their indications and benefits, how to best target them appropriately, surveillance and stewardship of their use.


Willingness to be vaccinated against COVID-19: An exploratory online survey in a Portuguese cohort of multiple sclerosis patients.
Little is known about MS patients' acceptability of a COVID-19 vaccine. An online survey was conducted among MS patients to study COVID-19 vaccine acceptability and its associated factors. Among 256 participants, 80.9% of the patients were either definitely or probably willing to receive a COVID-19 vaccine. Most hesitant patients would consider being vaccinated under physician recommendation. Older patients and those with comorbidities seem to be more willing to get vaccinated. Moreover, vaccine acceptability was associated with participants' convictions and concerns about COVID-19, as well as previous vaccination practices.


Nx4 attenuated stress-induced activity of the anterior cingulate cortex-A post-hoc analysis of a randomized placebo-controlled crossover trial.
Stress-related symptoms are associated with significant health and economic burden. Several studies suggest Nx4 for the pharmacological management of the stress response and investigated the underlying neural processes. Here we hypothesized that Nx4 can directly affect the stress response in a predefined stress network, including the anterior cingulate cortex (ACC), which is linked to various stress-related symptoms in patients. In a randomized, placebo-controlled, double-blind, crossover trial, 39 healthy males took a single dose of placebo or Nx4. Psychosocial stress was induced by the ScanSTRESS paradigm inside an MRI scanner, and stress network activation was analyzed in brain regions defined a priori. Using the placebo data only, we could validate the activation of a distinct neural stress pattern by the ScanSTRESS paradigm. For Nx4, we provide evidence of an attenuating effect on this stress response. A statistically significant reduction in differential stress-induced activation in the right supracallosal ACC was observed for the rotation stress task of the ScanSTRESS paradigm. The results add to previously published results of Nx4 effects on emotion regulation. Our results strengthen the hypothesis that Nx4 modulates the stress response by reducing the activation in parts of the neural stress network, particularly in the ACC. NCT02602275; ClinicalTrials.gov.


Case series in drug safety: a review to determine characteristics and quality.
Case series and case reports are a cornerstone of drug safety research; however, the characteristics of case series published in the literature remain poorly examined. A narrative review of case series addressing drug safety, published in the literature between 1 January 2003 and 15 July 2009, and identified through a PubMed search, was conducted in order to determine their characteristics and quality according to the criteria found in the US FDA Pharmacovigilance Guidance 2005. Of 130 publications that met the search criteria, 11.5% included an analytical component and 88.5% were descriptive. The median number of cases included in a given case series was 7 (range 2-2195) and the median time period for recruitment of the cases was 23 months (range 0.5-96). Overall, 43.1% of case series consisted of individual case reports, while 24.6% originated from cohorts and 21% from pharmacovigilance databases. Of the case series, 65.1% concerned adults (age ≥18 years), 11.6% elderly (age ≥65 years) and 8.5% youth (<18 years). Adverse effects involved mainly the skin (18.5%) and the circulatory system (13.8%). The main suspected drug classes (Anatomical Therapeutic Chemical classification) were nervous system drugs (23.1%) and antineoplastic and immunomodulating agents (20.0%). On average, six out of the possible nine US FDA Pharmacovigilance Guidance Criteria were fulfilled, with 27% of publications fulfilling at least seven criteria. Only 10% reported data on co-morbidity. In conclusion, this review highlights the reporting gaps and heterogeneity in published case series with respect to size, recruitment period and quality.


Anterior ethmoid and frontal sinus drainage pathways: five patterns formed and defined by their bony walls.
To perform endoscopic sinus surgery safely and effectively, surgeons need to visualize the complex anatomy of the anterior ethmoid and frontal sinus region. Because this anatomy is so variable and individualized, the foundation of understanding lies in identifying, following, and visualizing the drainage pathway patterns and anticipating possible variations. We studied 100 sides (50 cases: 22 male, 28 female, aged 12-86, average age 46.5 years, ± 19.5) using computed tomography (CT) and multiplanar reconstruction (MPR) to identify and classify the drainage pathways leading to the frontal sinus and anterior ethmoidal cells. Analysis revealed five patterns of drainage pathways defined by their bony walls: between the uncinate process and the lamina papyracea [UP-LP]; between the uncinate process and the middle turbinate [UP-MT]; between the uncinate process and the accessory uncinate process [UP-UPa]; between the uncinate process and the basal lamella of the ethmoidal bulla [UP-BLEB]; and between the basal lamella of the ethmoidal bulla and the basal lamella of the middle turbinate [BLEB-BLMT]. In most cases, BLEB formed the posterior wall of the drainage pathway of the frontal sinus, indicating BLEB could be one of the most important landmarks for approaching the frontal sinus. As endoscopic sinus surgery depends on an understanding of this anatomy, this study may help surgeons to identify and follow the drainage pathways more accurately and safely through the anterior ethmoid to the frontal sinus.


Virtual Reality for Awe and Imagination.
Empirical research has explored the potential of the emotion of awe to shape creativity, while theoretical work has sought to understand the link between this emotion and transformation in terms of imagining new possible worlds. This branch of study relies on the transformative potential of virtual reality (VR) to examine and invite cognitive and emotional components of transformative experiences (TEs) within the interdisciplinary model of Transformative Experience Design (TED) and the Appraisal-Tendency Framework (ATF). TED suggests using the epistemic and emotional affordances of interactive technologies, such as VR, to invite TEs. The ATF can provide insight into the nature of these affordances and their relationship. This line of research draws on empirical evidence of the awe-creativity link to broaden the discourse and consider the potential impact of this emotion on core beliefs about the world. The combination of VR with these theoretical and design-oriented approaches may enable a new generation of potentially transformative experiences that remind people that they can aspire to more and inspire them to work toward imagining and creating a new possible world.


Ventricular systolic and diastolic impairment during pacing-induced myocardial ischemia in coronary artery disease: simultaneous hemodynamic, electrocardiographic, and radionuclide angiographic evaluation.
This study examined the impairment in systolic and diastolic performance of both ventricles during pacing-induced myocardial ischemia in 12 men with coronary artery disease. Simultaneous hemodynamic, ECG, and radionuclide angiographic assessments were made: pre pacing (pre-P); intermediate pacing (P-1); maximum pacing (P-2); and immediately after pacing (post pacing (P-P). The prepacing measurements were made with the patient in the supine position and during leg elevation. Pacing produced a leftward and upward shift in the diastolic pressure-volume relation, a progressive decrease in left ventricular (LV) end-diastolic volume (p less than 0.003) and right ventricular (RV) end-diastolic volume (p less than 0.01), concomitant with an increase in the pulmonary artery wedge pressure (p less than 0.004) and the right atrial pressure (p less than 0.04). The shift in the LV pressure-volume relation was associated with an initial increase (P-1), followed by a decrease (P-2) in the peak filling rate (p less than 0.001). Pacing also resulted in systolic dysfunction: abnormal LV ejection fraction responses in eight patients, LV regional wall motion abnormalities in eight patients, and abnormal RV ejection fraction responses in seven patients. Leg elevation resulted in a 7% increase in cardiac output, a 20% increase in RV end-diastolic volume, a 28% increase in right atrial pressure, a 29% increase in pulmonary artery wedge pressure, and a 10% increase in LV end-diastolic volume (p less than 0.05). Thus, the ischemic response to pacing results in systolic and diastolic LV and RV dysfunction, with the diastolic impairment being more frequent than the systolic impairment.


Treatment planning for peripheral arterial disease based on duplex ultrasonography and computed tomography angiography: consistency, confidence and the value of additional imaging.
Duplex ultrasonography (DUS) can be used for treatment planning for lower extremity peripheral arterial disease (PAD), but has not replaced contrast-enhanced imaging such as computed tomography angiography (CTA). We assessed DUS-based treatment planning for consistency, confidence, and the value of additional CTA among multinational surgeons. Data from 12 patients with PAD were reviewed by 2 American vascular surgeons individually and 1 Dutch vascular department by consensus. Reviewers selected treatment based on DUS first and based on added CTA second. Agreement and consistency of treatment plans was assessed using kappa statistics (κ). Imaging quality and therapeutic confidence were scored (1-5) and assessed with t-tests. Of the 36 treatment plans formulated, additional CTA confirmed 27 (75%), changed 6 (17%), and supplemented 3 (8%) plans. The approach never changed when open revascularization was selected based on DUS (14 plans; 39%). Agreement between DUS- and CTA-based treatment planning was substantial, with a mean kappa (μκ) of 0.68, but agreement between reviewers was fair (μκ DUS, 0.24; μκ CTA, 0.23). CTA received greater average scores than DUS for quality (4.36 vs 3.29; P < .0001) and confidence (4.36 vs 3.26; P < .0001). Reviewers often expressed the need for additional imaging after DUS (mean, 63%). PAD treatment planning based on CTA was mostly consistent with DUS-based treatment plans, although CTA was still felt to be needed to increase confidence. This observation suggests that to promote greater use of less invasive DUS imaging, not only improvement of DUS quality but also improvement of clinician confidence is required.


Ethanol effects on cerebellar myelination in a postnatal mouse model of fetal alcohol spectrum disorders.
Fetal alcohol spectrum disorders (FASD) are alarmingly common, result in significant personal and societal loss, and there are no effective treatments for these disorders. Cerebellar neuropathology is common in FASD and can cause impaired cognitive and motor function. The current study evaluates the effects of ethanol on oligodendrocyte-lineage cells, as well as molecules that modulate oligodendrocyte differentiation and function in the cerebellum in a postnatal mouse model of FASD. Neonatal mice were treated with ethanol from P4-P9 (postnatal day), the cerebellum was isolated at P10, and mRNAs encoding oligodendrocyte-associated molecules were quantitated by qRT-PCR. Our studies demonstrated that ethanol significantly reduced the expression of markers for multiple stages of oligodendrocyte maturation, including oligodendrocyte precursor cells, pre-myelinating oligodendrocytes, and mature myelinating oligodendrocytes. Additionally, we determined that ethanol significantly decreased the expression of molecules that play critical roles in oligodendrocyte differentiation. Interestingly, we also observed that ethanol significantly reduced the expression of myelin-associated inhibitors, which may act as a compensatory mechanism to ethanol toxicity. Furthermore, we demonstrate that ethanol alters the expression of a variety of molecules important in oligodendrocyte function and myelination. Collectively, our studies increase our understanding of specific mechanisms by which ethanol modulates myelination in the developing cerebellum, and potentially identify novel targets for FASD therapy.


Deuterium reveals the dynamics of notch activation.
Notch activation requires unfolding of a juxtamembrane negative regulatory domain (NRR). Tiyanont et al. (2011) analyzed the dynamics of NRR unfolding in the presence of EGTA. As predicted from the crystal structure and deletion analyses, the lin-Notch repeats unfold first, facilitating access by ADAM proteases. Surprisingly, the heterodimerization domain remains stable.


Effects of case-based confusion assessment methods for intensive care unit training on delirium knowledge and delirium assessment accuracy of intensive care units: A quasi-experimental study.
Delirium evaluation is important because the development of delirium in critically ill patients negatively affects their progress and prognosis. Although delirium assessment tools have been developed, nurses have insufficient experience using these tools in clinical practice. This study examined the effects of case-based confusion assessment methods for intensive care unit education on delirium knowledge and assessment accuracy for intensive care nurses. This study adopted a pre- and post-test non-equivalent control group design. The study participants were 122 general nurses (61 participants each in the experimental and control groups) working in the intensive care unit of one university hospital in South Korea. Case-based confusion assessment methods for intensive care unit education comprised lectures on delirium and confusion assessment methods for intensive care unit tools and delirium assessment education using standardized patients. The experimental group received 80-min case-based confusion assessment methods for intensive care unit training, whereas the control group received no intervention. Differences in the degree of pre- and post-knowledge in subcategories between the experimental and control groups were the cause, symptom, and management. The delirium assessment accuracy score of the experimental group changed from 2.89 ± 1.61 points before training to 8.11 ± 1.23 points after training, whereas that of the control group changed from 2.92 ± 1.94 points before training to 3.05 ± 2.99 points after training (Z = -9.668, p < .001). The case-based confusion assessment methods for intensive care unit educational program developed in this study is effective for improving delirium knowledge and delirium assessment accuracy in intensive care nurses. Based on the study results, various cases can be developed for the education of intensive care nurses.


Lecanoric acid mediates anti-proliferative effects by an M phase arrest in colon cancer cells.
Lichen extracts containing, among other compounds, depsides such as evernic acid, atranorin, and lecanoric acid possess anti-proliferative effects. We aimed to identify lichen metabolites that are responsible for the observed anti-proliferative effects. We performed cytotoxicity, cell colony, cell cycle and apoptosis assays in various cell lines or primary immune cells. We analyzed several cell cycle proteins and apoptosis-related proteins to gain insights into the underlying mechanism. All depsides reduced the viability of the tested cell lines (HCT-116, HEK293T, HeLa, NIH3T3, RAW246.7) in a cell line-dependent manner with lecanoric acid being the most effective. Atranorin did not influence the cell cycle or colony formation in HCT-116 cells, but induced apoptosis in HCT-116 cells. Evernic acid showed no anti-proliferative effects. Lecanoric acid inhibited cell colony formation already at 0.03 µg/ml in HCT-116 cells and induced a G2 cell cycle block in several cell lines. Moreover, lecanoric acid arrested the cell cycle, presumably in the M phase, since expression of cyclin B1 and phosphorylated histone H3 was upregulated, whereas the inactive cyclin-dependent kinase 1 (CDK1) was reduced in HCT-116 cells. Most importantly, cell death induced by lecanoric acid was more prominent in cancer cells than in primary human immune and endothelial cells. In conclusion, lecanoric acid seems to mediate its anti-proliferative effects via arrest of cells in the M phase. Our data suggest lecanoric acid may be a potential new candidate for anti-cancer therapy, because it has anti-proliferative effects on cancer cell lines, and does not affect primary immune cells.


Surgically induced astigmatism following single site and twin site phacotrabeculectomy augmented with mitomycin C.
To determine difference in surgically induced astigmatism (SIA), post-operative intraocular pressure (IOP) and axial length (AL) between single site and twin-site phacotrabeculectomy augmented with Mitomycin C (MMC). Prospective interventional randomised controlled study. In a prospective interventional comparative study, eligible patients were scheduled for phacotrabeculectomy. They were randomised to either group A: single site or group B: twin-site phacotrabeculectomy with MMC 0.2 mg/mL. Axial length was measured by using Zeiss IOL master I, pre-operatively and at 1, 3, 6 and 12 months post-operatively. Corneal topography was performed using Bausch and Lomb Orbscan I pre-operatively and at 3, 6 and 12 months post-operatively to analyse surgically induced astigmatism. Vector analysis was used to analyse the surgically induced astigmatism. One hundred and eight eyes of which 55 patients in group A, and 53 patients in group B were enroled for vector analysis. The mean preoperative astigmatic vector power was +0.89 ± 0.4 D and +0.97 ± 0.5 D in group A and B respectively. The mean post-operative astigmatic vector power was +0.78 ± 0.4 D in group A and +0.96 ± 0.5 D in group B at the end of 12 months. Corneal topography showed post-operative superior flattening (51.8% at 3 months and 55.4% at 12 months) in group A (P = 0.072) compared to superior steepening (59.6% at 3 months and 61.5% at 12 months) in group B (P = 0.977). The two commonly used techniques of combined cataract and glaucoma surgery proved to be efficacious without significant difference in surgical induced astigmatism.


Exploring the effect of road network, demographic, and land use characteristics on teen crash frequency using geographically weighted negative binomial regression.
Motor vehicle crashes are one of the leading causes of teen deaths worldwide. It is important to assess the environment and identify the risk factors influencing teen crashes for planning strategies and improving their safety. This research, therefore, focuses on exploring the effect of road network, demographic, and land use characteristics to compute teen crash frequency. Data for 201 spatially distributed road segments in Mecklenburg County, North Carolina, USA were considered for the evaluation. Data related to teen crashes were obtained from the Highway Safety Information System (HSIS). Demographic and land use characteristics were extracted around each selected road segment using two different buffer widths (0.25 miles and 0.5 miles). Teen crash frequency of each road segment was used as the dependent variable. The generalized linear models with the negative binomial distribution (GLM-based NB model) and geographically weighted negative binomial regression models (GWNBR and GWNBRg) were developed and compared. The annual average daily traffic (AADT), light commercial land use, number of household units, and number of pupils enrolled in public or private high schools are significant explanatory variables influencing teen crash frequency. Both methods have good predictive capabilities and can be used to compute teen crash frequency. However, the GWNBR and GWNBRg better capture the spatial dependency and spatial heterogeneity of associated risk factors influencing teen crash frequency.


An electrodiffusive, ion conserving Pinsky-Rinzel model with homeostatic mechanisms.
In most neuronal models, ion concentrations are assumed to be constant, and effects of concentration variations on ionic reversal potentials, or of ionic diffusion on electrical potentials are not accounted for. Here, we present the electrodiffusive Pinsky-Rinzel (edPR) model, which we believe is the first multicompartmental neuron model that accounts for electrodiffusive ion concentration dynamics in a way that ensures a biophysically consistent relationship between ion concentrations, electrical charge, and electrical potentials in both the intra- and extracellular space. The edPR model is an expanded version of the two-compartment Pinsky-Rinzel (PR) model of a hippocampal CA3 neuron. Unlike the PR model, the edPR model includes homeostatic mechanisms and ion-specific leakage currents, and keeps track of all ion concentrations (Na+, K+, Ca2+, and Cl-), electrical potentials, and electrical conductivities in the intra- and extracellular space. The edPR model reproduces the membrane potential dynamics of the PR model for moderate firing activity. For higher activity levels, or when homeostatic mechanisms are impaired, the homeostatic mechanisms fail in maintaining ion concentrations close to baseline, and the edPR model diverges from the PR model as it accounts for effects of concentration changes on neuronal firing. We envision that the edPR model will be useful for the field in three main ways. Firstly, as it relaxes commonly made modeling assumptions, the edPR model can be used to test the validity of these assumptions under various firing conditions, as we show here for a few selected cases. Secondly, the edPR model should supplement the PR model when simulating scenarios where ion concentrations are expected to vary over time. Thirdly, being applicable to conditions with failed homeostasis, the edPR model opens up for simulating a range of pathological conditions, such as spreading depression or epilepsy.


The A.D.A. role delineation for the field of clinical dietetics: 1. Philosophical overview and historical background.
"Role delineation" involves identifying responsibilities and supporting skill and knowledge components which must be demonstrated by practitioners as they deliver quality services. As part of its efforts to meet demands for competent clinical dietetic practitioners, the American Dietetic Association conducted a role delineation study for entry-level clinical dietetic personnel. A.D.A.'s efforts in role delineation are situated in the history and future needs of the profession. This investigation was federally funded to identify the "actual" and "appropriate" role responsibilities and supporting skills and knowledge for clinical dietetic personnel. A series of assumptions delimit the conditions underlying role performance. To address the needs of A.D.A. members and organizational entities, immediate use of the A.D.A.-endorsed study products is planned.


Guyon Canal Syndrome Due to Schwannomas of Zone 3 Ulnar Nerve without Neurologic Symptoms: A Case Report.
We report a mass without neurologic findings and moderate pain in a 33-year-old male's wrist at the 3rd zone of the ulnar nerve due to schwannoma that was excised successfully, and the patient was free of symptoms. We further discuss the prevalence and management of this lesion.


Preoperative MRI-Based Radiomics of Brain Metastasis to Assess T790M Resistance Mutation After EGFR-TKI Treatment in NSCLC.
Preoperative assessment of the acquired resistance T790M mutation in patients with metastatic non-small cell lung cancer (NSCLC) based on brain metastasis (BM) is important for early treatment decisions. To investigate preoperative magnetic resonance imaging (MRI)-based radiomics for assessing T790M resistance mutation after epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment in NSCLC patients with BM. Retrospective. One hundred and ten primary NSCLC patients with pathologically confirmed BM and T790M mutation status assessment from two centers divided into primary training (N = 53), internal validation (N = 27), and external validation (N = 30) sets. Contrast-enhanced T1-weighted (T1CE) and T2-weighted (T2W) fast spin echo sequences at 3.0 T. Forty-five (40.9%) patients were T790M-positive and 65 (59.1%) patients were T790M-negative. The tumor active area (TAA) and peritumoral edema area (POA) of BM were delineated on pre-treatment T1CE and T2W images. Radiomics signatures were built based on features selected from TAA (RS-TAA), POA (RS-POA), and their combination (RS-Com) to assess the T790M resistance mutation after EGFR-TKI treatment. Receiver operating characteristic (ROC) curves were used to assess the capabilities of the developed RSs. The area under the ROC curves (AUC), sensitivity, and specificity were generated as comparison metrics. We identified two features (from TAA) and three features (from POA) that are highly associated with the T790M mutation status. The developed RS-TAA, RS-POA, and RS-Com showed good performance, with AUCs of 0.807, 0.807, and 0.864 in the internal validation, and 0.783, 0.814, and 0.860 in the external validation sets, respectively. Pretreatment brain MRI of NSCLC patients with BM might effectively detect the T790M resistance mutation, with both TAA and POA having important values. The multi-region combined radiomics signature may have potential to be a new biomarker for assessing T790M mutation. 3 TECHNICAL EFFICACY: Stage 2.


Introducing an Integrated Model of Adults' Wearable Activity Tracker Use and Obesity Information-Seeking Behaviors From a National Quota Sample Survey.
Research from multiple perspectives to investigate adults' use of wearable activity-tracking devices is limited. We offer a multiperspective model and provide empirical evidence of what leads to frequent usage of wearable health technologies from a large, nationally representative survey sample. This study aims to explore factors affecting the use of wearable activity-tracking devices among health consumers from the perspectives of individual health beliefs (perceived severity, perceived susceptibility, perceived benefits, and self-efficacy) and information-seeking behaviors. Our Integrated Model of Wearable Activity Tracker (IMWAT) use and proposed hypotheses were validated and tested with data collected from a telephone survey with a national quota sample. The data were analyzed using a variety of statistical techniques, including structural equation analysis. The sample comprised 2006 participants. Our results showed that the perceived benefits of physical activity, perceived susceptibility, and self-efficacy toward obesity were significant predictors of information-seeking behaviors, which, in turn, mediated their effects on the use of wearable activity trackers. Perceptions of obesity severity directly promoted wearable device usage. This study provided a new and powerful theoretical model that combined the health beliefs and information-seeking behaviors behind the use of wearable activity trackers in the adult population. The findings provide meaningful implications for developers and designers of wearable health technology products and will assist health informatics practitioners and obesity prevention communicators.


Vaccine development for the prevention of staphylococcal mastitis in dairy cows.
Staphylococci are the most common and costly mammary disease of dairy cattle worldwide. Target of RNAIII Activating Protein (TRAP), a membrane associated 167AA protein, is highly conserved among staphylococci and was shown in Staphylococcus aureus to be involved in bacterial stress response. The aims of this study were to test the safety and efficacy of recombinant TRAP (rTRAP) vaccine in dairy animals. The vaccine was safe as 2-3 subcutaneous injections of rTRAP (54-100 μg) with adjuvant ISA 206 to cows and goats did not lead to any abnormal symptoms of sensitivity to the vaccine. The rTRAP vaccine was immunogenic and caused the induction of a humoral immune response that remained high for at least 160 d post second immunization. The rTRAP vaccine was efficacious; at parturition only 13.5% (5/37) heifers in the immunized group were infected with Staphylococcus chromogenes as compared to 42.9% (18/42) in the non-immunized group. Additionally, when cows were immunized in mid-lactation, the difference between somatic cell count (SCC) in immunized and control animals was profound (45 ± 7 vs. 470 ± 194, respectively). At the same time, the difference in milk yield was also evident (48.3 ± 1.4 L d(-1)vs. 44.3 ± 0.9 L d(-1), respectively). Put together, these studies indicate the value of the rTRAP vaccine in preventing new udder infections by staphylococci, which significantly lead to lowered SCC and some increase in milk yield. TRAP is conserved among all strains and species and is constitutively expressed in any strain of S. aureus or CNS tested so far, including those isolated from cows. TRAP may thus serve as a universal anti-staphylococcus vaccine.


Neuropeptide diuretic hormone 31 mediates memory and sleep via distinct neural pathways in Drosophila.
Memory formation and sleep regulation are critical for brain functions in animals from invertebrates to humans. Neuropeptides play a pivotal role in regulating physiological behaviors, including memory formation and sleep. However, the detailed mechanisms by which neuropeptides regulate these physiological behaviors remains unclear. Herein, we report that neuropeptide diuretic hormone 31 (DH31) positively regulates memory formation and sleep in Drosophila melanogaster. The expression of DH31 in the dorsal and ventral fan-shaped body (dFB and vFB) neurons of the central complex and ventral lateral clock neurons (LNvs) in the brain was responsive to sleep regulation. In addition, the expression of membrane-tethered DH31 in dFB neurons rescued sleep defects in Dh31 mutants, suggesting that DH31 secreted from dFB, vFB, and LNvs acts on the DH31 receptor in the dFB to regulate sleep partly in an autoregulatory feedback loop. Moreover, the expression of DH31 in octopaminergic neurons, but not in the dFB neurons, is involved in forming intermediate-term memory. Our results suggest that DH31 regulates memory formation and sleep through distinct neural pathways.


Monitoring the prenatal detection of structural fetal congenital anomalies in England and Wales: register-based study.
To provide current population-based prevalence and prenatal diagnosis rates (PND) for specified major congenital anomalies in England and Wales to enable monitoring of the Fetal Anomaly Screening Programme (FASP). Secondary analysis of prospectively collected registry data. Seven multiple-source, population-based congenital anomaly registers, members of the British Isles Network of Congenital Anomaly Registers (BINOCAR) in 2005 and 2006. 2,883 births with congenital anomalies from a total of 601,545 live and stillbirths. PND and birth prevalence of selected congenital anomaly groups/subtypes (anencephaly, spina-bifida, serious cardiac, diaphragmatic hernia, gastroschisis, exomphalos, bilateral renal agenesis, lethal/severe skeletal dysplasia, cleft lip with or without cleft palate [CL + /- P]). Of the selected anomaly groups, the most frequently reported were serious cardiac (14.1 per 10,000 births [95% CI 13.0-15.2]) and CL + /- P (9.7 per 10,000 births [8.9-10.5]); the least frequent were bilateral renal agenesis and lethal/severe skeletal dysplasia (< 1.5 per 10,000 births). The PND varied for different anomalies from 53.1% (95% CI 43.5-65.2) for serious cardiac anomalies to 99.6% (95% CI 97.9-100.0) for anencephaly. Least variation in PND rates was for anencephaly (range 98.9-100%) and gastroschisis (93.5-100%); greatest variation was for serious cardiac (43.5-65.2%) and lethal/severe skeletal dysplasias (50.0-100%). BINOCAR registers can, uniquely, provide contemporary data on PND and birth prevalence rates to enable monitoring of the ultrasound component of FASP at a national and regional level, allowing comparisons between populations to be made, planning of resources facilitated and assistance for parents making informed decisions on whether to enter the screening programme.


Prediction of acetaminophen level from clinical history of overdose using a pharmacokinetic model.
A retrospective study was undertaken to determine the accuracy of predicting acetaminophen levels using the pharmacokinetic equation for first-order absorption and elimination of a single oral ingestion, (Formula: see text) Forty-four acute adult acetaminophen overdoses were studied during a 22-month period. Eighty levels drawn from 0 to 16 hours after ingestion were evaluated. To standardize the data, only first levels drawn in patients without prior spontaneous or ipecac-induced vomiting were analyzed (n = 26). Of these 26 levels, eight (31%) were drawn from 0 to two hours after ingestion, eight (31%) from two to four hours, and ten (38%) from four to 16 hours, with correlations of 0.59, 0.85, and 0.98, respectively. To determine the accuracy of predicting four-hour levels, five patients with first levels drawn at four hours, prior to vomiting, were evaluated. Substituting appropriate constants, the condensed equation, Cp4h = (0.59) (mg/kg dose), was used to predict the four-hour level (r = 0.99). Preliminary data suggest the ability to accurately predict four-hour acetaminophen levels from ingestion history alone using pharmacokinetic equations.


Molecular and functional characterization of P-glycoprotein in vitro.
The blood-brain barrier (BBB) physically and metabolically functions as a neurovascular interface between the brain parenchyma and the systemic circulation, and regulates the permeability of several endogenous substrates and xenobiotics in and out of the central nervous system. Several membrane-associated transport proteins, such as P-glycoprotein (P-gp), multidrug resistance-associated proteins, breast cancer resistance protein, and organic anion transporting polypeptides, have been characterized at the BBB and identified to play a major role in regulating the brain bioavailability of several pharmacological agents. This chapter reviews several well-established techniques for the study of the molecular expression, cellular localization, and functional activity of transport proteins in primary and immortalized cell culture systems of the BBB. In particular, we describe the molecular characterization of P-gp/MDR1 at the transcript level using semiquantitative polymerase chain reaction (PCR), at the protein level using immunoblotting, and at the cellular level using immunofluorescence. In addition, the uptake/efflux and transepithelial flux studies, which characterize P-gp transport activity, are described.


Analysis of the error in measurement of ultrasound speed in tissue due to waveform deformation by frequency-dependent attenuation.
A systematic error exists in measurement of ultrasound speed in tissue with pulse methods. Frequency-dependent attenuation distorts the incident waveform as it passes through tissue causing an error in determination of speed when the time interval between fixed points on the incident and transmitted waveforms is measured. Two equations have been derived for a generalized pulse in a non-dispersive medium that enable calculation of this error when the peaks of the waveforms or the zero-crossings are used as reference points in the speed measurement. The errors have been calculated for measurement of speed in muscle, liver and fat for path lengths of 5, 10, an 15 cm for two incident pulse shapes. In general, the magnitude of this error is small compared to the biological variation, but may be significant compared to experimental error.


Comparison of a new tumour marker CA 242 with CA 19-9, CA 50 and carcinoembryonic antigen (CEA) in digestive tract diseases.
The levels of CA 242, a new tumour marker of carbohydrate nature, were measured in sera of 185 patients with malignancies of the digestive tract and of 123 patients with benign digestive tract diseases. High percentages of elevated CA 242 levels (greater than 20 U ml-1) were recorded in patients with pancreatic and biliary cancers (68%). The sensitivity was somewhat lower than that of CA 19-9 (76%) and CA 50 (73%). On the other hand, in benign pancreatic and biliary tract diseases the CA 242 level was less frequently elevated than the CA 19-9 and CA 50 levels. The serum CA 242 concentration was increased in 55% of patients with colorectal cancer. CA 242 detected more Dukes A-B carcinomas (47%) than CEA (32%), whereas CEA was more often elevated (71% vs 59%) in Dukes C-D carcinomas. CA 242 was slightly elevated (ad 41 U ml-1) in 10% of patients with benign colorectal diseases. CA 50 and CA 19-9 had lower sensitivities than CA 242 using the recommended cut-off values. When cut-off levels based on relevant benign colorectal diseases were used, the sensitivities of these markers were similar and somewhat higher than that of CEA. Less than half of patients with gastric cancer (44%) had an elevated CA 242 serum level. CA 242 is a promising new tumour marker, that may be of additional value in the diagnosis of pancreatic and biliary, as well as colorectal cancer, and may be useful in monitoring cancer patients after radical surgery.


Cephalosporin resistance, tolerance, and approaches to improve their activities.
Cephalosporins comprise a β-lactam antibiotic class whose first members were discovered in 1945 from the fungus Cephalosporium acremonium. Their clinical use for Gram-negative bacterial infections is widespread due to their ability to traverse outer membranes through porins to gain access to the periplasm and disrupt peptidoglycan synthesis. More recent members of the cephalosporin class are administered as last resort treatments for complicated urinary tract infections, MRSA, and other multi-drug resistant pathogens, such as Neisseria gonorrhoeae. Unfortunately, there has been a global increase in cephalosporin-resistant strains, heteroresistance to this drug class has been a topic of increasing concern, and tolerance and persistence are recognized as potential causes of cephalosporin treatment failure. In this review, we summarize the cephalosporin antibiotic class from discovery to their mechanisms of action, and discuss the causes of cephalosporin treatment failure, which include resistance, tolerance, and phenomena when those qualities are exhibited by only small subpopulations of bacterial cultures (heteroresistance and persistence). Further, we discuss how recent efforts with cephalosporin conjugates and combination treatments aim to reinvigorate this antibiotic class.


3D printed colloidal biomaterials based on photo-reactive gelatin nanoparticles.
Biomaterials-based strategies have shown great promise for tissue regeneration. 3D printing technologies can deliver unprecedented control over architecture and properties of biomaterial constructs when combined with innovative material design strategies. Colloidal gels made of polymeric nanoparticles are attractive injectable and self-healing systems, but their use as bio-inks for extrusion-based printing is largely unexplored. Here, we report 3D printing of novel biomaterial constructs with shape memory behavior using photo-reactive gelatin nanoparticles as colloidal building blocks. These nanoparticles are stabilized with intraparticle covalent crosslinks, and also contain pendant methacryloyl groups as photo-reactive moieties. While non-covalent interactions between nanoparticles enable formation of colloidal gel inks that are printable at room temperature, UV-induced covalent interparticle crosslinks based on methacryloyl moieties significantly enhance mechanical properties of printed constructs. Additionally, the UV crosslinking modality enables remarkable control over swelling, degradation, and biomolecule release behavior of 3D constructs. Finally, by exploiting the mechanical properties of colloidal biomaterials after UV crosslinking, 3D constructs can be designed with shape memory properties, returning to their original programmed geometry upon re-hydration. Accordingly, these novel colloidal inks exhibit great potential to serve as bio-inks for 3D printing of biomaterials with shape-morphing features for a wide range of tissue engineering and regenerative medicine applications.


Vocal fold paralysis in infants twelve months of age and younger.
Seventeen cases of unilateral or bilateral vocal fold paralysis were diagnosed in infants younger than 12 months from 1991 to 1994 at the University of Iowa Hospitals and Clinics. Eight (47%) children with left vocal fold paralysis had a history of prior thoracic surgery--two to repair complex congenital anomalies and six to ligate a patent ductus arteriosus. During the study period, a total of 81 patent ductus arteriosus ligations were performed, yielding a 7.4% postoperative incidence of vocal fold paralysis. Seven (41%) children had idiopathic vocal fold paralysis (3 right, 1 left, 3 bilateral). Two (12%) children had VFP caused by central nervous system pathology (1 right, 1 bilateral). Tracheotomy was not required in any case. Prognosis for vocal fold paralysis varied with cause. With left vocal fold paralysis caused by thoracic surgery, no improvement was noted after an average follow-up of 6 months; with idiopathic vocal fold paralysis infants improved within an average of 6 weeks of diagnosis; with vocal fold paralysis caused by central nervous system pathology, treatment of the underlying condition was followed by return of vocal cord function. Irrespective of cause, the morbidity associated with vocal fold paralysis is minimal. Although tracheotomy is not required, careful airway observation is important. Differences and similarities of these results with other studies are discussed.


Enterobius vermicularis and risk factors in healthy Norwegian children.
The prevalence of Enterobius vermicularis in neighboring countries of Norway show large variation. The goal of this study was to investigate the prevalence among Norwegian children and possible risk factors. The children were participants in "Environmental Triggers of Type 1 Diabetes: the MIDIA study." The study involved 2 groups with different genetic risks of type 1 diabetes: A high-risk group carries the Human Leukocyte Antigen genotype conferring the highest risk for type 1 diabetes and a nonhigh-risk group consisting of children without this genotype. Scotch tape samples were collected on 3 consecutive days and examined by light microscopy. A total of 18% (72/395) of children were positive for E. vermicularis. The highest prevalence (34%) was in children 6-11 years of age. Only 2 children were prior known positives. Increased number of siblings was linked to more infections, and there were fewer infections in the children with the high-risk genotype. E. vermicularis is a common parasite in Norwegian children. The likelihood of E. vermicularis infection depends on family size and prevalence increases with age. The reduced number of infections in the children carrying the high-risk genotype for type 1 diabetes is intriguing and should be investigated further.


Prediction of pathological complete response in breast cancer patients during neoadjuvant chemotherapy: Is shear wave elastography a useful tool in clinical routine?
To compare the validity of Shear Wave Elastography (SWE) for the preoperative assessment of pathological complete response (pCR) to standard clinical assessment in breast cancer patients undergoing neoadjuvant chemotherapy (NACT). This prospective, consecutive clinical trial was conducted under routine clinical practice. Analysis included 134 patients. SWE served as index test, final pathology from surgical specimen as reference standard. PCR (ypT0) was defined as primary endpoint. Elasticity changes were compared for the pCR- vs. non-pCR group. To determine the validity of shear wave velocity (Vs), ROC analyses and diagnostic accuracy parameters were calculated and compared to the final standard clinical assessment by physical examination, mammography and B-mode ultrasound (ycT + vs. ycT0). Vs was significantly reduced in pCR and non-pCR groups during NACT (pCR: ΔVs(abs) = 3.90 m/s, p < 0.001; non-pCR: ΔVs(abs) = 3.10 m/s, p < 0.001). The pCR-group showed significant lower Vs for all control visits (t1,2,END: p < 0.001). ROC analysis of Vs yielded moderate AUCs for the total population (t0: 0.613, t1: 0.745, t2: 0.685, tEND: 0.718). Compared to standard clinical assessment, Vs(tEND) (cut-off: ≤3.35 m/s) was superior in sensitivity (79.6 % vs. 54.5 %), NPV (86.4 % vs. 77.5 %), FNR (20.4 % vs. 45.5 %), inferior in specificity (58.6 % vs. 77.5 %), PPV (46.3 % vs. 54.5 %), FPR (41.4 % vs. 22.5 %). SWE measures significant differences in tumour elasticity changes in pCR vs. non-pCR cases. SWE shows improved sensitivity compared to standard clinical assessment, high NPV and low FNR, but failed in specificity in order to predict pCR under routine conditions.


Nigeria's scientific contributions to COVID-19: A bibliometric analysis.
The COVID-19 pandemic has prompted a historic global research effort to create a knowledge base that can guide mitigation strategies. This study uses the Scopus database to examine the literature published by Nigerian institutions since the outbreak of COVID-19, with a focus on bibliometric items, global collaboration, Scopus subject area classification, document types, active authors and institutions, journals, highly cited papers, and funding agencies. We searched for articles indexed in the Scopus database between January 1st, 2020 and July 20th, 2022 using predetermined search terms. All article types and study designs were included. During the period under consideration, researchers affiliated with Nigerian institutions published a total of 2,217 COVID-19 papers out of a total of 281,589 global outputs, implying that Nigerian institutions contributed 0.8% of total global COVID-19 scientific output. The majority of the documents published were articles/original research (n = 1,455, 68.4%). The National Institute of Health was the top funder, and the University of Ibadan was the most active institution. The vast majority of publications (38.3%) were in the field of health sciences, with 1197 papers in the medicine sub-category. The top journal was Pan African Medical Journal, which published 114 COVID-19 papers with at least one Nigerian institution affiliation. The most active collaborator with Nigerian institutions was the United States. With 745 citations, the most cited paper with at least one Nigerian institution affiliation was from the Nigeria Center for Disease Control. Nigerian institutions have contributed to the scientific output of COVID-19. There is, however, a need to improve research capacity across all subject areas.


Situational influences on response time and maneuver choice: Development of time-critical scenarios.
Findings concerning drivers' response times to sudden events vary considerably across studies due to different experimental setups and situational characteristics, such as expectancy of an event and urgency to react. While response times are widely reported in the literature, understanding of drivers' choice of maneuvers in time-critical situations is limited. Standardized test scenarios could enhance the comparability of studies and help in attaining a better understanding of driver behavior in these situations. In an effort to achieve these improvements, three driving simulator studies (N = 131) were conducted to investigate drivers' response time and maneuver choice under a range of situational conditions. Each study took place in a specific environmental setting (urban, rural, and highway) and incorporated one unexpected and 12 subsequent events (increased expectancy). Four different time-critical scenarios were used to evoke different driver responses. In three scenarios, obstacles suddenly entered the roadway (braking, steering, or both possible). A fourth scenario comprised the sudden braking of a leading vehicle (only braking possible). Half of the drivers performed a cognitive secondary task. To validate the findings, results from an additional field test (N = 14) were compared to the results from the simulated urban environment. As expected, response choice was influenced by scenario characteristics (available braking distance and room for evasive maneuvers). Braking maneuvers were more frequent in settings with lower speed limits (urban) while steering maneuvers were found at higher speed limits (highway). Responses to suddenly appearing obstacles were fastest in the urban setting at 540-680 ms; these responses were 200-300 ms slower in the rural and highway settings. Response times increased by 100-200 ms when drivers responded to braking leading vehicles rather than obstacles. Braking responses were 200-350 ms slower and steering responses were 90-200 ms slower when drivers responded to an unexpected event rather than subsequent events. The cognitive secondary task had no significant effect. The simulated environment and the field test produced comparable response behavior. The current study provides reference numbers that help to establish a set of standardized test scenarios for future studies. On basis of this study, nine scenarios are recommended for the context of time-critical crash avoidance maneuvers. Such standardized test scenarios could improve the comparability of future studies on response time and maneuver choice.


Development of a cholesterol-conjugated fluorescent sensor for site-specific detection of zinc ion at the plasma membrane.
A cholesterol-conjugated fluorescence Zn(2+) sensor based on the fluorescein platform was designed and synthesized. The cholesterol moiety is essential for localizing the Zn(2+) sensor to the cell membrane, allowing the sensor to probe changes in the Zn(2+) concentration in a localized area of the cell.


A prospective, randomized study to evaluate the efficacy of various diuretic strategies in acute decompensated heart failure.
To evaluate the safety and efficacy of various initial strategies of loop diuretic administration in patients with acute decompensated heart failure (ADHF) on diuresis, renal function, electrolyte balance and clinical outcomes. Consecutive patients admitted with ADHF were randomized into three groups - intravenous furosemide infusion + intravenous dopamine, intravenous furosemide bolus in two divided doses and intravenous furosemide continuous infusion alone. At 48 h, the treating physician could adjust the diuretic strategy. Primary endpoint was negative fluid balance at 24 h after admission. Secondary end points were duration of hospital stay, negative fluid balance at 48, 72, 96 h, the trend of serum electrolytes, and renal function and 30 day clinical outcome (death and emergency department visits). Overall ninety patients (thirty in each group) were included in the study. There was a greater diuresis in first 24 h (p = 0.002) and a shorter hospital stay (p = 0.023) with the bolus group. There was no significant difference in renal function and serum sodium and serum potassium levels. There was no difference in the number of emergency department visits among the three groups. All three modes of diuretic therapies can be practiced with no difference in worsening of renal function and electrolyte levels. Bolus dose administration with its rapid volume loss and shorter hospital stay might be a more effective diuretic strategy.


Knowledge and attitude about cervical cancer and human papillomavirus vaccine among medical and paramedical students of a university.
Every year, globally 570,000 women are diagnosed with cervical cancer, out of which around 311,000 die. India contributes to about 132,000 new cases and 74,000 deaths yearly. One of the major risk factors for cervical cancer is infection with some types of human papillomavirus (HPV). This is both preventable (by vaccination) and detectable early (routine screening programs). The objective of this study is to assess the knowledge and attitude in medical and paramedical students about cervical cancer and HPV vaccination. A cross-sectional survey was conducted, using predesigned and validated questionnaire. It was segregated into three parts: Q1-demographic details, Q2a-questions assessing knowledge, Q2b-questions assessing attitude. Our target population was female students (18-25 years) studying in medical, nursing, and physiotherapy colleges. Descriptive statistics of data was analyzed using SPSS 16.0. We had 73% response rate. Most participants belonged to upper middle and upper socioeconomic class, were pursuing MBBS, resided in villages, had educated parents, and had good health-care-seeking behavior. School education, television, and printed advertisements appeared to be underutilized. Around 50% of the participant had received chickenpox and typhoid vaccine, but only 8% had received HPV vaccine. The mean knowledge score was 5.19 ± 2.24, with 0.00 minimum and 11.0 maximum, out of a maximum possible score of 17. Only, place of residence appeared to effect the knowledge score. The study shows the dismal knowledge levels about HPV amongst students. Participants were interested in seeking knowledge; consider HPV vaccination provided they were provided with sufficient knowledge.


Identification of QTLs in oil palm (Elaeis guineensis Jacq.) using SSR markers through association mapping.
Oil palm (Elaeis guineensis Jacq.) is a perennial vegetable and a high oil-yielding crop (4-6 t/ha). There is a large scope for increasing the oil yield by selecting elite planting material for breeding programme in germplasm evaluation, characterization and utilization. In the present study, a diverse range of 150 oil palm genotypes were characterized using 12 quantitative variables with 54genomic microsatellite markers. A wide variation was observed in the morphological traits among indigenous populations. Highly significantand positive correlations were observed between vegetative dry matter (VDM) and total dry matter (TDM) (0.862), and height and height increment (0.838). The first two principal component analyses explained 67.7% of total variation among morphological traits. The genotypes IC0610001-59 (Pune-2) and IC0610001-60 (Pune-2) were found highly promising based on less height increment, more TDMwith high yield. For the mapping study, general linear model (GLM) approach, quantitative-trait loci (QTL) for annual height increment, number of bunches, bunch yield and bunch index were linked to simple-sequence repeat (SSR) loci mEgCIR3649 with phenotypic variance of 15.08, 10.43, 11.74, 15.39. TDM and VDM were linked to mEgCIR0192 (27.34 and 24.19%), mEgCIR3684 (16.84 and 18.30%), SPSC00163 (18.8 and 15.39%) and mEgCIR0555 (16.47 and 18.81%), with at a significant threshold (P) level of B0.001 and by mixed linear model (MLM) approach. TDM was linked to mEgCIR0555 with phenotypic variance of 20.72%, bunch yield and bunch index were linked to mEgCIR2813 at phenotypic variance of 17.11% and 12.88%, respectively, at a significant threshold (P) level of B0.01.


The toxicity of composts from sewage sludges evaluated by the direct contact tests phytotoxkit and ostracodtoxkit.
Limitations relating to permissible standards of undesirable substances in sewage sludges make it necessary to optimize sludge properties. One of the methods to achieve the above goal is the use of a composting process. The aim of this study was to determine the toxicity of composts obtained from sewage sludges composted for 76 days. Dewatered sewage sludges were collected from the four wastewater treatment plants located in the south-eastern part of Poland (Kraśnik, Lublin, Biłgoraj and Zamość). The sludges were mixed with standard OECD soil at doses of 6% and 24%. Phytotoxkit (with Lepidium sativum) and ostracodtoxkit (with Heterocypris incongruens) tests were used to evaluate toxicity. The results obtained showed different toxicity of sewage sludge depending on the sludge dose and bioassay used. H. incongruens mortality ranged from 0% to 90% and depended on the sewage sludge. The greatest inhibition of test organism growth was noted at a level of 55%. In the case of the Phytotoxkit test, a clearly negative influence of the sewage sludges on seed germination was observed at a dose of 24%. Root growth inhibition was noted in the case of most sewage sludges and was at a level of 20-100%. The influence of the composting on the toxicity of biosolids also showed various trends depending on the sludge type. Sludge composting often resulted in a toxicity increase in relation to H. incongruens. In the case of plants (Phytotoxkit test) and most sewage sludges, however, the composting process influenced both the seed germination and root growth in a positive way.


Mesophyll conductance exerts a significant limitation on photosynthesis during light induction.
Past studies have established mesophyll diffusion conductance to CO2 (gm ) as a variable and significant limitation to plant photosynthesis under steady-state conditions. However, the role of gm in influencing photosynthesis (A) during the transient period of light induction is largely unknown. We combined gas exchange measurements with laser-enabled carbon isotope discrimination measurements to assess gm during photosynthetic induction, using Arabidopsis as the measurement species. Our measurements revealed three key findings: (1) we found that the rate at which gm approached steady state during induction was not necessarily faster than the induction rate of the carboxylation process, contradictory to what has been suggested in previous studies; (2) gm displayed a strong and consistent coordination with A under both induction and steady-state settings, hinting that the mechanism driving gm -A coupling does not require physiological stability as a prerequisite; and (3) photosynthetic limitation analysis of our data revealed that when integrated over the entire induction period, the relative limitation of A imposed by gm can be as high as > 35%. The present study provides the first demonstration of the important role of gm in limiting CO2 assimilation during photosynthetic induction, thereby pointing to a need for more research attention to be devoted to gm in future induction studies.


Aberrations of chromosome 8 in mixed salivary gland tumors--cytogenetic findings on seven cases.
Cytogenetic findings on seven mixed salivary gland tumors are reported herein. The involvement of chromosome #8 in clonal chromosome aberrations in five of the seven tumors was particularly noteworthy. Four tumors had translocations involving chromosome #8 and one or two other chromosomes (#3, #7, #9, #13). The fifth showed a deletion of parts of the long arm of chromosome #8. In an attempt to define the critical segment on chromosome #8, we have identified the part between 8q11 and 8q13 as the critical region involved in all rearrangements. Thus far, our results confirm the results of the Swedish group, though the percentage of cases having #8 abnormalities is somewhat higher in our small series. The relationship between the two groups of cases, those with and those without chromosome abnormalities, will be discussed.


Pudendal nerve function in women with symptomatic utero-vaginal prolapse.
Pelvic floor function has been studied in 27 women with symptomatic utero-vaginal prolapse and 15 age-matched control subjects. There was no evidence in the patients on physiological testing of significant denervation of the pelvic floor muscles, with no significant difference in the maximum resting and squeeze anal pressures, the pudendal nerve terminal motor latency or external anal sphincter fibre density on single fibre electromyography between the groups. However, those patients with a small rectocele (less than 2 cm) had a significantly higher fibre density than the group with a large rectocele (p = 0.03) and the control group (p less than 0.001). Six of eight patients with a small rectocele had increased fibre density compared with 3/19 with a large rectocele (p = 0.006) and 2/15 control subjects (p = 0.006). This was independent of age, obstetric factors and the presence of internal rectal prolapse. These findings suggest that patients with symptomatic utero-vaginal prolapse and small rectoceles have pelvic nerve damage, and development of a large rectocele may provide some protection against perineal descent and pudendal neuropathy, although the number of patients in the small rectocele group was small and confirmation from further similar studies is required.


Process Analytical Technologies - Advances in bioprocess integration and future perspectives.
Process Analytical Technology (PAT) instruments include analyzers capable of measuring physical and chemical process parameters and key attributes with the goal of optimizing process controls. PAT in the form of a probe or sensor is designed to integrate within the pharmaceutical manufacturing line and is coupled with computing equipment to perform chemometric modeling for result interpretation and multilayer statistical control of processes. PAT solutions are intended for understanding bioprocesses with a goal to control quality at all stages of product manufacturing and achieve quality by design (QbD). The goal of PAT implementation is to promote real-time release of products to decrease the cycle time and cost of production. This review focuses on the applications of PAT solutions at different stages of the manufacturing process for vaccine production, the advantages, challenges at present state, and the vision of the future development of biopharmaceutical industries.


X-ray absorption spectroscopy and X-ray diffraction data for molybdenum minerals and compounds.
We report Mo K- and LIII-edge X-ray absorption spectroscopy (XAS) and X-ray diffraction (XRD) data collected for 15 molybdenum minerals and compounds sourced from museum collections, mineral dealers, and chemical suppliers. The samples were finely ground and analyzed at the Canadian Light Source synchrotron (Saskatoon, Canada). The LIII-edge XAS data were collected in fluorescence and total electron yield mode, while the K-edge XAS data were collected in transmission and fluorescence modes. Molybdenum LIII-edge spectra cover the X-ray absorption near edge structure (XANES) region and Mo K-edge spectra cover the extended X-ray absorption fine structure (EXAFS) region. Tabulated XAS data are provided to support analysis of XAS data obtained for geological or environmental research. Furthermore, Mo K-edge EXAFS and LIII-edge XANES spectra, the k3 weighted oscillatory χ(k) functions, and the Fourier-transforms in χ(R) of these K-edge data are presented graphically. Corresponding XRD data were collected as two-dimensional images against an area detector and integrated to form line scans. The data were collected at a wavelength of 0.68866 Å (18 keV) and is tabulated and presented graphically over a 0-40 °2Θ range. This dataset is intended to be used as reference material for a variety of rare and common Mo phases.


Fasciola hepatica: tegumental changes induced in vitro by the deacetylated (amine) metabolite of diamphenethide.
The effect of the deacetylated (amine) metabolite of diamphenethide (10 mugm/ml) on the tegument of Fasciola hepatica over a 24 hr period in vitro has been determined by means of transmission electron microscopy. In the tegumental syncytium, there is an initial accumulation of T2 secretory bodies at the apical surface (after 6 hr), together with increased exocytosis of secretory bodies and blebbing of the surface membrane. After 9 hr, the two surfaces of the fluke show different tegumental responses to drug treatment with a marked swelling of the basal infolds in the dorsal tegument, while the ventral tegument remains normal. By 18 hr, the swelling in the dorsal tegument is very severe, the entire basal region becoming edematous. In some areas, the tegument becomes detached to expose the basal lamina. The ventral tegument retains a fairly normal morphology, although there is a slight swelling of the basal infolds. The edema spreads internally to the cell bodies, beginning after 9 hr on the dorsal side of the fluke and 18 hr on the ventral side. By 18 hr, the flooding on the dorsal side is very severe and the cells attenuated, retaining few contacts with the surrounding parenchyma. From 9 hr onwards, there are progressive changes in cell structure, including a decrease in amount of granular endoplasmic reticulum and extent of its ribosomal covering, a decrease in numbers of secretory bodies, a swelling of the trans-most Golgi cisternae and disruption of the release of secretory bodies, and a swelling and disorganization of the mitochondria. The results are discussed in relation to the postulated activity of the deacetylated (amine) metabolite of diamphenethide as a Na+ ionophore.


The Relationship Between COVID-19 Confinement, Psychological Adjustment, and Sexual Functioning, in a Sample of Portuguese Men and Women.
Past research has revealed the detrimental effects of social isolation and physical distancing measures in health related outcomes. However, only recently COVID-19 confinement measures provided a context to test whether such detrimental effects exist in the human sexuality domain. This study was aimed at testing the relationship between COVID-19 confinement levels and sexual functioning domains in men and women, while accounting for the mediating role of psychological adjustment during lockdown. Two hundred and forty five men and 417 women completed a web survey on the effects of COVID-19 in sexual health. The reference period includes the first confinement in Portugal (March 19-June 1, 2020). Data were handled under Hays' procedures for simple mediation analysis. Measurement outcomes included self-reported levels of confinement, IIEF and FSFI scores, and psychological adjustment during lockdown. Psychological adjustment during lockdown mediated the relationship between confinement levels and most sexual functioning domains in men but not in women. Also, while confinement levels were not directly related with most sexual functioning domains, psychological adjustment during lockdown did predict lower sexual functioning in both genders. Findings support that human sexual functioning should be framed within a contextual perspective, emphasizing how psychological adjustment and situational life stressors, such as lockdown situations, shape individuals' sexuality. Such perspective should be considered in treatment protocols implemented during current pandemic. Data add to the literature on the effects of lockdown in the sexuality domain. However, the study precludes inference of causality and targets only a little proportion of all the dynamics involved in sexuality during the current historical moment. Psychological adjustment during COVID-19 seems to have a role on human sexual functioning, over the single effects of confinement. Carvalho J, Campos P, Carrito M, et al. The Relationship Between COVID-19 Confinement, Psychological Adjustment, and Sexual Functioning, in a Sample of Portuguese Men and Women. J Sex Med 2021;18:1191-1197.


A ridge regression approach to estimate the relationship between landfill taxation and waste collection and disposal in England.
The production of household waste is characterised by externalities and market failure, where the decision to consume does not consider the environmental impact of consequent waste generated. Policy interventions in the UK have focused primarily on pricing the disposal of waste through a landfill tax. This article tests the effectiveness of landfill taxation on household waste collection and disposal. Using a ridge regression with correction for fixed effects on a panel dataset of English local authorities, we estimate the landfill tax elasticity of waste for a range of waste disposal and collection streams. Results indicate that the landfill tax is elastic at disposal and effective in shifting waste from landfills to incineration. The tax is inelastic at collection, and encourages recycling. Our results indicate that landfill taxation is an important tool to change how waste is disposed by households and local authorities.


Continuous murmur caused by a ventricular septal defect post-myocardial infarction: visual display with a handheld computer.
Ventricular septal defects do not typically result in a continuous murmur. The only previously reported case involved a congenital ventricular septal defect. We report a case of an acquired ventricular septal defect following a large anterior myocardial infarction resulting in a continuous murmur. The continUous nature was confirmed both with 2D echocardiography and a specially equipped stethoscope in conjunction with a handheld computer to provide a visual display of the murmur. A proposed mechanism for the continuous murmur was discussed.


Efficacy and safety of tocilizumab in elderly patients with rheumatoid arthritis.
To assess the safety and efficacy of tocilizumab (TCZ) in elderly (≥65 years) rheumatoid arthritis (RA) patients treated in daily practice. We conducted a retrospective study of TCZ use in RA patients in five French university hospitals between 2009 and 2012. We considered two age groups, under 65 years (<65) and over 65 years (≥65). TCZ efficacy was evaluated at 24 weeks by the European League Against Rheumatism (EULAR) response and remission score. We also evaluated drug maintenance and safety, relative to adverse events discontinuation. A multivariate cumulative logit model for ordinal categories was performed to assess the relationship between age class and EULAR response (none, moderate and good) adjusted on possible confounders. TCZ retention (drug survival) over time was estimated with the Kaplan-Meier method. Treatment retention curves were compared according to age group with the log-rank test. Among 222 RA patients treated with TCZ, 61 (27.5%) were≥65 years at the initiation of treatment. After 6 months, this elderly patient group less often reached remission (27.8% versus 45.6%; P=0.02) or good EULAR response (40.7% versus 61.0%; P<0.01) compared to the younger patient group (<65). Multivariate analysis adjusted on baseline C-reactive protein and disease duration confirmed that elderly patients were more likely to have a lower EULAR response (none vs moderate-good or none-moderate vs good) (OR: 3.63; 95% CI [1.86-7.06], P<0.001) compared to younger patients. Drug maintenance for TCZ and adverse events discontinuation rates were similar between the two age groups. In daily practice, TCZ seems to be well tolerated in RA patients but is less efficient in elderly patients. A broader field of analysis to include an international register will be required to confirm these results.


Heme peroxidase activity measured in single mosquitoes identifies individuals expressing an elevated oxidase for insecticide resistance.
Optimum conditions are described for a simple, rapid, microplate-based assay that indirectly measures the differences in oxidase levels between individual susceptible, resistant, or induced mosquitoes. A small proportion (0.01-0.1) of a single mosquito is used, allowing multiple replicates of the oxidase assay. Cytochrome C is used as a positive control. The levels of oxidase found in sample populations of pyrethroid-susceptible, pyrethroid-resistant, and phenobarbital-induced Anopheles albimanus mosquitoes are characterized with the assay.


Predictive Analytics and the Return of "Research" Information to Participants.
The World Health Organization (WHO) estimates older adults aged 60+ will double by 2050 with 80% living in low to moderate income countries. As remote research studies supported by digital devices increase separation between researchers and participants, it is important to maintain participant trust. Research participants have expressed an interest in accessing both group and individual level results, which are not readily available. To bridge this gap, we engaged residents of a local continuing care senior housing community (CCSHC) to co-design documents used to convey information about study results. The process informed the refinement of informational materials for communicating scientific research that the CCSHC community considers accessible and meaningful.


Clinical features and prognosis of pediatric idiopathic sudden sensorineural hearing loss: A bi-center retrospective study.
Limited research has focused on the clinical features of sudden sensorineural hearing loss (SSNHL) in pediatric patients. This study is aimed to investigate the relationship between clinical features and the baseline hearing severity and outcomes of SSNHL in the pediatric population. We conducted a bi-center retrospective observational study in 145 SSNHL patients aged no more than 18 years who were recruited between November 2013 and October 2022. Data extracted from medical records, audiograms, complete blood count (CBC) and coagulation tests have been assessed for the relationship with the severity (the thresholds of the initial hearing) and outcomes (recovery rate, hearing gain and the thresholds of the final hearing). A lower lymphocyte count (P = 0.004) and a higher platelet-to-lymphocyte ratio (PLR) (P = 0.041) were found in the patient group with profound initial hearing than in the less severe group. Vertigo (β = 13.932, 95%CI: 4.082-23.782, P = 0.007) and lymphocyte count (β = -6.686, 95%CI: -10.919 to -2.454, P = 0.003) showed significant associations with the threshold of the initial hearing. In the multivariate logistic model, the probability of recovery was higher for patients with ascending and flat audiograms compared to those with descending audiograms (ascending: OR 8.168, 95% CI 1.450-70.143, P = 0.029; flat: OR 3.966, 95% CI 1.341-12.651, P = 0.015). Patients with tinnitus had a 3.2-fold increase in the probability of recovery (OR 3.222, 95% CI 1.241-8.907, P = 0.019), while the baseline hearing threshold (OR 0.968, 95% CI 0.936-0.998, P = 0.047) and duration to the onset of therapy (OR 0.942, 95% CI 0.890-0.977, P = 0.010) were negatively associated with the odds of recovery. The present study showed that accompanying tinnitus, the severity of initial hearing loss, the time elapse and the audiogram configuration might be related to the prognosis of pediatric SSNHL. Meanwhile, the presence of vertigo, lower lymphocytes and higher PLR were associated with worse severity.


An analytical process of spatial autocorrelation functions based on Moran's index.
A number of spatial statistic measurements such as Moran's I and Geary's C can be used for spatial autocorrelation analysis. Spatial autocorrelation modeling proceeded from the 1-dimension autocorrelation of time series analysis, with time lag replaced by spatial weights so that the autocorrelation functions degenerated to autocorrelation coefficients. This paper develops 2-dimensional spatial autocorrelation functions based on the Moran index using the relative staircase function as a weight function to yield a spatial weight matrix with a displacement parameter. The displacement bears analogy with the time lag in time series analysis. Based on the spatial displacement parameter, two types of spatial autocorrelation functions are constructed for 2-dimensional spatial analysis. Then the partial spatial autocorrelation functions are derived by using the Yule-Walker recursive equation. The spatial autocorrelation functions are generalized to the autocorrelation functions based on Geary's coefficient and Getis' index. As an example, the new analytical framework was applied to the spatial autocorrelation modeling of Chinese cities. A conclusion can be reached that it is an effective method to build an autocorrelation function based on the relative step function. The spatial autocorrelation functions can be employed to reveal deep geographical information and perform spatial dynamic analysis, and lay the foundation for the scaling analysis of spatial correlation.


Does your past define you? How weight histories are associated with child eating-disorder psychopathology.
To examine how parents' and adolescents' weight histories were associated with parents' approach to eating/weight-related parenting and children's eating-disorder behaviors. Participants were 502 parents (69.3% mothers, 30.7% fathers) of children 12-16 years old who completed an online survey. Parents reported their own and their child's weight status during childhood and adolescence. Parents' and children's weight histories were categorized as "weight loss," "weight stability," or "weight gain" and were examined in relation to feeding practices and eating-disorder psychopathology. Parents with a history of weight gain had greater personal eating-disorder psychopathology and more concerns about their child's weight than parents with weight stability or loss. They also reported greater parental overvaluation (judgment of themselves as parents according to their child's weight/shape). Children with a history of weight loss or gain were more likely to have eating-disorder behaviors than those with stable weight. Analyses revealed that results largely persisted after adjusting for child BMI-z. Both parent and child weight gain between childhood and adolescence were associated with eating-disorder psychopathology, eating/weight-related parenting, and feeding practices. Pediatricians and clinicians should assess weight history when considering risk for eating disorders and obesity. Level III, Evidence obtained from well-designed cohort or case-controlled analytic studies.


Silver-organic coordination networks for magnetic solid-phase extraction of trihalomethanes from environmental water samples: experimental and theoretical calculation study.
Trihalomethanes (THMs) are the primary toxic and carcinogenic byproducts during disinfection of drinking water. THMs have been frequently detected in water body and posed a huge threat to human health. Thus, analyzing the trace levels of THMs in an accurate and rapid method for water quality monitoring is important. In this paper, silver-based organic coordination networks (Ag-OCN) were fabricated with different diameters under mild pH condition. After modification with magnet, Fe3O4 @ Ag-OCN as extractant was applied to the magnetic solid-phase extraction of THMs from water samples. Gas chromatography-tandem mass spectrometry was used for sample quantification and detection. The magnetic extractant displayed good linearity in the range of 0.03-10 ug/L, low limits of detection (1.41-10.13 ng/L), and good reproducibility (relative standard deviations < 6.31%). Moreover, density-functional theory (DFT) calculation was also applied to investigate the possible interaction mechanism. Combining the experimental data with theoretical calculation, results showed that Fe3O4 @ Ag-OCN was a potential magnetic material for the enrichment and extraction of formed THMs at trace levels from water samples.


Comparison of three a-priori models in the prediction of serum lithium concentration.
Mathematical models are valuable for optimizing drug dose and dosing regimens. To compare the precision and bias of three a-priori methods in the prediction of serum level of lithium in patients with bipolar disorder, and to determine their sensitivity and specificity in detecting serum lithium levels outside the therapeutic range. Hospital-based, retrospective study. In a retrospective study of 31 in-patients, the serum level of lithium was calculated using three different a-priori methods. Mean Prediction Error was used as a measure of bias while Mean Absolute Error and Root Mean Squared Error were used as a measure of precision. The sensitivity and specificity of the methods was calculated. All three models underestimated serum lithium level. Precision was best with the model described by Pepin et al., while bias of prediction was the least with the method of Abou Auda et al. The formula by Pepin et al. was able to predict serum lithium level with a mean error of 36.57%. The sensitivity and specificity of the models in identifying serum lithium levels outside the therapeutic range was 80% and 76.19% for Pepin et al., 90% and 74.19% for Zetin et al., and 90% and 66.67% for Abou-Auda et al., respectively. The study demonstrates the difference in precision and bias of three a-priori methods, with no one method being superior to the other in the prediction of serum concentration.


8-hydroxy-2'-deoxyguanosine and cardiovascular disease: a systematic review.
Oxidative stress due to an excess of reactive oxygen species (ROS) may play a role in the development and progression of cardiovascular disease (CVD). 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a marker of oxidative DNA damage caused by ROS. This review aimed to assess the association between 8-OHdG and CVD by reviewing the literature. Studies in human subjects using either plasma or urine to determine 8-OHdG concentrations were surveyed. Eighteen relevant studies were found, of which 13 were case-control studies and five had a prospective design. Without exception, the case-control studies showed significant positive associations between 8-OHdG and CVD. In agreement, two prospective studies showed a significant association of 8-OHdG and heart failure. Furthermore, two prospective studies found a significant association between 8-OHdG and stroke, and finally, one prospective study showed a borderline significant (p = 0.08) association between coronary artery disease (CAD) patients developing a cardiac event and 8-OHdG concentrations. In conclusion, high levels of 8-OHdG in blood and urine are associated with atherosclerosis and heart failure, but further large prospective studies are needed to investigate 8-OHdG as a predictor for cardiovascular diseases.


Vitrectomy for full thickness macular hole developed during the course of anti-VEGF treatment of type 1 neovascular AMD.
To report a case of treatment of a full-thickness macular hole, which appeared after 10 months of anti-VEGF treatment in neovascular age related macular degeneration (nAMD). The patient was diagnosed as type 1 nAMD. The coexisting vitreomacular traction caused a full thickness macular hole after 10 months of treatment. A 68-year-old woman treated with anti VEGF. Vitrectomy with the temporal inverted ILM flap technique succeeded in closing the hole. Further anti-VEGF treatment followed. FTMH is a rare complication or coexistence in nAMD. Vitrectomy and continuous anti-VEGF treatment might result in satisfactory anatomical and functional results.


Interleukin-1 beta release from human peripheral blood monocytes associated with phagocytosis of carbonyl-iron or erythrocytes.
Interleukin-1 beta (IL-1 beta) release from human peripheral blood monocytes during the incubation with carbonyl-iron or sheep red blood cells was investigated. The incubation of purified monocytes with carbonyl-iron or sheep red blood cells enhanced IL-1 beta release, while their compounds, hemoglobin, globin and ferric citrate did not. The mechanisms of IL-1 beta release by carbonyl-iron or sheep red blood cells may be related to their phagocytosis, as non-phagocytic monocytes did not release IL-1 beta.


Short administration of polyclonal anti-T cell antibody (ALS) in NOD mice with extensive insulitis prevents subsequent development of autoimmune diabetes.
Treatment of overtly diabetic NOD mice with antilymphocyte serum (ALS), a polyclonal anti-T cell antibody, leads to cure of diabetes. Here, we investigated whether ALS-treatment of NOD mice after development of extensive insulitis prevents onset of diabetes. Female NOD mice were treated with two doses of ALS at 14, 19 or 23 weeks of age. No further treatment was given. In untreated female NOD mice, diabetes developed starting at 13 weeks and reached 68% by 37 weeks. ALS-treatment at 14, 19 or 23 weeks when histology showed progressive insulitis completely prevented onset of overt diabetes in 9/12, 11/12 or 12/12 mice, respectively. Intraperitoneal glucose tolerance tests in 43 week-old ALS-treated, diabetes-free mice showed a normal pattern. Co-adoptive transfer of lymphoid cells prepared from ALS-treated diabetes-free mice together with splenocytes from overtly diabetic NOD mice resulted in marked delay in diabetes onset in NOD.SCID mice, suggesting the presence of autoimmune regulatory cells in ALS-treated mice. Autoimmune regulatory cells were CD4(+)CD25(+), but not CD4(+)CD25(-), T cells. Thus, treatment of euglycemic individuals who already show signs of autoimmune diabetes with a short course of polyclonal anti-T cell antibody may effectively prevent onset of type 1 diabetes mellitus.


[Enzyme diagnostics in lysosomal diseases with emphasis on sphingolipidoses].
The authors describe the conditions and results of the enzymatic diagnosis in various sphingolipidoses, based on their personal experience. A precise diagnosis can be presently made on white blood cells, cultured fibroblasts or amniotic cells, and in some cases on serum or urine. In most cases the use of artificial substrates allows a relatively simple diagnosis. The methods are quantitative or qualitative (especially cellulose acetate electrophoresis, of which a few pictures are shown). The results are particularly clear in Tay-Sachs disease and its variants. Despite the fatal prognosis of most sphingolipidoses it is important to ensure a precise and precocious diagnosis. This is of prime value when a prenatal detection of the disease is considered in case of a future pregnancy.


Statin on post-stroke epilepsy: A systematic review and meta-analysis.
Recent research has shown that statins can reduce the incidence of epilepsy after stroke, especially ischemic stroke, but the results are inconsistent. In view of current stroke guidelines do not recommend the use of anti-epileptic drugs (AED) for the prevention of epilepsy after stroke, statins may be a good choice. The purpose of this study was to conduct a systematic review and meta-analysis to determine the effect of statins on the prevention of epilepsy after stroke. Correlative cohort studies were identified through search of PubMed, Cochrane Library and Embase databases. The main outcomes included post-stroke epilepsy (PSE) and early-onset seizure (ES). Subgroup analyses and Sensitivity analysis were performed to evaluate the influences of the predefined study characteristics on the outcome. Seven studies were included (n = 40831). Statin use was associated with a lower risk of PSE (including 6 articles) (odds ratio [OR] 0.60, 95% confidence interval [CI] [0.42, 0.84], p = 0.003), and there is a remarkable effect in ES (including 6 articles) (OR 0.36, 95% CI [0.25, 0.54], p < 0.00001). Appropriate use of statins after stroke can reduce the risk of PSE, especially ES.


Usefulness of the Cryolife O'Brien stentless suprannular aortic valve to prevent prosthesis-patient mismatch in the small aortic root.
This study evaluated the occurrence of prosthesis-patient mismatch (PPM) after Cryolife O'Brien (CLOB) suprannular stentless valve replacement in patients with a small aortic root and its repercussions on the patient's hemodynamic status and left ventricular mass regression. The correct management of the small aortic annulus is still controversial. Small aortic prostheses can lead to a PPM, which results in high gradients with important repercussions on the hemodynamic status. Seventy-two patients (mean age: 72.5 +/- 6.2 years, 73.6% women) with a small aortic root (< or =21 mm intraoperatively measured aortic annulus) had a CLOB valve implanted in the aortic position between November 1993 and July 2001 at our institution. Mean prosthesis size was 22.0 +/- 0.8 mm. Patients underwent echocardiography preoperatively, at discharge, six months, one year and yearly thereafter. The incidence of PPM at discharge was 22.2% (16/72); 18.7% were severe (effective orifice area index [EOAI] < or =0.65 cm/m(2)), 43.7% were moderate (EOAI = 0.66 to 0.75 cm/m(2)) and 37.6% were mild (0.76 to 0.85 cm/m(2)). At multivariable analysis, gender (p < 0.001), age (p = 0.015), body surface area (p < 0.001) and patient's annulus index (p < 0.001) were significant factors influencing the occurrence of "transient" PPM. At one year the incidence of PPM was 0%. CONCLUSIONS; Suprannular CLOB valve yielded excellent hemodynamic results in patients with small aortic roots. This study demonstrates that PPM can be completely avoided when using the CLOB valve. The superior hemodynamics of this stentless valve are likely to be related to its suprannular design.


Nucleotide sequence analysis of the S genomic segment of Prospect Hill virus: comparison with the prototype Hantavirus.
The genomic S RNA segment of Prospect Hill virus (PHV), a member of the Hantavirus genus, was molecularly cloned and the nucleotide sequence of the cDNA determined. The PHV S RNA segment is 1675 nucleotides long. A long open reading frame was identified in the viral complementary-sense RNA that could encode a 433 amino acid (49K) nucleocapsid (N) protein. Comparison with the sequence of the related Hantavirus (Hantaan 76-118) S RNA segment indicated that there was 57% nucleotide sequence homology between the two S RNA segments. A higher degree of conservation in amino acid sequence homology (62%) was observed in the N proteins of these viruses. At the N-terminus 147 of 225 amino acids are homologous, while approximately 82% of the 124 amino acids at the C-terminus are homologous between the two N proteins. The longest stretch of homologous amino acid sequence is found in this region, and is 17 amino acids in length. Also, many of the differences in amino acid sequence between the two N proteins resulted from conservative substitutions. Hydropathy plots of the two N proteins also reveal many similarities including a conserved potential antigenic site. Unlike Hantaan virus, a second smaller overlapping open reading frame was observed in the viral complementary-sense RNA of PHV and could potentially encode a 90 amino acid (10.5K) protein. Our data indicate that the N proteins of PHV and Hantaan virus are closely related despite divergence in the nucleotide sequence of their S RNA segments.


Evaluation of the anthelmintic effects of artesunate against experimental Schistosoma mansoni infection in mice using different treatment protocols.
The therapeutic effects of artesunate against experimental Schistosoma mansoni infection in mice were analyzed. Previous studies showed that artesunate is highly effective against S. japonicum infection, but the action of this drug against S. mansoni remained uncovered. The present study examines the optical conditions for artesunate against S. mansoni and evaluates the effects of inhibiting the sexual maturation of adult worms. Mice infected with S. mansoni were orally administered with artesunate according to different schedules. Four consecutive administrations of 300 mg/kg of artesunate at 2-week intervals conferred almost total protection without the development of pathological lesions in the liver. The significant reduction in the number of eggs produced by surviving worms and the status of egg maturation suggested that artesunate inhibits sexual maturation. Electron microscopy revealed that artesunate caused morphological damage, especially on the worm tegument. Artesunate was also very effective in iron-deficient mice. Furthermore, the efficacy of artesunate was equal to or better than that of artemether against S. japonicum infection. Considering that artemether is more toxic, artesunate is currently one of the most efficient drugs against immature S. mansoni.


Analysis of essential and non-essential trace elements in the organs of a mother-fetus pair of spotted seals (Phoca largha) from the Sea of Japan.
Concentrations of 22 essential and non-essential trace elements (Be, Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Mo, Ag, Cd, Sb, Ba, Tl, Pb, Th, U, and Hg) were measured in the organs of a mother-fetus pair (at the last trimester of pregnancy) of spotted seals from the Sea of Japan. The concentrations of eleven elements are reported for the first time. Eight organs of the pair were examined: lungs, heart, liver, kidneys, intestines, spleen, muscles, and bones. All trace elements detected in the organs of the mother were found also in the organs of the fetus at various concentrations. Placenta is not an effective barrier to prevent non-essential elements from getting into the fetus, but can control entry of some of them, e.g., aluminum, cadmium, and mercury. In most organs of the fetus, the concentrations of toxic trace elements (beryllium, antimony, thorium, and uranium) were noticeably higher than in the same organs of the mother, which indicates that during pregnancy female removes excess of non-essential trace elements by transferring them to the fetal body through the placental barrier.


Simultaneous delivery of hydrophobic small molecules and siRNA using Sterosomes to direct mesenchymal stem cell differentiation for bone repair.
The use of small molecular drugs with gene manipulation offers synergistic therapeutic efficacy by targeting multiple signaling pathways for combined treatment. Stimulation of mesenchymal stem cells (MSCs) with osteoinductive small molecule phenamil combined with suppression of noggin is a promising therapeutic strategy that increases bone morphogenetic protein (BMP) signaling and bone repair. Our cationic Sterosome formulated with stearylamine (SA) and cholesterol (Chol) is an attractive co-delivery system that not only forms stable complexes with small interfering RNA (siRNA) molecules but also solubilizes hydrophobic small molecules in a single vehicle, for directing stem cell differentiation. Herein, we demonstrate the ability of SA/Chol Sterosomes to simultaneously deliver hydrophobic small molecule phenamil and noggin-directed siRNA to enhance osteogenic differentiation of MSCs both in in vitro two- and three-dimensional settings as well as in a mouse calvarial defect model. These results suggest a novel liposomal platform to simultaneously deliver therapeutic genes and small molecules for combined therapy. Application of phenamil, a small molecular bone morphogenetic protein (BMP) stimulator, combined with suppression of natural BMP antagonists such as noggin is a promising therapeutic strategy to enhance bone regeneration. Here, we present a novel strategy to co-deliver hydrophobic small molecule phenamil and noggin-targeted siRNA via cationic Sterosomes formed with stearylamine (SA) and high content of cholesterol (Chol) to enhance osteogenesis and bone repair. SA/Chol Sterosomes demonstrated high phenamil encapsulation efficiency, supported sustained release of encapsulated drugs, and significantly reduced drug dose requirements to induce osteogenic differentiation of mesenchymal stem cells (MSCs). Simultaneous deliver of phenamil and noggin siRNA in a single vehicle synergistically enhanced MSC osteogenesis and calvarial bone repair. This study suggests a new non-phospholipid liposomal formulation to simultaneously deliver small molecules and therapeutic genes for combined treatment.


Resilience of Andean urban ethnobotanies: a comparison of medicinal plant use among Bolivian and Peruvian migrants in the United Kingdom and in their countries of origin.
Analysing why and how ethnobotanical traditions 'survive' is important for a better understanding of migrants' health care behaviour. This study investigates the use of traditional medicinal plants among first generation migrants from Bolivia and Peru in London, in relation to practices among their peers in their respective home countries in order to assess changes in traditional health care among newcomer communities. A total of 98 semi-structured interviews were conducted in London (UK), Cochabamba (Bolivia) and Lima (Peru). Voucher specimens of all reported species were collected and identified. By comparing data on active plant uses and their applications, overlap and differences between health care practices before and after migration could be outlined. In London, people can rely on more biomedical alternatives and have access to less traditional herbal remedies as compared to their countries of origin. In general, Peruvians and Bolivians in London continued to use traditional medicine for common, self-limiting ailments that were also widespread in their countries of origin. The same widely used (either readily available cosmopolitan or culturally relevant) plant species appeared in the post-migration group. In general, less freshly available medicinal species were used in London and more edible, primary food species were consumed for medicinal purposes after migration. Bolivian and Peruvian migrants in London clearly proved to be resilient in their use of home-remedies when faced with the changes that come with migration. The observed ethnobotanical coping strategies are characterised by: (1) the preservation of culturally salient species (cultural key stone species); (2) a positive influence of the presence of cultural diversity (cultural edge effect), (3) a creative blending of different kinds of knowledge and resources, noticeable in an increased use of dried, processed alternatives and food species; and (4) a reliance on social networks for the exchange of plant material.