[Noninvasive methods of the examination in surgery of obliterating atherosclerosis of lower extremity arteries].
The purpose of the study was to determine surgical policy in atherosclerotic lesions of aorta and lower extremities arteries on the basis on non-invasive diagnostic methods--duplex scanning (DS) and computer tomographic angiography (CTA). From 1998 to 1999 47 patients were examined on this program (DS + CTA). At the first stage of the study, 17 patients underwent translumbal aorto-arteriography at the same time with DS and CTA. Analysis of the angiograms revealed that sensitivity of angiography for detection of lesions in aorto-iliac segment was 94%, in femoro-popliteal segment--78%. Diagnostic mistakes were associated with partial thrombosis of aneurysm's lumen, as a result of which the aorta looked non-dilated in angiograms. Femoral arteries contrasted unsatisfactory in 4 patients because of low collateral blood velocity distal to occlusion of iliac arteries. Initial segments of deep and superficial femoral arteries closed each other in angiograms on anterior-posterior projection, and it also led to low potential of angiography in assessment of femoral arteries state. Complex of non-invasive diagnostic methods (DS + CTA) allowed to correct diagnosis in each case. The methods complemented one another: CTA permitted to make three-dimensional reconstruction of vascular tree and to study its on various projections; DS--to study the vascular wall's state and hemodynamical parameters of blood flow. At the second stage of the study, high sensitivity of DS and CTA allowed to reject traditional angiography in preoperative period. Intraoperative findings confirmed the provisional diagnosis completely.


Attachment style, affective loss and gray matter volume: a voxel-based morphometry study.
Early patterns of infant attachment have been shown to be an important influence on adult social behavior. Animal studies suggest that patterns of early attachment influence brain development, contributing to permanent alterations in neural structure; however, there are no previous studies investigating whether differences in attachment style are associated with differences in brain structure in humans. In this study, we used Magnetic Resonance Imaging (MRI) and voxel-based morphometry (VBM) to examine for the first time the association between attachment style, affective loss (for example, death of a loved one) and gray matter volume in a healthy sample of adults (n = 32). Attachment style was assessed on two dimensions (anxious and avoidant) using the ECR-Revised questionnaire. High attachment-related anxiety was associated with decreased gray matter in the anterior temporal pole and increased gray matter in the left lateral orbital gyrus. A greater number of affective losses was associated with increased gray matter volume in the cerebellum; in this region, however, the impact of affective losses was significantly moderated by the level of attachment-related avoidance. These findings indicate that differences in attachment style are associated with differences in the neural structure of regions implicated in emotion regulation. It is hypothesized that early attachment experience may contribute to structural brain differences associated with attachment style in adulthood; furthermore, these findings point to a neuronal mechanism through which attachment style may mediate individual differences in responses to affective loss.


[The effect of sodium oxybutyrate on various regulatory mechanisms of pulmonary hemodynamics in experimental tuberculosis in dogs].
The role of cyclic nucleotides and prostaglandins E1 and F2 alpha in pulmonary hypertension formation was elucidated in experimental tuberculosis in dogs and the mechanism of a hypotensive action of sodium oxybutyrate specified with consideration of its influence on the non-gas exchange pulmonary function. The level of the above compounds was studied in the blood taken from the pulmonary artery and aorta in comparison with pulmonary artery pressure prior to and after intravenous injection of sodium oxybutyrate, an antihypoxant. Pulmonary vessel tone was found to depend on the cGMP content and synthesis in the lungs both in health and in tuberculosis and pulmonary hypertension in tuberculosis was associated with a deranged level and correlation of cAMP, cGMP and prostaglandins E1 and F2 alpha in pulmonary circulation. It has been demonstrated that the hypotensive effect of sodium oxybutyrate is associated with its influence on these biochemical parameters in plasma.


Risk Factors Predicting Positive Margins at Primary Wide Local Excision of Cutaneous Melanoma.
A small percentage of patients will have positive histological margins after primary wide local excision (WLE) of cutaneous melanoma (CM). Risk factors that predict marginal involvement at WLE remain unclear. To identify risk factors associated with positive margins after WLE of CM. A retrospective review of patients treated at a single institution for CM with sentinel lymph node biopsy from 1997 to 2011 was conducted. Positive margins occurred in 6% of patients. Patients with positive margins were older (72.4 vs 60.7, p < .001), had thicker tumors (3.6 vs 1.9 mm, p < .001), and often involved the head and neck region (p < .001). Patients with positive margins at WLE had positive margins on initial biopsy (p = .012) and a higher rate of a melanoma in situ component on initial biopsy (24% vs 11%, p = .02). The 5-year local recurrence rate was significantly different between those with positive and negative margins at WLE (16.0% vs 6.9%; p = .047). Positive margins after WLE are uncommon. When a patient has multiple risk factors for positive margins at WLE, histologically clear margins should be obtained through mapped serial excision or Mohs micrographic surgery.


Preliminary report of two-stage secondary alveolar bone grafting for patients with bilateral cleft lip and palate.
To overcome the difficulties of one-stage secondary alveolar bone grafting for patients with bilateral cleft lip and palate (BCLP) who have a broad alveolar cleft, the value of two-stage alveolar bone grafting was examined. Three patients (2 girls and 1 boy) with BCLP were treated by two-stage alveolar bone grafting. The procedure consisted of a first-stage surgery (mean age 8 year 6 months +/- 7.8 months), which consisted of alveolar bone grafting for one side of the BCLP, and second-stage surgery for the contralateral side several months later. For the postoperative assessment, radiographs of the operated site were examined. The average amount of implanted bone per operation and per patient was 6.8 +/- 1.1 g and 13.7 +/- 1.0 g, respectively. Postoperative clinical and radiographic examinations revealed that an appreciable alveolar bone ridge had formed, and there were no major complications. Two-stage alveolar bone grafting, which makes it possible to reduce the amount of implanted bone, could be an optional surgical procedure for patients with BCLP and a broad alveolar cleft.


Enhanced drinking after excitotoxic lesions of the parabrachial nucleus in the rat.
Previous reports indicate the lateral parabrachial nucleus (IPBN) is important in the regulation of fluid intake. After electrolytic lesions of the IPBN, rats consume increased amounts of water when challenged with pharmacological stimuli that mimic depletion of the extracellular fluid space. Nonetheless, it is possible that neurons within the IPBN are not responsible for the overingestion of water during extracellular thirst challenges, since electrolytic lesions damage fibers of passage as well as neurons within the IPBN. Thus we used the excitatory neurotoxin ibotenic acid to lesion cell bodies within the IPBN. After recovery from surgery, water consumption by lesioned rats was significantly greater than consumption by vehicle or uninjected control rats when challenged with subcutaneous angiotensin II or isoproterenol to stimulate drinking. However, when injected with subcutaneous hypertonic saline to produce cellular dehydration, or when water deprived for 24 h, the water intake of rats with lesions was not different from the intake of control rats. Anatomical examination of the lesion sites revealed that ibotenic acid injection caused a notable loss of neurons in the IPBN with little or no damage to surrounding structures. Moreover, injection of an anterograde tracer into the dorsomedial medulla resulted in labeling of fibers that traverse the ibotenic acid lesion site. Together, these data suggest neurons within the IPBN are involved in the regulation of fluid intake, particularly challenges that involve depletion of the extracellular fluid space.


Distributed smart device for monitoring, control and management of electric loads in domotic environments.
This paper presents a microdevice for monitoring, control and management of electric loads at home. The key idea is to compact the electronic design as much as possible in order to install it inside a Schuko socket. Moreover, the electronic Schuko socket (electronic microdevice + Schuko socket) has the feature of communicating with a central unit and with other microdevices over the existing powerlines. Using the existing power lines, the proposed device can be installed in new buildings or in old ones. The main use of this device is to monitor, control and manage electric loads to save energy and prevent accidents produced by different kind of devices (e.g., iron) used in domestic tasks. The developed smart device is based on a single phase multifunction energy meter manufactured by Analog Devices (ADE7753) to measure the consumption of electrical energy and then to transmit it using a serial interface. To provide current measurement information to the ADE7753, an ultra flat SMD open loop integrated circuit current transducer based on the Hall effect principle manufactured by Lem (FHS-40P/SP600) has been used. Moreover, each smart device has a PL-3120 smart transceiver manufactured by LonWorks to execute the user's program, to communicate with the ADE7753 via serial interface and to transmit information to the central unit via powerline communication. Experimental results show the exactitude of the measurements made using the developed smart device.


The penetration of topically applied ointment containing hyaluronic acid in rabbit tissues.
The properties of hyaluronic acid used for treatment of acute and chronic joint disease are known for many years and this compound is widely used both in humans and animals. To obtain a therapeutic effect of a certain drug, the appropriate concentration in the target organ or tissue is important. The application of labeled compounds is one of the frequently applied techniques to estimate drug penetration into the skin and other body tissues or organs. The aim of the study was to evaluate the penetration of hyaluronic acid labeled with I-131 through the skin and its distribution within the knee joint and other internal organs in rabbits after a topical application of an ointment containing hyaluronic acid. The experiment was performed on 22 albino rabbits divided into control and examined groups. Fifteen rabbits were exposed to the multicomponent ointment containing hyaluronic acid labeled with I-131. Time of exposure was 48 hours. Hyaluronate penetrated to a high degree into the examined tissues. No significant differences in terms of leg tissue activity were observed between a leg tissue exposed to labeled ointment and that unexposed, suggesting that after topical administration, the active component of the ointment is delivered to the joint via the blood stream. Hyaluronate applied topically penetrates through the skin into the rabbit tissues and organs and into the joint fluid of both legs (exposed and not exposed). This route of administration seems to be useful for this drug delivery and allows to avoid unnecessary side effects.


How does the Internet of Things (IoT) help in microalgae biorefinery?
Microalgae biorefinery is a platform for the conversion of microalgal biomass into a variety of value-added products, such as biofuels, bio-based chemicals, biomaterials, and bioactive substances. Commercialization and industrialization of microalgae biorefinery heavily rely on the capability and efficiency of large-scale cultivation of microalgae. Thus, there is an urgent need for novel technologies that can be used to monitor, automatically control, and precisely predict microalgae production. In light of this, innovative applications of the Internet of things (IoT) technologies in microalgae biorefinery have attracted tremendous research efforts. IoT has potential applications in a microalgae biorefinery for the automatic control of microalgae cultivation, monitoring and manipulation of microalgal cultivation parameters, optimization of microalgae productivity, identification of toxic algae species, screening of target microalgae species, classification of microalgae species, and viability detection of microalgal cells. In this critical review, cutting-edge IoT technologies that could be adopted to microalgae biorefinery in the upstream and downstream processing are described comprehensively. The current advances of the integration of IoT with microalgae biorefinery are presented. What this review discussed includes automation, sensors, lab-on-chip, and machine learning, which are the main constituent elements and advanced technologies of IoT. Specifically, future research directions are discussed with special emphasis on the development of sensors, the application of microfluidic technology, robotized microalgae, high-throughput platforms, deep learning, and other innovative techniques. This review could contribute greatly to the novelty and relevance in the field of IoT-based microalgae biorefinery to develop smarter, safer, cleaner, greener, and economically efficient techniques for exhaustive energy recovery during the biorefinery process.


Review of anticoagulation considerations in extracorporeal membrane oxygenation support.
Since its first success in 1975, extracorporeal membrane oxygenation (ECMO) has been used with increasing frequency for pulmonary and cardiopulmonary bypass. Use in adults has increased exponentially since the early 2000s, but despite thousands of international cannulations using both veno-arterial (VA) and veno-venous (VV) ECMO, there are still significant hemocompatibility-related adverse events. Current management of anticoagulation has been based on the Extracorporeal Life Support Organization guidance published in 2014 with recent updates published in 2022. Despite this guidance, there is still limited international consensus on how to manage anticoagulation in ECMO. For this review, we completed a comprehensive search of multiple electronic databases to identify studies pertaining to anticoagulation of adult patients on VV or VA-ECMO. The highest priority was given to sources that were prospective, randomized, controlled studies, but in the absence of such resources, observational studies, retrospective uncontrolled studies, and case series/reports were considered for inclusion. This document serves to provide a comprehensive review of the current understanding of management pertaining to anticoagulation relating to ECMO.


Behavior upset in hypertensive and normotensive black female caregivers.
While emotional reactions have been associated with higher systolic and diastolic blood pressure, this phenomenon has received little attention among caregivers of the elderly especially black caregivers. Therefore, the purpose of this pilot study was to explore and compare the levels of caregiver upset among hypertensive and normotensive black female caregivers. Ten hypertensive and eight normotensive black female caregivers of elderly persons were recruited specifically for this study. Data on the subjects' daily hassles, caregiving demands, and resources were collected by means of face-to-face interviews. While hypertensive and normotensive caregivers reported equivalent levels of daily hassles, and resources, they differed significantly in their emotional reactions to the care recipients' behavior. Hypertensive caregivers reported higher levels of caregiving demands and more upsets with the behavior of the care recipients. These findings suggest that nurses must assess not only the caregiving situation but also the caregiver's appraisal, especially among hypertensive black caregivers, since blacks have an earlier onset and greater severity of hypertension than whites.


Rapid and specific duplex detection of methicillin-resistant Staphylococcus aureus genes by surface-enhanced Raman spectroscopy.
Methicillin-resistant Staphylococcus aureus (MRSA) is considered to be one of the important hospital-acquired pathogens. MRSA is also commonly associated with hospital-acquired infections and mortality. Quantitative and precise detection of MRSA is essential for rapid diagnosis and subsequent effective disease management strategies. We herein developed a highly specific method for rapid MRSA detection that combines surface-enhanced Raman spectroscopy (SERS) nanotags and polymerase chain reaction (PCR). SERS provided the sensitivity and spectral multiplexing capability while PCR provided the specificity required for the assay. The method was tested by the simultaneous detection of two MRSA specific genes (mecA and femA) amplified from genomic DNA isolated from clinical specimens. Magnetic isolation and rapid duplex detection were performed to obtain a detectable signal down to 104 input copies within 80 min. This demonstrated the potential of the SERS-PCR based approach for the accurate identification of MRSA at an early-diagnosis stage. This study also provides an alternative approach to the existing methods for detecting clinical targets without compromising sensitivity and selectivity, and with minimal handling steps. We thus believe that this approach will find a broad application in clinical applications.


Critical periods in Drosophila neural network development: Importance to network tuning and therapeutic potential.
Critical periods are phases of heightened plasticity that occur during the development of neural networks. Beginning with pioneering work of Hubel and Wiesel, which identified a critical period for the formation of ocular dominance in mammalian visual network connectivity, critical periods have been identified for many circuits, both sensory and motor, and across phyla, suggesting a universal phenomenon. However, a key unanswered question remains why these forms of plasticity are restricted to specific developmental periods rather than being continuously present. The consequence of this temporal restriction is that activity perturbations during critical periods can have lasting and significant functional consequences for mature neural networks. From a developmental perspective, critical period plasticity might enable reproducibly robust network function to emerge from ensembles of cells, whose properties are necessarily variable and fluctuating. Critical periods also offer significant clinical opportunity. Imposed activity perturbation during these periods has shown remarkable beneficial outcomes in a range of animal models of neurological disease including epilepsy. In this review, we spotlight the recent identification of a locomotor critical period in Drosophila larva and describe how studying this model organism, because of its simplified nervous system and an almost complete wired connectome, offers an attractive prospect of understanding how activity during a critical period impacts a neuronal network.


Improving networks between acute care nurses and an aged care assessment team.
Acute care nurses have an important role in the discharge planning of older people from hospital to home. However, few nurses understand the changing aged care system or the consequences of poor referral on the lives of older people postdischarge. This paper reports the findings of a research project, which aimed to investigate the possibilities for facilitating the transition of older people from hospital to home through improving the working relationship between nurses and members of a multidisciplinary aged care assessment team (ACAT). The paper reports one action research cycle from a larger project. Action research was chosen because its focus on knowledge development and action leads to practical solutions to clinical problems. The research approach included interactive forums designed to facilitate effective collaboration between the nurses and ACAT in the discharge planning of older people. Data collection strategies included audiotapes of ACAT research discussions, field notes, policy documents, referral forms and an evaluation tool. The findings illustrate that ward nurses have, at best, a limited knowledge and understanding of the aged care system, its function, or how to access services. They need assistance to develop their knowledge of services available to support older people following discharge. The conduct of interactive forums, which utilize a case study approach, facilitated such knowledge development and empowered the nurses to become more involved in discharge planning. Participation in the forums also facilitated new collaborative partnerships between the nurses and ACAT, which enhanced effective discharge planning. The paper outlines practical strategies to support collaboration between ward nurses and community providers and/or multi disciplinary assessment services. It provides a list of key considerations for the development of effective ward/community networks to facilitate the discharge of older people.


Analysis of turnaround times in pathology: an approach using failure time analysis.
This article introduces the use of failure time analysis methods for studying turnaround times in pathology. The key to understanding the approach is to view a laboratory specimen like a living patient. When the specimen enters the laboratory, the time is analogous to the time of diagnosis for a patient. When the specimen's analysis is completed, the event is analogous to a patient who has died. To illustrate the approach, I use data previously published and data generated at the Durham, NC, Veterans Affairs Medical Center. I demonstrate that the Kaplan-Meier plotting method, the log-rank test, and the Cox model can all be applied to turnaround times and provide useful results.


Personality dimensions and emotional problems: the mediating role of irrational beliefs in Pakistani adult non-clinical sample.
This study presents the first examination of the relation between the Big Five personality traits, irrational beliefs and emotional problems in Pakistan, which is an understudied country in the psychological distress literature. A total of 195 participants (aged 25-60 years), employees at COMSATS University, completed a demographic information sheet, the Big Five Personality Questionnaire, the Irrational Belief Inventory and two subscales of the Brief Symptom Inventory including depression and anxiety. Direct effects of neuroticism, openness and conscientiousness were also observed for depression and anxiety. Structural Equation Modelling demonstrated that irrational beliefs played a significant mediating role in the relationship between neuroticism and anxiety and neuroticism and depression. The results highlight the importance of cognitive beliefs in functionally linking personality traits and emotional problems.


Hemoglobin heterogeneity and the oxygen affinity of the hemolysate of some Victoria cichlids.
The hemoglobin patterns of ten cichlid species from Lake Victoria were characterized by polyacrylamide gel electrophoresis. In all tested species the hemoglobin bands display the same electrophoretic mobility. Oxygen equilibria of the purified hemoglobin solution of five species were determined under standardized conditions (pH 7.4 at 20 degrees C). The analysed hemolysates have a relatively high oxygen affinity and for all the tested species the Hill coefficient approached unity. The effect of temperature on the oxygen affinity of Haplochormis "velvet black" hemolysate was determined at 20, 25, 30 and 35 degrees C. The obtained results (delta H value-68 kJ/mol) at pH 8.2 is comparable with earlier published results for other African and South American Cichlidae. The Bohr effect (phi = delta log P50/delta pH = -0.18 between pH 6.6-7.4 at 25 degrees C) proved to be lower than so far reported in other Cichlidae.


Position of the Academy of Nutrition and Dietetics: Benchmarks for Nutrition in Child Care.
It is the position of the Academy of Nutrition and Dietetics that early care and education (ECE) programs should achieve recommended benchmarks to meet children's nutrition needs and promote children's optimal growth in safe and healthy environments. Children's dietary intake is influenced by a number of factors within ECE, including the nutritional quality of the foods and beverages served, the mealtime environments, and the interactions that take place between children and their care providers. Other important and related health behaviors that may influence the development of obesity include children's physical activity, sleep, and stress within child care. Recent efforts to promote healthy eating and improve other health behaviors in ECE include national, state, and local policy changes. In addition, a number of interventions have been developed in recent years to encourage healthy eating and help prevent obesity in young children in ECE. Members of the dietetics profession, including registered dietitian nutritionists and nutrition and dietetics technicians, registered, can work in partnership with ECE providers and parents to help promote healthy eating, increase physical activity, and address other important health behaviors of children in care. Providers and parents can serve as role models to support these healthy behaviors. This Position Paper presents current evidence and recommendations for nutrition in ECE and provides guidance for registered dietitian nutritionists; nutrition and dietetics technicians, registered; and other food and nutrition practitioners working with parents and child-care providers. This Position Paper targets children ages 2 to 5 years attending ECE programs and highlights opportunities to improve and enhance children's healthy eating while in care.


MR evaluation of early myelination patterns in normal and developmentally delayed infants.
This study demonstrates the ability of MR imaging to show progression of myelination in 64 infants and young children (ages 4 days to 36 months). T2-weighted spin-echo pulse sequences, frequently used for routine screening of intracranial disease, were used. Gray-white matter differentiation was seen in all patients, and changes occurring with age were documented. Three distinct patterns were seen, and age ranges were established for each pattern in developmentally normal children: (1) infantile (birth-6 months); (2) isointense (8-12 months); and (3) early adult (10 months onward). There was a statistically significant difference between the age ranges of the normal and developmentally delayed children showing all three patterns. These data should be helpful for identifying and following sequentially both infants with clinically suspected developmental delay and those with dysmyelinating or demyelinating disease.


Detection of pediatric cervical spine injury.
In evaluating the pediatric cervical spine for injury, the use of adult protocols without sufficient sensitivity to pediatric injury patterns may lead to excessive radiation doses. Data on injury location and means of detection can inform pediatric-specific guideline development. We retrospectively identified pediatric patients with codes from the International Classification of Diseases, 9th Revision, for cervical spine injury treated between 1980 and 2000. Collected data included physical findings, radiographic means of detection, and location of injury. Sensitivity of plain x-rays and diagnostic yield from additional radiographic studies were calculated. Of 239 patients, 190 had true injuries and adequate medical records; of these, 187 had adequate radiology records. Patients without radiographic abnormality were excluded. In 34 children younger than 8 years, National Emergency X-Radiography Utilization Study criteria missed two injuries (sensitivity, 94%), with 76% of injuries occurring from occiput-C2. In 158 children older than 8 years, National Emergency X-Radiography Utilization Study criteria identified all injured patients (sensitivity, 100%), with 25% of injuries occurring from occiput-C2. For children younger than 8 years, plain-film sensitivity was 75% and combination plain-film/occiput-C3 computed tomographic scan had a sensitivity of 94%, whereas combination plain-film and flexion-extension views had 81% sensitivity. In patients older than 8 years, the sensitivities were 93%, 97%, and 94%, respectively. Younger children tend to have more rostral (occiput-C2) injuries compared with older children. The National Emergency X-Radiography Utilization Study protocol may have lower sensitivity in young children than in adults. Limited computed tomography from occiput-C3 may increase diagnostic yield appreciably in young children compared with flexion-extension views. Further prospective studies, especially of young children, are needed to develop reliable pediatric protocols.


Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia.
The lung pathology seen in patients with coronavirus disease 2019 (COVID-19) shows marked microvascular thrombosis and haemorrhage linked to extensive alveolar and interstitial inflammation that shares features with macrophage activation syndrome (MAS). We have termed the lung-restricted vascular immunopathology associated with COVID-19 as diffuse pulmonary intravascular coagulopathy, which in its early stages is distinct from disseminated intravascular coagulation. Increased circulating D-dimer concentrations (reflecting pulmonary vascular bed thrombosis with fibrinolysis) and elevated cardiac enzyme concentrations (reflecting emergent ventricular stress induced by pulmonary hypertension) in the face of normal fibrinogen and platelet levels are key early features of severe pulmonary intravascular coagulopathy related to COVID-19. Extensive immunothrombosis over a wide pulmonary vascular territory without confirmation of COVID-19 viraemia in early disease best explains the adverse impact of male sex, hypertension, obesity, and diabetes on the prognosis of patients with COVID-19. The immune mechanism underlying diffuse alveolar and pulmonary interstitial inflammation in COVID-19 involves a MAS-like state that triggers extensive immunothrombosis, which might unmask subclinical cardiovascular disease and is distinct from the MAS and disseminated intravascular coagulation that is more familiar to rheumatologists.


Adherence to and invasion of human intestinal cells by Arcobacter species and their virulence genotypes.
The genus Arcobacter is composed of 17 species which have been isolated from various sources. Of particular interest are A. butzleri, A. cryaerophilus, and A. skirrowii, as these have been associated with human cases of diarrhea, the probable transmission routes being through the ingestion of contaminated drinking water and food. To date, only limited studies of virulence traits in this genus have been undertaken. The present study used 60 Arcobacter strains isolated from different sources, representing 16 of the 17 species of the genus, to investigate their ability to adhere to and invade the human intestinal cell line Caco-2. In addition, the presence of five putative virulence genes (ciaB, cadF, cj1349, hecA, and irgA) was screened for in these strains by PCR. All Arcobacter species except A. bivalviorum and Arcobacter sp. strain W63 adhered to Caco-2 cells, and most species (10/16) were invasive. The most invasive species were A. skirrowii, A. cryaerophilus, A. butzleri, and A. defluvii. All invasive strains were positive for ciaB (encoding a putative invasion protein). Other putative virulence genes were present in other species, i.e., A. butzleri (cadF, cj1349, irgA, and hecA), A. trophiarum (cj1349), A. ellisii (cj1349), and A. defluvii (irgA). No virulence genes were detected in strains which showed little or no invasion of Caco-2 cells. These results indicate that many Arcobacter species are potential pathogens of humans and animals.


Alcohol use and psychiatric comorbid disorders predict deliberate self-harm behaviour and other suicidality among depressed adolescent outpatients in 1-year follow-up.
Suicidality, including deliberate self-harm behaviour (DSH), represents one of the most adverse and clinically serious consequences of depression. More detailed longitudinal research is needed in order to find clinical risk factors of DSH and other suicidal behaviour among depressed adolescent outpatients in order to identify those at greatest risk of life-threatening behaviour. This follow-up study investigated alcohol use, Axis I comorbid disorders, depressive and anxiety symptoms, and psychosocial functioning as risk factors of suicidal behaviour, including DSH, among depressed adolescent outpatients during a 1-year follow-up. Consecutive depressed adolescent outpatients (n = 189) aged 13-19 years were interviewed at baseline and at follow-up by using the Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime (K-SADS-PL) for DSM-IV Axis I diagnoses and self-report questionnaires. Suicidal behaviour was assessed by K-SADS suicidality items. During 1-year follow-up, one-quarter of all participants, and almost three-quarters of suicidal adolescents had DSH. Alcohol use and mood disorder with Axis I comorbidity at baseline predicted both DSH and other suicidal behaviour during follow-up. Mood disorder during follow-up predicted all forms of suicidal behaviour. Detection and effective treatment of continuing mood disorder, comorbid disorders and alcohol use may significantly improve clinician's ability to identify adolescent outpatients at high risk of subsequent DSH and other suicidal behaviour. Treatment interventions should aim at full recovery of depression.


Metformin treatment in young children with fragile X syndrome.
Metformin is a drug commonly used in individuals with type 2 diabetes, obesity, and impaired glucose tolerance. It has a strong safety profile in both children and adults. Studies utilizing the Drosophila model and knock out mouse model of fragile X syndrome (FXS) have found metformin to rescue memory, social novelty deficits, and neuroanatomical abnormalities. These studies provided preliminary evidence that metformin could be used as a targeted treatment for the cognitive and behavioral problems associated with FXS. Previously, a case series of children and adults with FXS treated with metformin demonstrated improvements in irritability, social responsiveness, language, and hyperactivity. Here, we present nine children with FXS between 2 and 7 years of age who were treated clinically with metformin and monitored for behavioral and metabolic changes. Parent reports and developmental testing before and after metformin are presented. There were improvements in language development and behavior (such as lethargy and stereotypy) in most of the patients. These results support the need for a controlled trial of metformin in children with FXS under 7 years old whose brains are in a critical developmental window and thus may experience a greater degree of clinical benefit from metformin.


Interrupted aortic arch: brief review and summary of an eighteen-year experience.
Interrupted aortic arch (IAA) is an uncommon congenital anomaly representing approximately 1% of congenital heart disease. More than 97% of the cases also have associated cardiac anomalies complicating their treatment. Because the median age at death in untreated cases is 10 days, this condition usually occurs as a complicated neonatal surgical emergency. There are three types of IAA: Type A is interrupted distal to the left subclavian artery. Type B, which is the most common form, is interrupted between the left common carotid and the left subclavian arteries. Type C, which is the most uncommon type, is interrupted between the innominate and left common carotid arteries. Since the first patient with this congenital anomaly was treated at our institution in 1965, 39 patients have undergone surgical treatment. Two of these (4.6%) had no associated intracardiac lesions, and both survived bypass grafting without complications. There were 12 Type A (30%), 26 Type B (67%) and one Type C (3%). A variety of individualized techniques were used to repair the defects. The three basic techniques were (1) direct aortic to aortic anastomosis bridging the gap, (2) "turndown" or "turnup" of one of the arch vessels to the aorta across the gap, or (3) bypass of the interruption with graft material. Because aortic arch and associated cardiac anomalies represent a neonatal surgical emergency, our therapeutic plan consists of treatment for biventricular failure and PGE(1) infusion to maintain ductal patency, and surgical correction as soon as feasible.


Artificial neural network for predicting pathological stage of clinically localized prostate cancer in a Taiwanese population.
We developed an artificial neural network (ANN) model to predict prostate cancer pathological staging in patients prior to when they received radical prostatectomy as this is more effective than logistic regression (LR), or combined use of age, prostate-specific antigen (PSA), body mass index (BMI), digital rectal examination (DRE), trans-rectal ultrasound (TRUS), biopsy Gleason sum, and primary biopsy Gleason grade. Our study evaluated 299 patients undergoing retro-pubic radical prostatectomy or robotic-assisted laparoscopic radical prostatectomy surgical procedures with pelvic lymph node dissection. The results were intended to predict the pathological stage of prostate cancer (T2 or T3) after radical surgery. The predictive ability of ANN was compared with LR and validation of the 2007 Partin Tables was estimated by the areas under the receiving operating characteristic curve (AUCs). Of the 299 patients we evaluated, 109 (36.45%) displayed prostate cancer with extra-capsular extension (ECE), and 190 (63.55%) displayed organ-confined disease (OCD). LR analysis showed that only PSA and BMI were statistically significant predictors of prostate cancer with capsule invasion. Overall, ANN outperformed LR significantly (0.795 ± 0.023 versus 0.746 ± 0.025, p = 0.016). Validation using the current Partin Tables for the participants of our study was assessed, and the predictive capacity of AUC for OCD was 0.695. ANN was superior to LR at predicting OCD in prostate cancer. Compared with the validation of current Partin Tables for the Taiwanese population, the ANN model resulted in larger AUCs and more accurate prediction of the pathologic stage of prostate cancer.


Genetic organization of Streptococcus salivarius 24SMBc blp-like bacteriocin locus.
In this paper, we describe, for the first time, the genetic organization of the blpU-like cassette in Streptococcus salivarius24SMBc by entire genome sequencing. This strain has recently been found useful and widely applied as an oral probiotic in the prevention of recurrent otitis media. The 24SMBc blpU-like cassette is 8,023 bp in length, organized in 11 orfs,of which orf8 encodes for the pore-forming peptide bacteriocin, belonging to class IIc, with a double-glycine leader peptide. The first characterization of blplocus was described inStreptococcus pneumoniae, showing a crucial role in interspecies competition within the nasopharynx. The salivarius blpU-like cassette is inserted upstream of the pepX gene in the chromosome. A hypervariable region between pepXand orf1 was found and used as a specific target able to distinguishS. salivarius 24SMBc from all other streptococci. All orfscarried by the blp-like cassette are functionally expressed (qPCR assays). Our results contribute to elucidate the microbial interactions in the nasopharynx, underlining the potential role of the blp locus in human nasopharyngeal colonization.


Estimating the risk of re-emergence after stopping polio vaccination.
Live vaccination against polio has effectively prevented outbreaks in most developed countries for more than 40 years, and there remain only a few countries where outbreaks of poliomyelitis by the wild strain still threaten the community. It is expected that worldwide eradication will be eventually achieved through careful surveillance and a well-managed immunization program. The present paper argues, however, that based on a simple stochastic model the risk of outbreak by a vaccine-derived strain after the cessation of vaccination is quite high, even if many years have passed since the last confirmed case. As vaccinated hosts are natural reservoirs for virulent poliovirus, the source of the risk is the vaccination itself, employed to prevent the outbreaks. The crisis after stopping vaccination will emerge when the following two conditions are met: the susceptible host density exceeds the threshold for epidemics and the vaccinated host density remains large enough to ensure the occurrence of virulent mutants in the population. Our estimates for transmission, recovery, and mutation rates, show that the probability of an outbreak of vaccine-derived virulent viruses easily exceeds 90%. Moreover, if a small fraction of hosts have a longer infectious period, as observed in individuals with innate immunodeficiency, the risk of an outbreak rises significantly. Under such conditions, successful global eradication of polio is restricted to a certain range of parameters even if inactivated polio vaccine (IPV) is extensively used after the termination of live vaccination.


Melatonin as a regulator of apoptosis in leukaemia: molecular mechanism and therapeutic perspectives.
Leukaemia is a dangerous malignancy that causes thousands of deaths every year throughout the world. The rate of morbidity and mortality is significant despite many advancements in therapy strategies for affected individuals. Most antitumour medications used now in clinical oncology use apoptotic signalling pathways to induce cancer cell death. Accumulated data have shown a direct correlation between inducing apoptosis in cancer cells with higher tumour regression and survival. Until now, the efficacy of melatonin as a powerful antitumour agent has been firmly established. A change in melatonin concentrations has been reported in multiple tumours such as endometrial, hematopoietic, and breast cancers. Findings show that melatonin's anticancer properties, such as its prooxidation function and ability to promote apoptosis, indicate the possibility of utilizing this natural substance as a promising agent in innovative cancer therapy approaches. Melatonin stimulates cell apoptosis via the regulation of many apoptosis facilitators, including mitochondria, cytochrome c, Bcl-2, production of reactive oxygen species, and apoptosis receptors. This paper aimed to further assess the anticancer effects of melatonin through the apoptotic pathway, considering the role that cellular apoptosis plays in the pathogenesis of cancer. The effect of melatonin may mean that it is appropriate for use as an adjuvant, along with other therapeutic approaches such as radiotherapy and chemotherapy.


Target size analysis by radiation inactivation of carnitine palmitoyltransferase activity and malonyl-CoA binding in outer membranes from rat liver mitochondria.
The functional molecular sizes of the protein(s) mediating the carnitine palmitoyltransferase I (CPT I) activity and the [14C]malonyl-CoA binding in purified outer-membrane preparations from rat liver mitochondria were determined by radiation-inactivation analysis. In all preparations tested the dose-dependent decay in [14C]malonyl-CoA binding was less steep than that for CPT I activity, suggesting that the protein involved in malonyl-CoA binding may be smaller than that catalysing the CPT I activity. The respective sizes computed from simultaneous analysis for molecular-size standards exposed under identical conditions were 60,000 and 83,000 DA for malonyl-CoA binding and CPT I activity respectively. In irradiated membranes the sensitivity of CPT activity to malonyl-CoA inhibition was increased, as judged by malonyl-CoA inhibition curves for the activity in control and in irradiated membranes that had received 20 Mrad radiation and in which CPT activity had decayed by 60%. Possible correlations between these data and other recent observations on the CPT system are discussed.


Combining cationic liposomal delivery with MPL-TDM for cysteine protease cocktail vaccination against Leishmania donovani: evidence for antigen synergy and protection.
With the paucity of new drugs and HIV co-infection, vaccination remains an unmet research priority to combat visceral leishmaniasis (VL) requiring strong cellular immunity. Protein vaccination often suffers from low immunogenicity and poor generation of memory T cells for long-lasting protection. Cysteine proteases (CPs) are immunogenic proteins and key mediators of cellular functions in Leishmania. Here, we evaluated the vaccine efficacies of CPs against VL, using cationic liposomes with Toll like receptor agonists for stimulating host immunity against L. donovani in a hamster model. Recombinant CPs type I (cpb), II (cpa) and III (cpc) of L. donovani were tested singly and in combination as a triple antigen cocktail for antileishmanial vaccination in hamsters. We found the antigens to be highly immunoreactive and persistent anti-CPA, anti-CPB and anti-CPC antibodies were detected in VL patients even after cure. The liposome-entrapped CPs with monophosphoryl lipid A-Trehalose dicorynomycolate (MPL-TDM) induced significantly high nitric oxide (up to 4 fold higher than controls) mediated antileishmanial activity in vitro, and resulted in strong in vivo protection. Among the three CPs, CPC emerged as the most potent vaccine candidate in combating the disease. Interestingly, a synergistic increase in protection was observed with liposomal CPA, CPB and CPC antigenic cocktail which reduced the organ parasite burden by 1013-1016 folds, and increased the disease-free survival of >80% animals at least up to 6 months post infection. Robust secretion of IFN-γ and IL-12, along with concomitant downregulation of Th2 cytokines, was observed in cocktail vaccinates, even after 3 months post infection. The present study is the first report of a comparative efficacy of leishmanial CPs and their cocktail using liposomal formulation with MPL-TDM against L. donovani. The level of protection attained has not been reported for any other subcutaneous single or polyprotein vaccination against VL.


Bioaccessibility testing of cobalt compounds.
Testing of metal compounds for solubility in artificial fluids has been used for many years to assist determining human health risk from exposure to specific compounds of concern. In lieu of obtaining bioavailability data from samples of urine, blood, or other tissues, these studies measured solubility of compounds in various artificial fluids as a surrogate for bioavailability. In this context, the measurement of metal "bioaccessibility" can be used as an in vitro substitute for measuring metal bioavailability. Bioaccessibility can be defined as a value representing the availability of metal for absorption when dissolved in in vitro surrogates of body fluids or juices. The aim of this study was to measure and compare the bioaccessibility of selected cobalt compounds in artificial human tissue fluids and human serum. A second aim was to initiate studies to experimentally validate an in vitro methodology that would provide a conservative estimate of cobalt bioavailability in the assessment of dose from human exposure to various species of cobalt compounds. This study evaluated the bioaccessibility of cobalt(II) from 11 selected cobalt compounds and an alloy in 2 physical forms in 5 surrogate human tissue fluids and human serum. Four (4) separate extraction times were used up to 72 hours. The effect of variables such as pH, dissolution time, and mass-ion effect on cobalt bioaccessibility were assessed as well. We found that the species of cobalt compound as well as the physico-chemical properties of the surrogate fluids, especially pH, had a major impact on cobalt solubility. Cobalt salts such as cobalt(II) sulfate heptahydrate were highly soluble, whereas cobalt alloys used in medical implants and cobalt aluminate spinels used as pigments, showed minimal dissolution over the period of the assay.


Spontaneous formation and nonequilibrium dynamics of a soliton-shaped Bose-Einstein condensate in a trap.
The Bose-stimulated self-organization of a quasi-two-dimensional nonequilibrium Bose-Einstein condensate in an in-plane potential is proposed. We obtained the solution of the nonlinear, driven-dissipative Gross-Pitaevskii equation for a Bose-Einstein condensate trapped in an external asymmetric parabolic potential within the method of the spectral expansion. We found that, in sharp contrast to previous observations, the condensate can spontaneously acquire a solitonlike shape for spatially homogeneous pumping. This condensate soliton performs oscillatory motion in a parabolic trap and, also, can spontaneously rotate. Stability of the condensate soliton in the spatially asymmetric trap is analyzed. In addition to the nonlinear dynamics of nonequilibrium Bose-Einstein condensates of ultracold atoms, our findings can be applied to the condensates of quantum well excitons and cavity polaritons in semiconductor heterostructure, and to the condensates of photons.


Demographic approaches to the estimation of incidence of HIV-1 infection among adults from age-specific prevalence data in stable endemic conditions.
To develop methods for estimating the incidence of HIV-1 infection among adults from age-specific prevalence data derived in stable endemic conditions. Two methods are proposed. The first method is the Cumulative Incidence and Survival Method which treats HIV-1 prevalence at any given age as the cumulative incidence of new infections at each preceding age, adjusted for mortality. A model for age-specific incidence is fitted to the data using maximum likelihood techniques. The other method is the Constant Prevalence Method whereby the incidence of new infections within a time interval (t-r, t) is calculated as the difference, after adjusting for mortality, between observed prevalence levels at two successive age intervals, whose mean ages are r years apart. The two methods were applied to data from Kampala, Uganda. Plausible estimates of age-specific and cumulative HIV-1 incidence were obtained from each of the methods. Estimates of HIV-1 incidence are sensitive to assumptions regarding the length of the survival period after infection and the stability of the epidemic. Reasonable estimates of HIV-1 incidence can be obtained from prevalence data derived in near-stable conditions. With the Constant Prevalence Method, these conditions may be relaxed if large sample sizes are available and age-reporting is good. The methods proposed could be used in the design and implementation of HIV-1 prevention trials. Cumulative incidence is a better indication of demographic impact than average age-specific incidence.


[Magnus Haaland--a pioneer in international cancer research].
Pathologist and bacteriologist Magnus Haaland (1876-1935) was a pioneer in European experimental cancer research. For eight years he worked in some of the most prominent research institutions in France, Germany and England. He worked with Elie Metschnikow and Amedée Borrel at Institut Pasteur in Paris, with Paul Ehrlich in Frankfurt am Main and with Erwin Bashford at the Imperial Cancer Research Fund in London. From 1911 to his death in 1935, he was the head of the Gade Institute in Bergen. He became a pioneer in Norwegian bacteriology research and made particular contributions to the eradication of typhoid fever in Norway. His main scientific work was on the progression of experimental transplantable tumours in mice, patterns of metastasis, and experimental hyperthermia treatment. He gave the first description of neoplastic reticuloses in mice.


A syntactic approach to seismic pattern recognition.
The nearest-neighbor decision rule for syntactic patterns is applied to seismic pattern classification. Each pattern is represented by a string. The string-to-string distance is used as a similarity measure. Another method using finite-state grammars inferred from the training samples and error-correcting parsers is also implemented. Both methods show equal recognition accuracy; however, the nearest-neighbor rule is much faster in computation speed. The classification results of real earthquake/explosion data are presented.


St George's University's Medical Student Research Institute: A Novel, Virtual Programme for Medical Research Collaboration.
Medical student research involvement has evolved to be a core component of medical education and is becoming increasingly vital to success in the United States residency match. We sought to develop a research website allowing students and research faculty to collaborate and complete projects online. The Medical Student Research Institute (MSRI) was developed by the St George's University School of Medicine in 2009 to encourage, support, facilitate and centralize medical student research. There are 63 active students in the MSRI (22 students in basic science and 41 students in clinical rotations). The mean GPA for basic science student members was 3.81 ± 0.27 and was 3.80 ± 0.20 for clinical student members. The mean United States Medical Licensing Examination (USMLE) Step 1 score was 241.6 ± 17.5. Since 2009, MSRI students have published 87 manuscripts in 33 different journals and have presented at 14 different national and international conferences. A web-based MSRI provides a virtual, entirely online resource for coordinating remote research collaboration between medical students and faculty whose opportunities would be otherwise limited. Initial experiences with the programme have been positive and the framework and concept of the MSRI provides a platform for university and medical schools to provide research opportunities to students who may not have face-to-face access to research faculty.


Genomic diversity in Campylobacter jejuni: identification of C. jejuni 81-176-specific genes.
Since the publication of the complete genomic sequence of Campylobacter jejuni NCTC 11168 in February 2000, evidence has been compiling that suggests C. jejuni strains exhibit high genomic diversity. In order to investigate this diversity, the unique genomic DNA sequences from a nonsequenced Campylobacter strain, C. jejuni 81-176, were identified by comparison with C. jejuni NCTC 11168 by using a shotgun DNA microarray approach. Up to 63 kb of new chromosomal DNA sequences unique to this pathogen were obtained. Eighty-six open reading frames were identified by the presence of uninterrupted coding regions encoding a minimum of 40 amino acids. In addition, this study shows that the whole-plasmid shotgun microarray approach is effective and provides a comprehensive coverage of DNA regions that differ between two closely related genomes. The two plasmids harbored by this Campylobacter strain, pTet and pVir, were also sequenced, with coverages of 2.5- and 2.9-fold, respectively, representing 72 and 92% of their complete nucleotide sequences. The unique chromosomal genes encode proteins involved in capsule and lipooligosaccharide biosynthesis, restriction and modification systems, and respiratory metabolism. Several of these unique genes are likely associated with C. jejuni 81-176 fitness and virulence. Interestingly, the comparison of C. jejuni 81-176 unique genes with those of C. jejuni ATCC 43431 revealed a single gene which encodes a probable TraG-like protein. The product of this gene might be associated with the mechanism of C. jejuni invasion into epithelial cells. In conclusion, this study extends the repertoire of C. jejuni genes and thus will permit the construction of a composite and more comprehensive microarray of C. jejuni.


Prevalence of cigarette smoking among adult population in eastern Poland.
Cigarette smoking is the strongest modifiable factor, which shortens the life span and deteriorates the quality of life. It increases the risk of development of cancer, cardiovascular and respiratory system diseases. The objective of the study was evaluation of the prevalence of cigarette smoking among the adult population of the Lublin Region, and investigation of the relationship between nicotinism and respondents? place of residence, and other selected socio-economic factors. Data concerning the cigarette smoking habit was obtained from 3,993 people - 2,447 females and 1,546 males; 23.0 percent of respondents in the study were smokers - 35.6 percent of males and 15.1 percent of females. The percentage of male smokers was similar in rural and urban areas. Urban females were smokers more often than those living in rural areas. A decrease was noted in the difference which has been observed to-date between the percentage of urban and rural female smokers. The highest percentage of smokers occurred among the population aged 41-50, while the lowest - among the youngest and the oldest respondents. The percentage of smoking farmers was lower than that of respondents performing non-agricultural occupations, also among rural inhabitants. Those who were occupationally active were smokers more frequently than those not engaged in occupational activity. The lowest percentage of smokers was noted among respondents who had the highest education level, while the highest percentage was observed among those who had vocational education.


Conversion of Laparoscopic Roux en Y Gastric Bypass (RYGB) to Single Anastomosis Duodenal Switch (SADS).
The surgical management of weight regain following RYGB remains controversial. Simpler modifications such as endoscopic suturing and banding the bypass have had variable efficacy. Distalization of the bypass has resulted in a high risk of malabsorption-related complications as reported by Amor et al. (Obes Surg. 27(1):273-274, 2017); Borbély et al. (Obes Surg. 27(2):439-444, 2017); Thomopoulos et al. (Surg Laparosc Endosc Percutan Tech. 0(0):1, 2018); and Tran et al. (Obes Surg. 26(7):1627-1634, 2016). Conversion to a procedure such as duodenal switch (DS) or SADS with greater average weight loss would be logical but is technically challenging and is related to a high complication rate especially with the reformation of the stomach. In this video, we present the technique that we have adapted to make this complex case reproducible minimizing operative risk. A 49-year-old female weighing 154 kg (BMI 57 kg/m2) with sleep apnea disease underwent a laparoscopic RYGB in 2009. She had an initial weight loss of 47 kg but had complete recidivism with a weight of 151 kg (BMI 56 kg/m2). Upper gastrointestinal (barium swallow study) and esophagogastroduodenoscopy showed no evidence of fistula, with a normal pouch diameter and length with stoma size of 2 cm. Blood test showed no significant micro/macronutrient deficiencies. With super morbid obesity refractory to RYGB, it was our belief that conversion to SADS was the best alternative. We introduced a subcostal camera trocar with Optiview and we observed epiploic adherences to the previous anastomosis. We placed an additional trocar to remove adhesions in the re-operative field. We measured the 300 cm of the small bowel proximal to the ileocecal valve. We next divided the antecolic Roux limb from the gastric remnant preserving the left gastric artery and divided the pouch proximal to the gastrojejunal anastomosis. We identified and mobilized the remnant stomach preserving the 8 lowest branches of the right gastroepiploic artery. After reaching the angle of His, we were able to separate the remnant and the pouch. The pouch was reshaped using a 42Fr bougie for guidance. A gastrostomy was made and a matching opening was created near the lesser curvature on the remnant. We then began gastrogastric anastomosis. First, the posterior layer was done and then the bougie was placed through into the remnant. The sleeve and fundic resection was done. The bougie was replaced by an oral gastric tube and the anterior layer of the anastomosis completed. This was tested with methylene blue. We next divided the duodenum postpylorus, preserving the right gastric artery. We performed and tested a hand-sewn duodeno-ileal anastomosis with a common limb length of 300 cm. There were no intra- or postoperative complications and the patient was discharged after 2 days. We believe that this video shows a reproducible technique for this complex anastomosis. Preservation of the distal epiploics makes the gastro-gastric anastomosis safer but requires direct dissection of the duodenum.


Splint: the efficacy of orthotic management in rest to prevent equinus in children with cerebral palsy, a randomised controlled trial.
Range of motion deficits of the lower extremity occur in about the half of the children with spastic cerebral palsy (CP). Over time, these impairments can cause joint deformities and deviations in the children's gait pattern, leading to limitations in moblity. Preventing a loss of range of motion is important in order to reduce secondary activity limitations and joint deformities. Sustained muscle stretch, imposed by orthotic management in rest, might be an effective method of preventing a decrease in range of motion. However, no controlled study has been performed. A single blind randomised controlled trial will be performed in 66 children with spastic CP, divided over three groups with each 22 participants. Two groups will be treated for 1 year with orthoses to prevent a decrease in range of motion in the ankle (either with static or dynamic knee-ankle-foot-orthoses) and a third group will be included as a control group and will receive usual care (physical therapy, manual stretching). Measurements will be performed at baseline and at 3, 6, 9 and 12 months after treatment allocation. The primary outcome measure will be ankle dorsiflexion at full knee extension, measured with a custom designed hand held dynamometer. Secondary outcome measures will be i) ankle and knee flexion during gait and ii) gross motor function. Furthermore, to gain more insight in the working mechanism of the orthotic management in rest, morphological parameters like achilles tendon length, muscle belly length, muscle fascicle length, muscle physiological cross sectional area length and fascicle pennation angle will be measured in a subgroup of 18 participants using a 3D imaging technique. This randomised controlled trial will provide more insight into the efficacy of orthotic management in rest and the working mechanisms behind this treatment. The results of this study could lead to improved treatments. Nederlands Trial Register NTR2091.


Type IV secretion: intercellular transfer of macromolecules by systems ancestrally related to conjugation machines.
Bacterial conjugation systems are highly promiscuous macromolecular transfer systems that impact human health significantly. In clinical settings, conjugation is exceptionally problematic, leading to the rapid dissemination of antibiotic resistance genes and other virulence traits among bacterial populations. Recent work has shown that several pathogens of plants and mammals - Agrobacterium tumefaciens, Bordetella pertussis, Helicobacter pylori and Legionella pneumophila - have evolved secretion pathways ancestrally related to conjugation systems for the purpose of delivering effector molecules to eukaryotic target cells. Each of these systems exports distinct DNA or protein substrates to effect a myriad of changes in host cell physiology during infection. Collectively, secretion pathways ancestrally related to bacterial conjugation systems are now referred to as the type IV secretion family. The list of putative type IV family members is increasing rapidly, suggesting that macromolecular transfer by these systems is a widespread phenomenon in nature.


Balanced Options for Access and Benefit-Sharing: Stakeholder Insights on Provider Country Legislation.
The over-arching aim of the access and benefit-sharing (ABS) of genetic resources is to enable fair distribution of benefits between the users (such as universities and biotech companies) and providers (such as biodiversity rich countries) so as to both open the doors for innovation and create incentives for biodiversity conservation. Access to genetic resources is crucial for research related to conservation of plant genetic resources as well as R&D for agricultural products and evolved crops that can attain to the new weather conditions climate change brings. Therefore, access to genetic resources in general as well as benefit-sharing from that access is a key element for sustainable development in order to secure research as well as environmental sustainability and resource availability. ABS is currently a rapidly developing and evolving field that is shaped by each and every implementation of the Parties. This means that the national implementation of the Parties determine how ABS goals are realised and how ABS principles find form within regulatory mechanisms. These principles are found in international legal documents such as the Convention on Biological Diversity (CBD) as well as Nagoya Protocol. Additionally, decisions and guidelines drafted by the Conference of the Parties to the Convention on Biological Diversity shape these principles that are then to be fulfilled by the Parties when drafting their ABS laws by means of implementing regulatory mechanisms that comply with the international law. This article reviews 20 provider country's ABS frameworks as well as one regional law with the aim of identifying the common regulatory mechanisms that find place in these legal texts. This descriptive approach is then followed by an empirical comparative analysis through semi-structured stakeholder interviews in order to identify the most beneficial regulatory mechanisms according to ABS experts that belong in four different stakeholder groups (provider countries, academic users, industrial users and collections).


Long-term response after stopping tenofovir disoproxil fumarate in non-cirrhotic HBeAg-negative patients - FINITE study.
There is currently no virological cure for chronic hepatitis B but successful nucleos(t)ide analogue (NA) therapy can suppress hepatitis B virus (HBV) DNA replication and, in some cases, result in HBsAg loss. Stopping NA therapy often leads to viral relapse and therefore life-long therapy is usually required. This study investigated the potential to discontinue tenofovir disoproxil fumarate (TDF) therapy in HBeAg-negative patients. Non-cirrhotic HBeAg-negative patients who had received TDF for ≥4years, with suppressed HBV DNA for ≥3.5years, were randomly assigned to either stop (n=21) or continue (n=21) TDF monotherapy. Standard laboratory tests including HBV DNA viral load, HBsAg and alanine aminotransferase (ALT) measurements, and adverse event reporting were carried out during treatment and post-treatment follow-up for 144weeks. Of the patients who stopped TDF therapy, 62% (n=13) remained off-therapy to Week 144. Median HBsAg change in this group was -0.59log10IU/ml (range -4.49 to 0.02log10IU/ml) vs. 0.21log10IU/ml in patients who continued TDF therapy. Four patients (19%) achieved HBsAg loss. Patients stopping therapy had initial fluctuations in viral load and ALT; however, at Week 144, 43% (n=9) had either achieved HBsAg loss or had HBV DNA <2,000IU/ml. There were no unexpected safety issues identified with stopping TDF therapy. This controlled study demonstrated the potential for HBsAg loss and/or sustained virological response in non-cirrhotic HBeAg-negative patients stopping long-term TDF therapy. Lay summary: Nucleos(t)ide analogue (NA) is usually a life-long therapy for HBV patients. This randomised controlled study investigated the discontinuation of tenofovir disoproxil fumarate (TDF) therapy in HBeAg-negative patients. Of the patients who stopped TDF therapy, 62% remained off-therapy to Week 144, of which 43% of patients had achieved either HBsAg loss or HBV DNA <2,000IU/ml. This offers a potential for long-term HBV-suppressed patients without cirrhosis to stop NA therapy under strict surveillance. Clinical trial number: NCT01320943.


Glucocorticoid Receptor ChIP-Seq Identifies PLCD1 as a KLF15 Target that Represses Airway Smooth Muscle Hypertrophy.
Glucocorticoids exert important therapeutic effects on airway smooth muscle (ASM), yet few direct targets of glucocorticoid signaling in ASM have been definitively identified. Here, we show that the transcription factor, Krüppel-like factor 15 (KLF15), is directly induced by glucocorticoids in primary human ASM, and that KLF15 represses ASM hypertrophy. We integrated transcriptome data from KLF15 overexpression with genome-wide analysis of RNA polymerase (RNAP) II and glucocorticoid receptor (GR) occupancy to identify phospholipase C delta 1 as both a KLF15-regulated gene and a novel repressor of ASM hypertrophy. Our chromatin immunoprecipitation sequencing data also allowed us to establish numerous direct transcriptional targets of GR in ASM. Genes with inducible GR occupancy and putative antiinflammatory properties included IRS2, APPL2, RAMP1, and MFGE8. Surprisingly, we also observed GR occupancy in the absence of supplemental ligand, including robust GR binding peaks within the IL11 and LIF loci. Detection of antibody-GR complexes at these areas was abrogated by dexamethasone treatment in association with reduced RNA polymerase II occupancy, suggesting that noncanonical pathways contribute to cytokine repression by glucocorticoids in ASM. Through defining GR interactions with chromatin on a genome-wide basis in ASM, our data also provide an important resource for future studies of GR in this therapeutically relevant cell type.


The effect of albumin dialysis on cytokine levels in acute liver failure and need for liver transplantation.
In acute liver failure (ALF), detoxification capacity of liver cells is reduced and a variety of cytokines, immune modulators, and toxic substances are accumulating. Multiple organ failure in ALF has been associated with increased blood cytokine levels. We have used a blood purification system, molecular adsorbent recirculating system (MARS), which is based on removal of both protein bound and water-soluble substances and toxins in liver failure. In this study, we measured the effect of MARS therapy on plasma cytokine levels in 49 patients with ALF. Interleukin 6 (IL-6), IL-8, IL-10 and tumor necrosis factor (TNF)alfa were determined immediately before and after the first MARS therapy and after the last session using enzyme-linked immunosorbent assays. The overall survival of these ALF patients was 82% at 6 months; the native liver recovered in 26 cases, and 14 were successfully transplanted. All three interleukins were increased before the MARS treatment but only anti-inflammatory IL-10 was reduced significantly during therapy, which in this setting could be interpreted as a positive effect. We were not able to show constant decreases in proinflammatory cytokines, but only transient effects on IL-8 and IL-6. Surprisingly TNFalfa level was normal and did not change during therapy. In theory, MARS albumin dialysis may remove toxic substances from the blood circulation and thereby improve the possibilities of the liver to recover; however, of the measured cytokines only IL-10 decreased significantly.


Integrating donor conception into identity development: adolescents in fatherless families.
To study the processes by which donor-conceived children incorporate donor conception into their subjective sense of identity. Cross-sectional. Family homes. Nineteen donor-conceived adolescents. Administration of an interview and questionnaire. The mother-child relationship was assessed through the Friends and Family Interview, a semistructured interview designed to assess adolescents' security of attachment in terms of secure-autonomous, insecure-dismissive, insecure-preoccupied, and insecure-disorganized attachment patterns. The Donor Conception Identity Questionnaire assessed adolescents' thoughts and feelings about donor conception, yielding two factors: [1] curiosity about donor conception and [2] avoidance of donor conception. Statistically significant associations were found between the Curiosity scale and the secure-autonomous and insecure-dismissing attachment ratings. Adolescents with secure-autonomous attachment patterns were more interested in exploring donor conception whereas those with insecure-dismissing patterns were less likely to express curiosity. Insecure-disorganized attachment ratings were statistically significantly correlated with the Avoidance scale, indicating higher levels of negative feelings about donor conception. The results of this study of the influence of parent-child relationships on thoughts and feelings about donor conception in adolescence suggest that the valence of the parent-child relationship influences adolescents' appraisal of their donor conception within the context of their growing sense of identity.


Clinical Presentation, Predictors, and Outcomes Among Mineralocorticoid Receptor Antagonist (MRA)-Eligible Acute Heart Failure Patients in the Heart Function Assessment Registry Trial in Saudi Arabia (HEARTS).
Mineralocorticoid receptor antagonist (MRA) therapy is indicated after myocardial infarction in patients with acute heart failure (AHF) with an ejection fraction ≤40% and lacking contraindications. We analyzed clinical presentations, predictors, and outcomes of MRA-eligible patients within a prospective registry of patients with AHF from 18 hospitals in Saudi Arabia, from 2009 to 2010. For this subgroup, mortality rates were followed until 2013, and the clinical characteristics, management, predictors, and outcomes were compared between MRA-treated and non-MRA-treated patients. Of 2609 patients with AHF, 387 (14.8%) were MRA eligible, of which 146 (37.7%) were prescribed MRAs. Compared with non-MRA-treated patients, those prescribed MRAs more commonly exhibited non-ST-segment elevation myocardial infarction, acute on chronic heart failure, past history of ischemic heart disease, and severe left ventricular systolic dysfunction; were more commonly administered oral furosemide and digoxin; and had higher in-hospital recurrent congestive HF rates. Mortality did not significantly differ ( P > .05) between groups. In Saudi Arabia, 37.7% of eligible patients received MRA treatment, which is higher than that in developed countries. The lack of long-term survival benefit raises concerns about systematic problems, for example, proper follow-up and management after hospital discharge, warranting further investigation.


Silica Urinary Stones: A Case Report and A Brief Review of Literature.
Silicate stones are extraordinarily rare in human beings, but when present, they are often associated with ingestion of Magnesium Trisilicate, an antacid medication. However, there have been few case reports of patients who developed silicate stones, without ingestion of Magnesium Trisilicate. Hereby, we present the case of a 67-year-old man who developed acute kidney injury due to obstructive uropathy, detected during his scheduled chemotherapy for his relapsing multiple myeloma. Abdominal ultrasound and CT scan imaging demonstrated multiple non-mobile calcifications in the bladder neck/prostate bed. Stone analysis showed a material resembling silica. This case with silicate urinary tract stone highlights this extra-rare urinary stone in a patient without any identified source of silicate. DOI: 10.52547/ijkd.7044.


Smoothened receptor signaling regulates the developmental shift of GABA polarity in rat somatosensory cortex.
Sonic hedgehog (Shh) and its patched-smoothened receptor complex control a variety of functions in the developing central nervous system, such as neural cell proliferation and differentiation. Recently, Shh signaling components have been found to be expressed at the synaptic level in the postnatal brain, suggesting a potential role in the regulation of synaptic transmission. Using in utero electroporation of constitutively active and negative-phenotype forms of the Shh signal transducer smoothened (Smo), we studied the role of Smo signaling in the development and maturation of GABAergic transmission in the somatosensory cortex. Our results show that enhancing Smo activity during development accelerates the shift from depolarizing to hyperpolarizing GABA in a manner dependent on functional expression of potassium-chloride cotransporter type 2 (KCC2, also known as SLC12A5). On the other hand, blocking Smo activity maintains the GABA response in a depolarizing state in mature cortical neurons, resulting in altered chloride homeostasis and increased seizure susceptibility. This study reveals unexpected functions of Smo signaling in the regulation of chloride homeostasis, through control of KCC2 cell-surface stability, and the timing of the GABA excitatory-to-inhibitory shift in brain maturation.


Functional impacts of non-coding RNA processing on enhancer activity and target gene expression.
Tight regulation of gene expression is orchestrated by enhancers. Through recent research advancements, it is becoming clear that enhancers are not solely distal regulatory elements harboring transcription factor binding sites and decorated with specific histone marks, but they rather display signatures of active transcription, showing distinct degrees of transcription unit organization. Thereby, a substantial fraction of enhancers give rise to different species of non-coding RNA transcripts with an unprecedented range of potential functions. In this review, we bring together data from recent studies indicating that non-coding RNA transcription from active enhancers, as well as enhancer-produced long non-coding RNA transcripts, may modulate or define the functional regulatory potential of the cognate enhancer. In addition, we summarize supporting evidence that RNA processing of the enhancer-associated long non-coding RNA transcripts may constitute an additional layer of regulation of enhancer activity, which contributes to the control and final outcome of enhancer-targeted gene expression.


Risk controlled decision trees and random forests for precision Medicine.
Statistical methods generating individualized treatment rules (ITRs) often focus on maximizing expected benefit, but these rules may expose patients to excess risk. For instance, aggressive treatment of type 2 diabetes (T2D) with insulin therapies may result in an ITR which controls blood glucose levels but increases rates of hypoglycemia, diminishing the appeal of the ITR. This work proposes two methods to identify risk-controlled ITRs (rcITR), a class of ITR which maximizes a benefit while controlling risk at a prespecified threshold. A novel penalized recursive partitioning algorithm is developed which optimizes an unconstrained, penalized value function. The final rule is a risk-controlled decision tree (rcDT) that is easily interpretable. A natural extension of the rcDT model, risk controlled random forests (rcRF), is also proposed. Simulation studies demonstrate the robustness of rcRF modeling. Three variable importance measures are proposed to further guide clinical decision-making. Both rcDT and rcRF procedures can be applied to data from randomized controlled trials or observational studies. An extensive simulation study interrogates the performance of the proposed methods. A data analysis of the DURABLE diabetes trial in which two therapeutics were compared is additionally presented. An R package implements the proposed methods ( https://github.com/kdoub5ha/rcITR).


Physiocochemical characterization of mouse myeloma proteins: demonstration of heterogeneity for each myeloma globulin.
Physicochemical characterization of mouse myeloma proteins revealed the individuality of each myeloma protein. When the myeloma proteins are considered collectively a wide range of individual properties were represented, including electrophoretic mobilities varying from the gamma to alpha region, hexose contents from 1 to 4 per cent, and ultracentrifugal components from 6.5 to 13 S. The 20 myeloma proteins could be divided into groups, the gamma type and the beta type myeloma globulins, on the basis of physicochemical, as well as immunoelectrophoretic, studies. Two gamma type myeloma proteins (5563, MPC-11) resembled normal gamma globulins, sedimenting as a single 6.5 S peak in the ultracentrifuge, and having a relatively low hexose content (1 per cent). Eighteen beta type mouse myeloma proteins differed from gamma myeloma proteins and, typically, were found on ultracentrifugal analysis to have multiple components with sedimentation coefficients of 6.5, 9, 11, and 13 S, having a higher hexose content (2 to 4 per cent) as well as distinctive chromatographic and starch gel electrophoretic properties. All of the mouse myeloma proteins were heterogeneous and heterogeneity of two types was observed. Polymer formation was responsible for the 9, 11, and/or 13 S components seen on ultracentrifugation of the beta type myeloma proteins. Starch gel electrophoresis revealed this type of heterogeneity as relatively widely separated myeloma protein components, presumably owing to the retardation effect of starch gel on the electrophoretic migration of the larger polymers. Starch gel electrophoresis revealed a different type of heterogeneity for the two gamma type myeloma proteins, each of these being shown to contain 5 or more components differing only in electrophoretic properties. The physicochemical characteristics of the gamma-type and beta-type myeloma proteins in the mouse indicated the close similarity of these proteins to the gamma- and beta-(2A)-myeloma proteins in man.


Balance between the CMC/ACP Nanocomplex and Blood Assimilation Orchestrates Immunomodulation of the Biomineralized Collagen Matrix.
Calcium phosphate-based biomineralized biomaterials have broad application prospects. However, the immune response and foreign body reactions elicited by biomineralized materials have drawn substantial attention recently, contrary to the immune microenvironment optimization concept. Therefore, it is important to clarify the immunomodulation properties of biomineralized materials. Herein, we prepared the biomineralized collagen matrix (BCM) and screened the key immunomodulation factor carboxymethyl chitosan/amorphous calcium phosphate (CMC/ACP) nanocomplex. The immunomodulation effect of the BCM was investigated in vitro and in vivo. The BCM triggered evident inflammatory responses and cascade foreign body reactions by releasing the CMC/ACP nanocomplex, which activated the potential TLR4-MAPK/NF-κB pathway, compromising the collagen matrix biocompatibility. By contrast, blocking the CMC/ACP nanocomplex release via the blood assimilation process of the BCM mitigated the inflammation and foreign body reactions, enhancing biocompatibility. Hence, the immunomodulation of the BCM was orchestrated by the balance between the CMC/ACP nanocomplex and the blood assimilation process. Controlling the release of the CMC/ACP nanocomplex to accord the biological effects of ACP with the temporal regenerative demands is key to developing advanced biomineralized materials.


Meta-analysis of primary care delivered buprenorphine treatment retention outcomes.
Background: Currently, the capacity to provide buprenorphine treatment (BT) is not sufficient to treat the growing number of people in the United States with opioid use disorder (OUD). We sought to examine participant retention in care rates of primary care delivered BT programs and to describe factors associated with retention/attrition for participants receiving BT in this setting.Objectives: A PRISMA-guided search of various databases was performed to identify the articles focusing on efficacy of BT treatment and OUD.Method: A systematic literature search identified 15 studies examining retention in care in the primary care setting between 2002 and 2020. Random effects meta-regression were used to identify retention rates across studies.Results: Retention rates decreased across time with a mean 0.52 rate at one year. Several factors were found to be related to retention, including: race, use of other drugs, receipt of counseling, and previous treatment with buprenorphine.Conclusions: While we only investigate BT through primary care, our findings indicate retention rates are equivalent to the rates reported in the specialty care literature. More work is needed to examine factors that may impact primary care delivered BT specifically and differentiate participants that may benefit from care delivered in specialty over primary care as well as the converse.


Management and outcomes of lower risk patients presenting with acute coronary syndromes in a multinational observational registry.
To document patterns of risk stratification, management practices, and outcomes among patients with acute coronary syndromes (ACS) presenting without high risk features. The study was based on 11,885 consecutive patients presenting with non-ST segment elevation ACS enrolled in GRACE (global registry of acute coronary events). Patients without dynamic ST segment changes, positive troponin (or other cardiac markers), or haemodynamic or arrhythmic instability were defined as being at lower risk. Management and outcomes were compared with high risk presentations. Of 11,885 patients presenting with unstable angina or non-ST segment elevation myocardial infarction, 4252 (36%) were regarded as being at lower risk. Functional testing for risk stratification was performed in 1163 of 4207 (28%) lower risk and 1531 of 7521 (20%) high risk patients (p < 0.0001). Coronary angiography was performed in 1930 of 4190 (46%) and 3860 of 7544 (51%), and echocardiography in 1692 of 4190 (40%) and 4348 of 7533 (58%) of lower risk and high risk patients, respectively (p < 0.0001 for both). Over one third of patients did not undergo further risk assessment with angiography or functional testing (2746 of 7437 (37%) high risk, 1499 of 4148 (36%) lower risk, not significant). Death occurring in hospital was more likely in the high risk cohort (41 of 4227 (1.0%) lower risk v 215 of 7586 (2.8%) high risk, p < 0.0001), whereas rates of recurrent angina during admission and readmission were similar in both groups (1354 of 4231 (32%) high risk, 2313 of 7587 (31%) lower risk, not significant). In the six months after discharge, death or myocardial infarction occurred in 79 of 3223 (2.5%) lower risk patients and 302 of 5451 (5.5%) high risk patients (p < 0.0001). Globally, further risk stratification after ACS presentation is suboptimal, regardless of presenting characteristics. Although in-hospital death and myocardial infarction are uncommon, recurrent ischaemia is encountered often in both groups. It remains to be seen whether better outcomes may be achieved with wider application of risk stratification and appropriately directed management strategies.


George Lyman Duff Memorial Lecture. Lifestyles, major risk factors, proof and public policy.
In this report major risk factors in coronary heart disease (CHD) are reviewed, with particular emphasis on the role of nutrition. International and national epidemiologic data indicate that reducing or eliminating certain risk factors (e.g., a diet high in cholesterol and saturated fats) may reduce the risk of premature CHD. Most trends indicate that many Americans are more concerned about diet for health reasons. Preventive measures for CHD are also discussed.


Two new species of Halysioncum Caira, Marques, Jensen, Kuchta et Ivanov, 2013 (Cestoda, Diphyllidea) from Indo-Pacific rays of the genus Aetomylaeus Garman (Myliobatiformes, Myliobatidae).
Recent collections of cestode parasites from two species of the myliobatid genus Aetomylaeus Garman from several localities in the Pacific Ocean resulted in the discovery of two new species of Halysioncum Caira, Marques, Jensen, Kuchta et Ivanov, 2013. Halysioncum gibsoni sp. n. from Aetomylaeus maculatus (Gray) in the South China Sea off Borneo differs from all of its congeners in having the following combination of characters: 27 apical hooks (14 type A and 13 type B hooks), 11-12 lateral hooklets, 22-28 spines per column on the cephalic peduncle, testes distributed in a single column and an internal seminal vesicle. Halysioncum arafurense sp. n., recovered from Aetomylaeus cf. nichofii 2 (sensu Naylor et al. 2012b) in the Arafura Sea off the Wessel Islands, Northern Territory, Australia, can be distinguished from its congeners based on the following combination of characters: 23 apical hooks (12 type A and 11 type B hooks), the number of lateral hooklets (9-11), the number of spines per column on the cephalic peduncle (20-24), the number and distribution of the testes (13-15 testes in two irregular columns), and the distribution of vitelline follicles (interrupted dorsally at the level of the ovarian lobes). Both species represent the first verified records of diphyllideans from eagle rays of the genus Aetomylaeus and formally extend the host associations of diphyllideans to include a third genus of Myliobatiformes. The myliobatiforms are indeed an understudied group of available hosts for diphyllideans and represent interesting target hosts if the diversity of diphyllidean tapeworms is to be fully estimated and understood.


Cloning and characterization of CalS7 from Micromonospora echinospora sp. calichensis as a glucose-1-phosphate nucleotidyltransferase.
The deoxysugar biosynthetic gene cluster of calicheamicin contains the calS7, which encodes glucose-1-phosphate nucleotidyltransferase and converts glucose-1-phosphate and nucleotides (NTP) to NDP-glucose and pyrophosphate. calS7 was expressed in Escherichia coli BL21(DE3), and the purified protein had significant thymidylyltransferase and uridylyltransferase activities as well, with some guanidylyltransferase activity but negligible cytidyl and adenyltransferase activity. The functions of thymidylyltransferase and uridylyltransferase were also verified using one-pot enzymatic synthesis of TMK and ACK. The products were analyzed by HPLC and ESI/MS, which showed peaks at m/z = 563 and 565 for TDP-D: -glucose and UDP-D-glucose, respectively, in negative mode.


Adaptogenic potential of curcumin in experimental chronic stress and chronic unpredictable stress-induced memory deficits and alterations in functional homeostasis.
The present study was designed to investigate the role of curcumin in chronic stress and chronic unpredictable stress-induced memory deficits and alteration of functional homeostasis in mice. Chronic stress was induced by immobilizing the animal for 2 h daily for 10 days, whereas chronic unpredictable stress was induced by employing a battery of stressors of variable magnitude and time for 10 days. Curcumin was administered to drug-treated mice prior to induction of stress. Body weight, adrenal gland weight, ulcer index and biochemical levels of glucose, creatine kinase, cholesterol, corticosterone, thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) were evaluated to assess stress-induced functional changes. Memory deficits were evaluated using the elevated plus maze (EPM) model. Chronic stress and chronic unpredictable stress significantly increased the levels of corticosterone, glucose and creatine kinase and decreased cholesterol levels. Moreover, chronic stress and chronic unpredictable stress resulted in severe memory deficits along with adrenal hypertrophy, weight loss and gastric ulceration. Chronic stress and chronic unpredictable stress also increased oxidative stress assessed in terms of increase in TBARS and decrease in GSH levels. Pretreatment with curcumin (25 and 50 mg/kg p.o.) attenuated chronic stress and chronic unpredictable stress-associated memory deficits, biochemical alterations, pathological outcomes and oxidative stress. It may be concluded that curcumin-mediated antioxidant actions and decrease in corticosterone secretion are responsible for its adaptogenic and memory restorative actions in chronic and chronic unpredictable stress.


Optimal nutrition: fibre and phytochemicals.
There is currently intense research interest in secondary plant metabolites because of their potential preventative effects on the chronic diseases of Western societies, especially cardiovascular disease and cancer. To date most of the research has focused on the identification of plant-derived substances and their potential protective effects against specific chronic diseases. The important issue of determining the optimal intake of those substances, such that the beneficial effects are maximized without manifestation of adverse effects, has yet to be addressed in most cases. Furthermore, there are no specific functional markers that can be used to assess optimal intake, although it may be possible to use biomarkers such as serum cholesterol if the rest of the diet is strictly controlled. The present review discusses a wide range of substances associated with plants, including dietary fibre, resistant starch, oligosaccharides, phyto-oestrogens, phytosterols, flavonoids, terpenes and isothiocyanates, and attempts where possible to indicate optimal intakes and to suggest functional markers.


Developmental alteration of hepatic UDP-glucuronosyltransferase and sulphotransferase towards androsterone and 4-nitrophenol in Wistar rats.
Postnatal development of hepatic UDP-glucuronosyltransferase and sulphotransferase activities towards androsterone and 4-nitrophenol as well as cytochrome P-450 contents was studied in male and female Wistar rats. The rats with high and low UDP-glucuronosyltransferase activity towards androsterone were classified by the genotype of the parent animals. UDP-glucuronosyltransferase activity towards androsterone began rapidly to enhance after 30 days of age in the high-activity group, whereas the transferase activity remained low throughout in the low-activity group. Such a striking difference was not observed in UDP-glucuronosyltransferase activity towards 4-nitrophenol, sulphotransferase activity towards androsterone and 4-nitrophenol, and cytochrome P-450 contents. Sex-based difference in the sulphotransferase activity was marked after 30 days of age. Sulphotransferase activity towards androsterone was much higher in adult females than in adult males, whereas higher sulphation activity towards 4-nitrophenol was found in adult males. The results also indicate that the low level of the UDP-glucuronosyltransferase activity did not lead to compensatory stimulation of the sulphotransferase activity.


Exploring Novel Biologically-Relevant Chemical Space Through Artificial Intelligence: The NCATS ASPIRE Program.
In recent years, artificial intelligence (AI)/machine learning (ML; a subset of AI) have become increasingly important to the biomedical research community. These technologies, coupled to big data and cheminformatics, have tremendous potential to improve the design of novel therapeutics and to provide safe and effective drugs to patients. A National Center for Advancing Translational Sciences (NCATS) program called A Specialized Platform for Innovative Research Exploration (ASPIRE) leverages advances in AI/ML, automated synthetic chemistry, and high-throughput biology, and seeks to enable translation and drug development by catalyzing exploration of biologically active chemical space. Here we discuss the opportunities and challenges surrounding the application of AI/ML to the exploration of novel biologically relevant chemical space as part of ASPIRE.


[Medical rehabilitation in nursing home--effects on functional outcome and use of the services].
Improved functioning is a primary objective in nursing homes. A total of 146 patients participated in the study, 116 for rehabilitation and 30 for respite care. 122 were admitted from home, 23 from hospital and one from a full-time care facility. The mean age was 78. The multi-disciplinary team consisted of a geriatrician, registered nurses and auxiliary nurses, an occupational therapist, a physical therapist and a speech therapist. Assessments were made before admission and about two months after discharge. The mean number of days in the nursing home was 35 (28-42 days). A total of 141 were able to resume living at home, whereas five were discharged to permanent care in a nursing home. At the follow-up, gait was improved for 23, was unchanged for 121, and had deteriorated in two (p < 0.001). Of the 21 patients who had been confined to wheelchairs or were bedridden, eight were now able to walk. Regarding change in ADL functions, only personal hygiene reached statistical significance (p < 0.05). Perceived global coping was improved for rehabilitation patients (p = 0.05). No significant changes in mental functioning or in the use of nursing services were found. The average number of hours of home help was reduced from 3.3 to 2.7 a week (p = 0.01). The most notable effects were improved mobility and decreased dependence on home-help services.