Understanding acute apophyseal spinous process avulsion injuries.
Apophyseal spinous process avulsion injury was first described in 1941. Since then, there have been sparse additional reports in the literature. The authors report their second case, involving an elite adolescent tennis player. The patient underwent surgical excision of the avulsed spinous process 12 weeks after initial presentation and experienced complete resolution of back pain. The authors provide the first reported histopathological analysis of the avulsion fracture site in the literature for both of their cases. The avulsion injury of the interspinous ligament was characterized by hypercellular fibrocartilage tissue, similar to that seen in severe Osgood-Schlatter's disease. The key physical examination finding in patients with avulsion spinous process fractures is acute tenderness directly over the fracture site that worsens with flexion rather than extension (unlike in spondylolysis). Patients should have routine radiographs, including dynamic flexion-extension views, magnetic resonance imaging, and computed tomography. The authors conclude that after 6 months of nonsurgical management for an athlete, surgical excision should be offered as an alternative. In both of their cases, nonsurgical management failed. Surgical excision offers definitive and simple treatment, as well as early return to athletic activities. Both patients were allowed to return to their competitive level of performance 6 weeks after surgery.


[Resistance to the inhibitory effect of dexamethasone in brain tumor patients].
Out of 24 patients with brain tumors, 22 proved to be resistant to inhibition by dexamethasone. There were no significant differences in the sensitivity to dexamethasone in three study groups established on the basis of the tumor site-to-diencephalic structures distance. A relatively higher frequency of disturbances in dexamethasone inhibition in patients with brain tumors suggests grave disorders induced in glucocorticoid secretion regulation by chronic stress.


Versatile clinical information system design for emergency departments.
Compared to other hospital units, the emergency department presents some distinguishing characteristics of its own. Emergency health-care delivery is a collaborative process involving the contribution of several individuals who accomplish their tasks while working autonomously under pressure and sometimes with limited resources. Effective computerization of the emergency department information system presents a real challenge due to the complexity of the scenario. Current computerized support suffers from several problems, including inadequate data models, clumsy user interfaces, and poor integration with other clinical information systems. To tackle such complexity, we propose an approach combining three points of view, namely the transactions (in and out of the department), the (mono and multi) user interfaces and data management. Unlike current systems, we pay particular attention to the user-friendliness and versatility of our system. This means that intuitive user interfaces have been conceived and specific software modeling methodologies have been applied to provide our system with the flexibility and adaptability necessary for the individual and group coordinated tasks. Our approach has been implemented by prototyping a web-based, multiplatform, multiuser, and versatile clinical information system built upon multitier software architecture, using the Java programming language.


Burn and cut injuries related to job stress among kitchen workers in Japan.
To clarify the correlation between kitchen work-related burns and cuts and job stress, a self-administered questionnaire survey was conducted involving 991 kitchen workers among 126 kitchen facilities. The demographics, condition of burns and cuts, job stress with the Brief Job Stress Questionnaire (BJSQ), health condition, and work-related and environmental factors were surveyed. Multiple logistic regression models and trend tests were used according to quartiles (Q1, Q2, Q3, and Q4) of each sub-scale BJSQ. After adjustment for potential confounding variables, burns/cuts were associated with a higher score category (Q4) of job demands (OR: 2.56, 95% CI: 1.10-6.02/OR: 2.72, 95% CI: 1.30-5.69), psychological stress (OR: 4.49, 95% CI: 2.05-9.81/OR: 3.52, 95% CI: 1.84-6.72), and physical stress (OR: 2.41, 95% CI: 1.20-4.98/OR 2.16, 95% CI: 1.16-4.01). The ORs of the burn/cut injures increased from Q1 to Q4 with job demands (p for trend = 0.045/0.003), psychological stress (p for trend<0.001/0.001), and physical stress (p for trend = 0.006/0.005), respectively. These findings suggest that kitchen work-related burns and cuts are more likely to be correlated with job stress, and the higher the job stress score, the higher the frequency of burns and cuts among kitchen workers.


Reflections on the decade of the neglected tropical diseases.
Neglected tropical diseases (NTDs) are a group of diseases that disproportionately affect the poorest of the poor. While for years attention has focused on single diseases within this group, efforts during the past decade have resulted in their being grouped together to highlight that they are fundamentally diseases of neglected populations. The formation of a World Health Organization department to address these diseases consolidated the efforts of the many stakeholders involved. In the past decade, focus has shifted from the Millennium Development Goals (MDGs), where NTDs are not mentioned, to the Sustainable Development Goals (SDGs), where NTDs are not only mentioned, but clear indicators are provided to measure progress. It has also been a decade where many NTD programmes have scaled up rapidly thanks to work by affected countries through their master plans, the commitment of partners and the unprecedented donations of pharmaceutical manufacturers. This decade has also seen the scaling down of programmes and acknowledgement of the elimination of some diseases in several countries. Given the successes to date, the challenges identified over the past decade and the opportunities of the coming decade, the NTD Programme at the WHO is working with partners and stakeholders to prepare the new NTD roadmap for 2021 to 2030. The focus is on three major paradigm shifts: a change of orientation from process to impact, a change in technical focus from diseases to delivery platforms and a change from an external-based agenda and funding to a more country-led and funded implementation within health systems. This article reviews the past decade and offers a glimpse of what the future might hold for NTDs as a litmus test of SDG achievements.


Employee satisfaction: an integral component of total quality.
As part of the Total Quality Management process, the leadership of Rush Medical Laboratories, with a staff of 400, made an initial commitment to focus on their own employees as the most important customers. Only after the employees' development, their help, their support, and their empowerment could Rush Medical Laboratories make the improvements in customer relationships and obtain the operations improvement, cost savings, and productivity necessary to maintain a competitive edge. This article outlines the numerous employee initiatives that have resulted from this commitment. All of these initiatives were successful at some point during the 5 or more years since the incorporation of TQM within Rush Medical Laboratories. In the spirit of continuous improvement, some have been modified or discontinued and replaced by others. This article provides an overview of the many improvements that are possible when employees are provided a forum in which to voice their needs, and it challenges the management and employees of all laboratories to focus on this vital component of total quality.


A novel antioxidant agent caffeic acid phenethyl ester prevents long-term mobile phone exposure-induced renal impairment in rat. Prognostic value of malondialdehyde, N-acetyl-beta-D-glucosaminidase and nitric oxide determination.
Caffeic acid phenethyl ester (CAPE), a flavonoid like compound, is one of the major components of honeybee propolis. It has been used in folk medicine for many years in Middle East countries. It was found to be a potent free radical scavenger and antioxidant recently. The aim of this study was to examine long-term applied 900 MHz emitting mobile phone-induced oxidative stress that promotes production of reactive oxygen species (ROS) and, was to investigate the role of CAPE on kidney tissue against the possible electromagnetic radiation (EMR)-induced renal impairment in rats. In particular, the ROS such as superoxide and nitric oxide (NO) may contribute to the pathophysiology of EMR-induced renal impairment. Malondialdehyde (MDA, an index of lipid peroxidation) levels, urinary N-acetyl-beta-D-glucosaminidase (NAG, a marker of renal tubular injury) and nitric oxide (NO, an oxidant product) levels were used as markers of oxidative stress-induced renal impairment and the success of CAPE treatment. The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in renal tissue were determined to evaluate the changes of antioxidant status. The rats used in the study were randomly grouped (10 each) as follows: i) Control group (without stress and EMR), ii) Sham-operated rats stayed without exposure to EMR (exposure device off), iii) Rats exposed to 900 MHz EMR (EMR group), and iv) A 900 MHz EMR exposed + CAPE treated group (EMR + CAPE group). In the EMR exposed group, while tissue MDA, NO levels and urinary NAG levels increased (p < 0.0001), the activities of SOD, CAT, and GSH-Px in renal tissue were reduced (p < 0.001). CAPE treatment reversed these effects as well (p < 0.0001, p < 0.001 respectively). In conclusion, the increase in NO and MDA levels of renal tissue, and in urinary NAG with the decrease in renal SOD, CAT, GSH-Px activities demonstrate the role of oxidative mechanisms in 900 MHz mobile phone-induced renal tissue damage, and CAPE, via its free radical scavenging and antioxidant properties, ameliorates oxidative renal damage. These results strongly suggest that CAPE exhibits a protective effect on mobile phone-induced and free radical mediated oxidative renal impairment in rats.


Direct Dynamic Protein-Affinity Selection Mass-Spectrometry.
A new methodology is described enabling the affinity screening of potential ligands towards the human estrogen receptor alpha ligand binding domain (ERalpha-LBD). In-solution incubation is performed of the analyte and the His-tagged ERalpha-LBD. The bound complex is immobilized on a nickel-loaded protein-affinity selection column, where after the unbound fraction is removed. The immobilized protein-ligand complex is exposed to a decreased pH value and an increased organic modifier concentration releasing the ligand for MS detection, and precipitating the proteins on a filter positioned between the affinity column and the mass spectrometer. The trapping column can be regenerated for reuse at least 70 times. The advantages of the methodology over existing methodologies are the absence of a pre-concentration as well as a chromatographic separation step, resulting in a significantly shorter analysis time compared to previously described procedures, and in addition, allowing the determination of solutes with unfavorable chromatographic properties. The overall analysis time now can be reduced about 250% to approximately 6 min. Replacing the filters after every measurement results in an intra-day standard deviation of 14.8% and an inter-day standard deviation of 21.3%.


Enhanced thecal androgen production is prenatally programmed in an ovine model of polycystic ovary syndrome.
One of the hallmarks of polycystic ovary syndrome (PCOS) is increased ovarian androgen secretion that contributes to the ovarian, hormonal, and metabolic features of this condition. Thecal cells from women with PCOS have an enhanced capacity for androgen synthesis. To investigate whether this propensity is a potential cause, rather than a consequence, of PCOS, we used an ovine prenatal androgenization model of PCOS and assessed ewes at 11 months of age. Pregnant Scottish Greyface ewes were administered 100 mg testosterone propionate (TP) or vehicle control twice weekly from d 62 to 102 of gestation, and female offspring (TP = 9, control = 5) were studied. Prenatal TP exposure did not alter ovarian morphology or cyclicity, or plasma androgen, estrogen, and gonadotropin concentrations, at this stage. However, follicle function was reprogrammed in vivo with increased proportions of estrogenic follicles (P < 0.05) in the TP-exposed cohort. Furthermore, in vitro the thecal cells of follicles (>4 mm) secreted more LH-stimulated androstenedione after prenatal androgenization (P < 0.05), associated with increased basal expression of thecal StAR (P < 0.01), CYP11A (P < 0.05), HSD3B1 (P < 0.01), CYP17 (P < 0.05), and LHR (P < 0.05). This provides the first evidence of increased thecal androgenic capacity in the absence of a PCOS phenotype, suggesting a thecal defect induced during fetal life.


Epidemiology and pathogenesis of heart failure with preserved ejection fraction.
Heart failure (HF) is a complex syndrome that affects approximately 6.5 million adults in the United States. About half of the 6.5 million adults with HF are estimated to be individuals with heart failure with preserved ejection fraction (HFpEF). It is a common cause for poor quality of life, increased health-care resource utilization, and early mortality. HF incidence has risen to epidemic proportions in the recent years. This review attempts to address the epidemiology and pathophysiology of HFpEF. The incidence of HFpEF increased from 48% to 57% from 2000 to 2007 with a slight decrease in 2010 to 52%. The temporal trends in heart failure show an overall stable incidence of HF over the last two decades with increasing incidence of HFpEF and decreasing HFrEF incidence. Many etiologies contribute to the development of HFpEF which makes the treatment very challenging. Pathophysiology of HFpEF is multifaceted stemming from several disease-specific aspects of inflammation and endothelial function, cardiomyocyte hypertrophy and fibrosis, ventricular-vascular uncoupling, pulmonary hypertension and chronotropic incompetence. Hence identifying the risk factors and etiologies is imperative to achieve optimal outcomes in this population. Newer insights into myocardial remodeling have led to an interesting finding of abnormal fibroblasts in HFpEF which are apoptosis resistant and initiate the development of an abnormal myocardial matrix resulting in initiation and progression of the disease. Upregulation of ROS has also been implicated in HFpEF. Further investigation could provide new avenues to target therapeutics specifically to stop initiation and progression of fibrosis.


Comprehensive Proteomic Study of the Antiproliferative Activity of a Polyphenol-Enriched Rosemary Extract on Colon Cancer Cells Using Nanoliquid Chromatography-Orbitrap MS/MS.
In this work, a proteomics strategy based on nanoliquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) using an Orbitrap high-resolution mass spectrometer together with stable isotope dimethyl labeling (DML) is applied to quantitatively examine relative changes in the protein fraction of HT-29 human colon cancer cells treated with different concentrations of a polyphenol-enriched rosemary extract over the time. The major objective of this study was to gain insights into the antiproliferative mechanisms induced by rosemary polyphenols. Using this methodology, 1909 and 698 proteins were identified and quantified in cell extracts. The polyphenol-enriched rosemary extract treatment changed the expression of several proteins in a time- and concentration-dependent manner. Most of the altered proteins are implicated in the activation of Nrf2 transcription factor and the unfolded protein response. In conclusion, rosemary polyphenols induced proteomic changes that were related to the attenuation of aggresome formation and activation of autophagy to alleviate cellular stress.


Peritraumatic and persistent dissociation as predictors of PTSD symptoms in a female cohort.
Recent research has investigated peritraumatic and persistent dissociation as a possible predictive factor for posttraumatic stress disorder (PTSD). The current study aimed to add to this literature by examining dissociative responses in female assault survivors (N = 92 at initial assessment; n = 62 at follow-up). Dissociative symptoms experienced at 3 time points were assessed: peritraumatic dissociation (PD), persistent dissociation-initial (M = 28.2 days posttrauma) and follow-up (M = 224.9 days posttrauma), as well as initial and follow-up PTSD symptoms. We hypothesized that PD and persistent dissociative symptoms would predict chronic PTSD symptoms at the follow-up assessment with initial PTSD symptoms and assault type in the model. Hierarchical regression resulted in a significant model predicting 39% of the variance in follow-up PTSD symptom scores (p < .001). Both peritraumatic and follow-up persistent dissociative symptoms significantly and uniquely added to the variance explained in follow-up PTSD symptom score contributing 4% (p = .05) and 8% (p = .008) of the variance, respectively. Results support the predictive value of peritraumatic and persistent dissociative symptoms, and the findings suggest that persistent dissociation may contribute to the development and continuation of PTSD symptoms. We discuss the implications for assessment and possible treatment of PTSD as well as future directions.


STUDIES ON AN EPITHELIAL (GLAND) CELL JUNCTION. II. SURFACE STRUCTURE.
The surface structure of a gland epithelium (Drosophila salivary gland), particularly that at the junction between cells, was examined under the electron microscope. The junctional surface, which in the preceding paper was shown to be highly permeable to ions, has the following structural characteristics. About two-thirds of it are profusely infolded; the surface membranes of adjoining cells interdigitate and present desmosomes. The width of the intercellular space varies considerably. The remainder of the junctional surface, the third that abuts on the lumen, is rather straight. Here, the cell membranes are aligned parallel at a distance of 150 A, and interconnected at regular intervals of 100 A. The connecting material has a high electron opacity, and is about as thick as the cell membranes, but, unlike the latter, has no resolvable unit membrane structure. The surface at the cell base, which in the preceding paper was shown to be rather impermeable, is infolded and resembles the infolded junctional region. The luminal surface exhibits microvilli. Critical surface dimensions are given, and the implications of surface structure in intercellular permeability are discussed.


Genetic linkage studies of thyroid peroxidase (TPO) gene in families with TPO deficiency.
We have conducted biochemical and genetic studies in five unrelated families (denoted A, C, R, P, and G), which included nine goitrous subjects (five borderline euthyroid and four hypothyroid) with complete (n = 6) or partial (n = 3) thyroid peroxidase (TPO) deficiency. Thyroid tissue was obtained from four subjects, respectively, in families A, C, and R. No iodide organification or iodide incorporation into protein was present in families A and C. The two affected siblings in family R had a low normal tissue thyroperoxidase activity. Using a 0.8-kilobase (kb) cDNA clone (pM5) encoding 30% of the cDNA of human TPO gene down-stream from basepair 730 and four restriction enzymes (TaqI, PstI, BglI, and BglII), we were unable to find any polymorphisms in family A. In another family (C) blood samples were obtained from only two family members, and consequently, it was not possible to determine linkage. DNA from families G, P, and C showed biallelic polymorphisms when digested with BglII, at 8.7 and 8.5 kb. In family R we detected two biallelic polymorphisms at 9.0 and 8.5 kb, and the 9.0-kb bands were clearly larger than 8.7-kb bands found in the other subjects. Also, there was an absence of a 4.0- to 3.9-kb band that may represent a partial gene deletion. With PstI-restricted DNA a possible deletion of 5.5-kb band was also present in affected siblings of family R. The logarithm of odds (Lod) score analyzed from the family with inbreeding (R) was compatible with linkage of disease and the TPO gene (Lod = 2.08). When this method was used with families G and P, the Lod score was inconsistent with linkage between disease and the TPO gene. These data suggest that the cause of TPO deficiency in these families is heterogeneous. However, the restriction fragment length polymorphism pattern of BglII-restricted DNA in the R family strongly suggests that a partial TPO gene deletion has occurred in this family.


Radiometric detection of yeasts in blood cultures of cancer patients.
During a 12-month period, 19,457 blood cultures were collected. Yeasts were isolated from 193 cultures derived from 76 cancer patients. Candida albicans or Candida tropicalis accounted for 79% of isolates. Of the three methods compared, the radiometric method required 2.9 days to become positive, "blind" subculture required 2.6 days, and Gram stains required 1 day. However, the radiometric method was clearly superior in detecting positive cultures, since 73% of all cultures were first detected radiometrically, 22% were detected by subculture, and only 5% were detected by Gram stain. Although 93% of the isolates were detected by aerobic culture, five (7%) isolates were obtained only from anaerobic cultures. Seven days of incubation appear to be sufficient for the radiometric detection of yeasts.


Improved healing of transected rabbit Achilles tendon after a single injection of cartilage-derived morphogenetic protein-2.
Achilles tendon ruptures in humans might be treated more efficiently with the help of a growth factor. Cartilage-derived morphogenetic protein-2 has been shown to induce formation of tendon-like tissue. Cartilage-derived morphogenetic protein-2 has a positive effect on mechanical parameters for tendon healing in a rabbit model with Achilles tendon transection. Controlled laboratory study. The right Achilles tendon of 40 rabbits was transected without tendon suture. Cartilage-derived morphogenetic protein-2 (10 micro g) or vehicle control (acetate buffer) was injected locally 2 hours postoperatively. All tendons were tested biomechanically at 8 and 14 days, and treated tendons were histologically and radiographically evaluated at 56 days. At 14 days, both failure load and stiffness of treated tendons were increased by 35%. The treated tendons had significantly larger callus size at 8 and 14 days. Histologic and radiographic examination showed no signs of ossification in the treated tendons after 56 days. A single injection of cartilage-derived morphogenetic protein-2 led to a stronger and stiffer tendon callus than that in the controls without inducing bone formation. Similar results from a larger animal model would suggest a possible future use of cartilage-derived morphogenetic protein-2 in the treatment of human Achilles tendon ruptures.


Detecting, reporting, and analysis of priority diseases for routine public health surveillance in Liberia.
Public health officials depend on timely, complete, and accurate surveillance data for decision making. The quality of data generated from surveillance is highly dependent on external and internal factors which may either impede or enhance surveillance activities. One way of identifying challenges affecting the quality of data generated is to conduct a data quality audit. This case study, based on an audit conducted by residents of the Liberia Frontline Field Epidemiology Training Program, was designed to be a classroom simulation of a data quality audit in a health facility. It is suited to enforce theoretical lectures in surveillance data quality and auditing. The target group is public health trainees, who should be able to complete this exercise in approximately 2 hours and 30 minutes.


Reactivation of chlamydial genital tract infection in mice.
A model was developed to study chlamydial quiescence in C3H/HeN (C3H) and C57BL/6N (C57) mice following genital tract infection by Chlamydia trachomatis MoPn. Reactivation of chlamydial shedding following immunosuppression indicated that viable MoPn remained in the genital tract for up to 4 or 5 weeks after the apparent clearance of a primary infection. Either cyclophosphamide or cortisone acetate treatment could cause reactivation, but cyclophosphamide was more effective. However, the frequency of reactivation by either drug diminished with time in both mouse strains. Progesterone treatment prior to infection of C57 mice greatly reduced the frequency of reactivation by cyclophosphamide and also correlated with the development of marked fluid accumulation and distension of the uterine horns in the vast majority of those animals. This pathology was apparent by 5 to 7 weeks postinfection and was consistently seen through 110 days postinfection. Neither of these phenomena was observed in C57 mice that had not been treated with progesterone or in C3H mice under any conditions tested. The infecting dose of MoPn did not clearly influence the frequency of reactivation in either inbred strain as defined by this model.


Peripheral parenteral nutrition in protracted hyperemesis gravidarum--report of two cases and a literature review.
Hyperemesis gravidarum is defined as severe nausea and vomiting during the first trimester of pregnancy. It is characterized by dehydration, electrolyte imbalance, ketonuria and weight loss of more than 5% of body weight and it usually requires hospitalization. Traditionally, total parenteral nutrition has been used when patients with hyperemesis gravidarum fail to respond to conservative measures, including dietary manipulation and antiemetics. Total parenteral nutrition has been shown to be an effective method of nutritional support during pregnancy but it is expensive and has potentially serious complications. Peripheral parenteral nutrition reduces the risk of complications, but caloric intake is limited. A small number of investigators have suggested using enteral nutrition as an alternative to total parenteral nutrition. Herein we report two cases of hyperemesis gravidarum successfully treated with an effective regimen of peripheral parenteral nutrition.


Investigating the origins of political views: biases in explanation predict conservative attitudes in children and adults.
We tested the hypothesis that political attitudes are influenced by an information-processing factor - namely, a bias in the content of everyday explanations. Because many societal phenomena are enormously complex, people's understanding of them often relies on heuristic shortcuts. For instance, when generating explanations for such phenomena (e.g., why does this group have low status?), people often rely on facts that they can retrieve easily from memory - facts that are skewed toward inherent or intrinsic features (e.g., this group is unintelligent). We hypothesized that this bias in the content of heuristic explanations leads to a tendency to (1) view socioeconomic stratification as acceptable and (2) prefer current societal arrangements to alternative ones, two hallmarks of conservative ideology. Moreover, since the inherence bias in explanation is present across development, we expected it to shape children's proto-political judgments as well. Three studies with adults and 4- to 8-year-old children (N = 784) provided support for these predictions: Not only did individual differences in reliance on inherent explanations uniquely predict endorsement of conservative views (particularly the stratification-supporting component; Study 1), but manipulations of this explanatory bias also had downstream consequences for political attitudes in both children and adults (Studies 2 and 3). This work contributes to our understanding of the origins of political attitudes.


Effects of biochar and nitrogen addition on nutrient and Cd uptake of Cichorium intybus grown in acidic soil.
Biochar is an organic amendment used for soil remediation, there are only a few studies documenting the effects of nitrogen on the role of biochar in contaminated soils. A pot experiment was conducted to investigate the impacts of biochar (0%, 1%, and 2.5%, w/w) and nitrogen (0, 100, and 200 mg N kg-1) on plant growth, nutrient and cadmium (Cd) uptake of Cichorium intybus. N, P, Ca, Mg, and Cd concentrations increased with N level in 0% and 1% biochar treatments. In plants treated with 2.5% biochar, 200 mg N kg-1 addition caused significant reductions of N, P, Ca, Mg, and Cd concentrations in comparison to 100 mg N kg-1 treatments. Nitrogen promoted shoot biomass at all biochar treatments, while biochar had no effect on shoot biomass in 0 and 200 mg N kg-1 addition treatments. Nitrogen also significantly increased N, P, K, Ca, Mg, and Cd contents in the 0% and 1.5% biochar addition treatments. Although soil DTPA-extractable Cd concentration showed the lowest values in 1% biochar in combination with 100 and 200 mg N kg-1 addition treatments, lowest shoot Cd concentration, and relatively high shoot biomass occurred in the 2.5% biochar + 200 mg N kg-1 treatment. Based on these results, biochar application at its highest rate (2.5%) in combination with high N supply (200 mg N kg-1) contributed to both crop yield and agricultural product safety. N input alone might increase the risk of human health, and the optimum N dose should be determined during phytostabilization process.


Liver.
The liver's unique metabolism and relationship to the gastrointestinal tract make it an important target of the toxicity of drugs and xenobiotics. The developmental changes that occur in the liver's metabolic activity from birth to adolescence contribute to the varied sensitivity to toxins seen in the pediatric population. Hepatic drug metabolism, often with an imbalance between the generation of toxic metabolites and detoxification processes, can influence the degree of hepatotoxicity. The decreased capacity of the neonatal liver to metabolize, detoxify, and excrete xenobiotics explains the prolonged action of drugs such as phenobarbital, theophyline, and phenytoin. The reduced capacity of glucuronide conjugation in the neonate not only predisposes them to physiologic jaundice but also is probably responsible for the chloramphenicol-induced gray infant syndrome. Age-related sensitivity to drugs is attributable in part to differences in metabolic activity. For example, young children are more resistant to acetaminophen hepatotoxicity when compared with adults, whereas children are more susceptible to valproic acid-induced toxicity. The resistance to acetaminophen toxicity is attributable to biochemical differences in young children. In children, sulfation predominates over glucuronidation, leading to decreased formation of toxic intermediates. In addition, infants have a greater capacity to synthesize glutathione, thereby inactivating toxic metabolites of acetaminophen more effectively. Hepatic toxicity as a result of drugs and environmental toxins presents a wide spectrum of clinical disease. Hepatitis is the most common presentation, but every major type of liver pathology can occur. Most drug reactions are attributable to idiosyncratic hepatotoxins; therefore, liver injury occurs rarely. The diagnosis of toxin-induced liver disease requires a high index of suspicion and often entails the exclusion of other causes of liver disease in children. Drug or environmental xenobiotic-induced hepatotoxicity should be considered in the setting of identified exposure or when other causes of childhood liver disease are excluded. Children who take medications that are known to be hepatotoxic, such as anticonvulsants and antineoplastic drugs, need frequent monitoring for evidence of hepatic toxicity. The treatment is often nonspecific; the most important intervention is the prompt discontinuation of the drug or removal of the environmental toxin. A specific antidote is available only for acetaminophen intoxication. In cases of severe toxicity, the patient may develop liver failure. Liver transplantation may be necessary for patients whose liver failure does not resolve.


Regulation of Interferon-γ receptor (IFN-γR) expression in macrophages during Mycobacterium tuberculosis infection.
Interferon-gamma (IFN-γ) is a key cytokine that mediates immunity to tuberculosis (TB). Mycobacterium tuberculosis (M. tb) is known to downregulate the surface expression of IFN-γ receptor (IFN-γR) on macrophages and peripheral blood mononuclear cells (PBMCs) of patients with active TB disease. Many M. tb antigens also downmodulate IFN-γR levels in macrophages when compared with healthy controls. In the current study, we aimed at deciphering key factors involved in M. tb mediated downregulation of IFN-γR levels on macrophage surface. Our data showed that both M. tb H37Rv and M. bovis BCG infections mediate downmodulation of IFN-γR on human macrophages. This downmodulation is regulated at the level of TLR signaling pathway, second messengers such as calcium and cellular kinases i.e. PKC and ERK-MAPK, indicating that fine tuning of calcium response is critical to maintaining IFN-γR levels on macrophage surface. In addition, genes in the calcium and cysteine protease pathways which were previously identified by us to play a negative role during M. tb infection, also regulated IFN-γR expression. Thus, modulations in IFN-γR levels by utilizing host machinery may be a key immune suppressive strategy adopted by the TB pathogen to ensure its persistence and thwart host defense.


Cost-effectiveness of combination versus sequential docetaxel and carboplatin for the treatment of platinum-sensitive, recurrent ovarian cancer.
In a randomized controlled trial (RCT) of patients with recurrent, platinum-sensitive ovarian cancer, the combination weekly docetaxel and carboplatin was associated a with progression-free survival (PFS) of 13.7 months compared with 8.4 months for sequential, single-agent docetaxel followed by carboplatin. The objective of the current study was to construct a cost-utility model to compare these 2 regimens with the incorporation of prospectively collected quality-of-life (QoL) data. An RCT of concurrent docetaxel and carboplatin (cDC) versus docetaxel followed by carboplatin (sequential docetaxel and carboplatin [sDC]) was the basis for a Markov decision model, and the primary effectiveness outcome was PFS. Costs were estimated using US dollars based on Medicare reimbursements for chemotherapy regimens, bone marrow support, and management of adverse events. QoL data obtained using the Functional Assessment of Cancer Therapy-General questionnaire were converted to utilities. Costs and incremental cost-effectiveness ratios (ICERs) were reported in US dollars per quality-adjusted life year (QALY). Extensive 1-way sensitivity analyses and a Monte Carlo probabilistic sensitivity analysis were performed. The least expensive strategy was sDC, which cost an average of $20,381, compared with cDC, which cost an average of $25,122. cDC had an ICER of $25,239 per QALY compared with sDC. cDC remained cost-effective, with an ICER <$50,000 per QALY, over a range of costs and estimates. In Monte Carlo sensitivity analysis using a $50,000 per QALY willingness-to-pay threshold, cDC was either dominant or cost-effective with an ICER <$50,000 per QALY in 83% of simulations. Combined weekly cDC appeared to be cost-effective compared with sDC as treatment strategy for patients with platinum-sensitive ovarian cancer, even when accounting for slightly lower QoL during treatment.


Diagnostic utility of procalcitonin for bacterial infections in diabetic ketoacidosis.
Procalcitonin is a widely used infection biomarker; however, its utility in identifying bacterial infection in diabetic ketoacidosis (DKA) is unclear. We aimed to evaluate its diagnostic performance for detecting DKA cases triggered by bacterial infections. We reviewed 303 case records of patients aged ≥ 13 years with DKA admitted to the emergency department, PGIMER (Chandigarh), between 2017 and 2022. Baseline procalcitonin was measured by electrochemiluminescence immunoassay, and a value > 0.5 ng/mL was considered elevated. Both microbiological reference standard (MRS) and composite reference standard (CRS) were used to evaluate the diagnostic performance of procalcitonin. 151/303 (49.8%) DKA cases had infection precipitations. Bacterial infections were present in 98 patients (53 microbiologically confirmed), of which urinary tract infection (n = 42), pneumonia (n = 19), skin and soft-tissue infection (n = 13), and bacteremia (n = 11) were common. The median value of procalcitonin was higher with bacterial infections than in patients without (3.68 vs. 1.00, P-value < 0.001). An elevated procalcitonin to detect bacterial infections in DKA had sensitivity 84.69%, specificity 34.15%, positive likelihood ratio (LR +) 1.29, and negative likelihood ratio (LR -) 2.44, against CRS. Against MRS, both LR + and LR - further decreased to 1.23 and 1.81, respectively. Using the receiver-operating-characteristic curve, an optimal cut-off of procalcitonin was calculated at 1.775 ng/ml against both CRS (area under curve 0.655, sensitivity 68.37%, specificity 59.02%, LR + 1.67, LR - 1.86, Yoden's index 0.274) and MRS (area under curve 0.616, sensitivity 67.92%, specificity 59.02%, LR + 1.66, LR - 1.84, Yoden's index 0.269). Procalcitonin does not help detect bacterial infections in patients with DKA at admission.


A syndemic of psychosocial health problems is associated with increased HIV sexual risk among Nigerian gay, bisexual, and other men who have sex with men (GBMSM).
Nigerian gay, bisexual and other men who have sex with men (GBMSM) experience negative psychosocial health problems, which may increase their risk for HIV infection. Few studies have explored the syndemic effect of co-occurring psychosocial health problems on HIV sexual risk among Nigerian GBMSM. We investigated the co-occurrence of syndemic psychosocial health problems and their synergistic effect on HIV risk behaviors. We assessed depressive symptoms, post-traumatic stress disorder, alcohol dependence, tobacco use, and hard-drug use. The outcome variables were the number of male sexual partners and consistent condom use. In a multivariable model, experiencing 4 or more psychosocial health problems - compared to experience none or one psychosocial health problem - was significantly associated with increasing number of male sexual partners. We found no statistically significant association between the number of syndemic psychosocial health problems and consistent condom use. Our study findings provides evidence of a synergistic relationship between negative psychosocial health factors and HIV sexual risk behavior. These findings underscore the importance of developing HIV prevention programming aimed at reducing HIV transmission risk that incorporate substance use and mental health treatments, in order to improve the overall health and quality of life for Nigerian GBMSM.


Are unsaturated isocyanides so different from the corresponding nitriles?
Simple unsaturated and cyclopropylic isocyanides are synthesized by an efficient and simple approach. These compounds with gradually increasing distance between the unsaturated moiety and the isonitrile group are studied by UV photoelectron spectroscopy and quantum chemical calculations, and also compared to the corresponding nitriles. The first photoelectron band of the unsaturated compounds is linked to removal of an electron from the HOMO, which corresponds to CC multiple-bond ionization in antibonding interaction with the π-isocyanide bond (in the same plane) for conjugated systems, or in antibonding interaction with the pseudo-π-CH(2) group for isolated systems. For the 1-ethenyl derivatives, both cyano and isocyano groups act as a π-electron acceptor from the vinyl group, but the isocyano π system is much more strongly destabilized (ionization energies (IEs) shift to smaller values) by vinyl (3.12 eV) than the cyano π system is (2.70 eV). In comparison with the 1-ethynyl derivatives, a less pronounced destabilization (2.69 eV) of π(NC) by the ethynyl system (1.86 eV for π(CN)), and nearly the same order of magnitude of the energetic gap between the total antibonding (π(CC)-π(NC)) and the total bonding (π(CC)+π(NC)) IEs for ethenyl and ethynyl compounds are noted. The huge values of these last-named data for H(2)C=CH-NC (3.85 eV) and for HC≡C-NC (4.04 eV) reflect the strong interaction between the unsaturated carbon-carbon moiety and the isocyanide group, and thus more efficient conjugation than for the corresponding nitriles.


Methods to study PAMP-triggered immunity using tomato and Nicotiana benthamiana.
Understanding the molecular basis of plant responses to pathogen-associated molecular patterns (PAMPs) is an active area of research in the field of plant-microbe interactions. A growing number of plant genes involved in various steps of PAMP-triggered immunity (PTI) pathways and microbial factors involved in the elicitation or suppression of PTI have been identified. These studies have largely relied on Arabidopsis thaliana and, therefore, most of the PTI assays have been developed and optimized for that model plant system. Although PTI is a conserved feature among plants, the response spectra vary across different species. Thus, there is a need for robust PTI assays in other pathosystems, such as those involving Solanaceae plant-pathogen interactions, which include many economically important plants and their diseases. We have optimized molecular, cellular, and whole-plant methods to measure PTI responses in two widely studied solanaceous species, tomato (Solanum lycopersicum) and Nicotiana benthamiana. Here, we provide detailed protocols for measuring various PTI-associated phenotypes, including bacterial populations after pretreatment of leaves with PAMPs, induction of reporter genes, callose deposition, activation of mitogen-activated protein kinases, and a luciferase-based reporter system. These methods will facilitate limited genetic screens and detailed characterization of potential PTI-related genes in model and economically important Solanaceae spp.-pathogen interactions.


Australian children with cerebral visual impairment: using what we know now to improve future approaches.
Little has been reported on Australian children with Cerebral Vision Impairment (CVI). This paper aims to present the outcome of an audit focussed on children with the primary diagnosis of CVI, using findings from the Australian Childhood Vision Impairment Register (ACVIR). Records on 132 children (49% girls, 51% boys) from ACVIR data gathered from both the child's parent/guardian and their eye health professional were reviewed. The child's demographics, level of vision impairment, birth history, diagnostic journey, secondary ocular diagnoses, comorbidities and low vision support were analyzed. Several correlations were investigated using a Kendall's tau-b analysis including the relationship between vision and age of diagnosis; level of vision and developmental delay; and age of suspicion of visual impairment and age of diagnosis. The most common level of visual impairment was blindness (39%), and most children were suspected and diagnosed of visual impairment in the first 6 months of life. The majority of children were born full term (72%), weighing >2000gms (84%). Nearly half of the cohort of children (48%) had a secondary ocular diagnosis with 44% having nystagmus. The majority of children (80%) had additional health problems, and 85% of children had additional disabilities, with 79% having developmental delay. While the findings of this audit cannot be generalized to a wider population of Australian children with CVI, the outcome encourages continued discussion on CVI, to explore comprehensive assessment approaches which facilitate timely and accurate diagnosis.


Imaging Performance of a Dynamic Positron Emission Tomograph: Positome IIIp.
This paper documents modifications to an older PET system to improve its dead time, scatter fraction, and spatial resolution in high count rate, short duration studies. A new dual-tapered collimator reduces scatter by 33 percent while providing excellent resolution uniformity in all slices. A data encoding scheme produces uniformly sampled parallel projections from the coincidence data in real time while the detector array executes an orbital motion. The image uniformity, scatter compensation and high count-rate performance have been validated up to 40 kBq/cc in a 20 cm flood source. The errors in image quantification due to counting statistics, live time, and random counts are estimated from repeated measurements on a contrast phantom at high count-rates. The effects of two methods of scatter compensation on image contrast are shown in contrast phantoms and a typical glucose utilization study. Blood flow measurements using 0-15 labeled water bolus method, made under different physiological conditions, reflected the changes expected. The true count efficiency of 75 kcps/(uCi/cc) permits these studies to be done with only 500-900 MBq (13-25 mCi) injected activity.


Delivery of ERAS Care in an Academic Hospital: An Analysis of Pathway Deviations and Obstacles to Adherence.
Enhanced Recovery after Surgery (ERAS) pathways in colorectal surgery improve outcomes and reduce disparities, but pathway adherence rates are variable. Sustainability of adherence following initial implementation, particularly in academic settings with trainee involvement, is underexplored. This study measures and describes ERAS adherence for 163 consecutive patients undergoing elective colorectal resection in an academic colorectal surgery department with a well-established ERAS pathway. Providers, including residents and nursing staff, were surveyed regarding pathway knowledge and obstacles to adherence. Adherence was higher preoperatively (80%) and intraoperatively (93%) than postoperatively (61%). Opioid-sparing analgesia and bowel motility agents were underdosed on up to 63% of hospital days, without clinical rationale in ≥50% of cases. Providers cited peer teaching (71%) as the primary source of pathway knowledge and identified individual surgeon preferences as an obstacle to adherence. Formalized ERAS pathway education, communication, and coordination among attending physicians are needed to reduce provider-driven deviation in an academic setting.


Hesperidin Methyl Chalcone reduces extracellular Aβ(25-35) peptide aggregation and fibrillation and also protects Neuro 2a cells from Aβ(25-35) induced neuronal dysfunction.
In the present study, we evaluated the neuroprotective potential of Hesperidin Methyl Chalcone (HMC) against the neurotoxicity induced by Aβ(25-35) peptide. HMC demonstrated higher free-radical scavenging activity than Hesperidin in initial cell-free studies. Investigations using the fluorescent dye thioflavin T with Aβ(25-35) peptide showed that HMC has the ability to combat extracellular amyloid aggregation by possessing anti-aggregation property against oligomers and by disaggregating mature fibrils. Also, the results of the molecular simulation studies show that HMC ameliorated oligomer formation. Further, the anti-Alzheimer's property of HMC was investigated in in vitro cell conditions by pre-treating the neuro 2a (N2a) cells with HMC before inducing Aβ(25-35) toxicity. The findings demonstrate that HMC increased cell viability, reduced oxidative stress, prevented macromolecular damage, allayed mitochondrial dysfunction, and exhibited anticholinesterase activity. HMC also reduced Aβ induced neuronal cell death by modulating caspase-3 activity, Bax expression and Bcl2 overexpression, demonstrating that HMC pre-treatment reduced mitochondrial damage and intrinsic apoptosis induced by Aβ(25-35).In silico evaluation against potential AD targets reveal that HMC could be a potent inhibitor of BACE-1, inhibiting the formation of toxic Aβ peptides. Overall, the findings imply that the neuroprotective efficacy of HMC has high prospects for addressing a variety of pathogenic consequences caused by amyloid beta in AD situations and alleviating cognitive impairments.


Shiftwork and Light at Night Negatively Impact Molecular and Endocrine Timekeeping in the Female Reproductive Axis in Humans and Rodents.
Shiftwork, including work that takes place at night (nightshift) and/or rotates between day and nightshifts, plays an important role in our society, but is associated with decreased health, including reproductive dysfunction. One key factor in shiftwork, exposure to light at night, has been identified as a likely contributor to the underlying health risks associated with shiftwork. Light at night disrupts the behavioral and molecular circadian timekeeping system, which is important for coordinated timing of physiological processes, causing mistimed hormone release and impaired physiological functions. This review focuses on the impact of shiftwork on reproductive function and pregnancy in women and laboratory rodents and potential underlying molecular mechanisms. We summarize the negative impact of shiftwork on female fertility and compare these findings to studies in rodent models of light shifts. Light-shift rodent models recapitulate several aspects of reproductive dysfunction found in shift workers, and their comparison with human studies can enable a deeper understanding of physiological and hormonal responses to light shifts and the underlying molecular mechanisms that may lead to reproductive disruption in human shift workers. The contributions of human and rodent studies are essential to identify the origins of impaired fertility in women employed in shiftwork.


Antibacterial wound dressing from chitosan/polyethylene oxide nanofibers mats embedded with silver nanoparticles.
Novel antibacterial nanomaterials have been developed for biomedical applications. The present study involves the preparation and properties of antibacterial nanofibers from chitosan/polyethylene oxide electrospun nanofibers incorporated with silver nanoparticles. Silver nanoparticles were efficiently synthesized in situ after ultra violet (UV) with AgNO3 as precursor and chitosan/polyethylene oxide as reducing agent and protecting agent, respectively. Then the resultant solutions were electrospun into nanofibers. The formation of silver nanoparticles was confirmed with ultraviolet visible (UV-vis) and transmission electron microscopy (TEM), and the electrospun nanofibers were characterized by scanning electron microscopy and energy dispersive X-ray. The resultant fibers exhibited uniform morphology with silver nanoparticles distributed throughout the fiber. Also, the fibers showed certain tensile strength and excellent antibacterial activity against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. Sustained release of silver nanoparticles from fibers could last for over 72 h. The silver-containing chitosan/polyethylene oxide nanofibers showed excellent cytocompatibility.


Imaging diagnosis-malignant peripheral nerve sheath tumor presenting as an intra-axial brain mass in a young dog.
A 3-year-old Labrador retriever was presented with acute onset seizures. Magnetic resonance imaging demonstrated an intra-axial mass affecting the right temporal lobe of the brain. Surgical resection and histopathological findings were most consistent with a malignant peripheral nerve sheath tumor. After initial recovery, deterioration 3 months post surgery prompted euthanasia. Post-mortem revealed a mass protruding from the ventral surface of the temporal lobe, encroaching upon the optic chiasm and invading the brain. Histopathology findings were again consistent with malignant peripheral nerve sheath tumor. Although rare, this tumor should be included as a possible differential diagnosis for intra-axial brain masses in dogs.


Calorie restriction modulates hippocampal NMDA receptors in diet-induced obese rats.
Calorie restriction (CR) has attracted increased interest since CR enhances lifespan and alters age-related decline in hippocampal-dependent cognitive functions. Obesity is associated with poor neurocognitive outcome including impaired hippocampal synaptic plasticity and cognitive abilities such as learning and memory. N-Methyl-D-aspartate receptors (NMDARs) are linked to hippocampal-dependent learning and memory, which may be stabilized by CR. In the present study, we aimed to establish the effects of CR on NMDARs in CA1 region of hippocampus in obese and non-obese rats. In addition, malondialdehyde (MDA) levels were determined as a marker for lipid peroxidation (LPO) in hippocampus. Four groups were constituted as control group (C, n = 9), obese group (OB, n = 10), obese calorie-restricted group (OCR, n = 9), and non-obese calorie-restricted group (NCR, n = 10). OCR and NCR were fed with a 60% CR diet for 10 weeks. After 10 weeks of CR, the MDA levels significantly decreased in the calorie-restricted groups. Obesity caused significant decreases in NR2A and NR2B subunit expressions in the hippocampus. The hippocampal NR2A and NR2B levels significantly increased in the OCR group compared with the OB group (P < 0.05). In contrast, the hippocampal NR2A and NR2B levels significantly decreased in the NCR group compared with the C group (P < 0.05). Oxidative stress can be prevented by CR, and these data may provide a molecular and cellular mechanism by which CR may regulate NMDAR-mediated response against obesity-induced changes in the hippocampus.


Troughs developed in ice-stream shear margins precondition ice shelves for ocean-driven breakup.
Floating ice shelves of fast-flowing ice streams are prone to rift initiation and calving originating along zones of rapid shearing at their margins. Predicting future ice-shelf destabilization under a warming ocean scenario, with the resultant reduced buttressing, faster ice flow, and sea-level rise, therefore requires an understanding of the processes that thin and weaken these shear margins. Here, we use satellite data to show that high velocity gradients result in surface troughs along the margins of fast-flowing ice streams. These troughs are advected into ice-shelf margins, where the locally thinned ice floats upward to form basal troughs. Buoyant plumes of warm ocean water beneath ice shelves can be focused into these basal troughs, localizing melting and weakening the ice-shelf margins. This implies that major ice sheet drainages are preconditioned for rapid retreat in response to ocean warming.


A role for intrathymic B cells in the generation of natural regulatory T cells.
B cells inhabit the normal human thymus, suggesting a role in T cell selection. In this study, we report that B cells can modulate thymic production of CD4+ Foxp3+ T cells (regulatory T cells [Tregs]). Mice with transgenic expression of BAFF (BAFF-Tg) harbor increased numbers of Helios+ Foxp3+ thymic Tregs and, similar to some human autoimmune conditions, also exhibit increased numbers of B cells colonizing the thymus. Distinct intrathymic B cell subpopulations were identified, namely B220+, IgM+, CD23(hi), CD21(int) cells; B220+, IgM+, CD23(lo), CD21(lo) cells; and a population of B220+, IgM+, CD23(lo), CD21(hi) cells. Anatomically, CD19+ B cells accumulated in the thymic medulla region juxtaposed to Foxp3+ T cells. These intrathymic B cells engender Tregs. Indeed, thymic Treg development was diminished in both B cell-deficient BAFF-Tg chimeras, but also B cell-deficient wild-type chimeras. B cell Ag capture and presentation are critical in vivo events for Treg development. In the absence of B cell surface MHC class II expression, thymic expansion of BAFF-Tg Tregs was lost. Further to this, expansion of Tregs did not occur in BAFF-Tg/Ig hen egg lysozyme BCR chimeras, demonstrating a requirement for Ag specificity. Thus, we present a mechanism whereby intrathymic B cells, through the provision of cognate help, contribute to the shaping of the Treg repertoire.


Capnography-guided Endotracheal Intubation as an Alternative to Existing Intubation Methods in Rabbits.
Rabbits provide a unique challenge for routine endotracheal intubation in clinical practice because of various distinctive anatomic and physiologic features. Many previously proposed methods for endotracheal intubation in rabbits are limited by several factors, including the needs for expensive equipment and high levels of technical expertise. We evaluated capnography for its effectiveness in assisting endotracheal intubation in rabbits. New Zealand white rabbits were divided into 3 groups of 5 animals. In the first 2 groups, mainstream (nondiverting) or sidestream (diverting) capnography (MC and SC groups, re- spectively) was used; in the third group (LS group), a laryngoscope with a size 00 Miller blade was used to guide endotracheal tube placement. Anesthesia was induced through intramuscular administration of ketamine (10 mg/kg), medetomidine (0.1 mg/kg), and midazolam (1 mg/kg) mixed in the same syringe prior to administration. Intubation time was defined from the point of opening the jaws to the completion of the first capnogram after intubation. Intubation was accomplished successfully in all animals in both capnography groups, but 2 rabbits in the laryngoscopy group could not be intubated. Intubation time was compared among groups was compared by using one-way ANOVA, and posthoc Bonferroni testing was applied to isolate significant differences between groups. The intubation time (mean ± 1 SD) was 46.4 ± 12.6 s in the MC group, 147.2 ± 44.2 s in the SC group, and 385.0 ± 114.1 in the LS group, with intubation time significantly differing among all groups. In conclusion, both mainstream and sidestream capnography-guided endotracheal intubation techniques were more effective and efficient than conventional laryngoscope-guided endotracheal intubation in rabbits. Furthermore, mainstream capnography was preferred over sidestream capnography because mainstream capnography resulted in significantly shorter intubation times.


Ginsenoside Rb1 Blocks Ritonavir-Induced Oxidative Stress and eNOS Downregulation through Activation of Estrogen Receptor-Beta and Upregulation of SOD in Human Endothelial Cells.
We have previously shown that ritonavir (RTV), a highly active anti-retroviral therapy (HAART) drug, can cause endothelial dysfunction through oxidative stress. Several antioxidants including ginsenoside Rb1, a compound with antioxidant effect, can effectively block this side effect of RTV in endothelial cells. In the current study, we explored a mechanism by which ginsenoside Rb1 could protect these cells via binding of estrogen receptors (ERs). We found that several human endothelial cell lines differentially expressed ER-β and had very low levels of ER-α. RTV treatment significantly increased the production of reactive oxygen species (ROS) and decreased the expression of endothelial nitric oxidase synthase (eNOS) and superoxide dismutase (SOD) in HUVECs, while Rb1 effectively blocked these effects of RTV. These effects of Rb1 were effectively inhibited by silencing ER-β, indicating that ginsenoside Rb1 requires ER-β for its antioxidant activity in inhibiting the deleterious effect of RTV in human endothelial cells. Furthermore, Rb1 specifically activated ER-β transactivation activity by ER-β luciferase reporter assay. Rb1 competitively bound to ER-β, which was determined by the high sensitive fluorescent polarization assay.


Exploring the chemical space of influenza neuraminidase inhibitors.
The fight against the emergence of mutant influenza strains has led to the screening of an increasing number of compounds for inhibitory activity against influenza neuraminidase. This study explores the chemical space of neuraminidase inhibitors (NAIs), which provides an opportunity to obtain further molecular insights regarding the underlying basis of their bioactivity. In particular, a large set of 347 and 175 NAIs against influenza A and B, respectively, was compiled from the literature. Molecular and quantum chemical descriptors were obtained from low-energy conformational structures geometrically optimized at the PM6 level. The bioactivities of NAIs were classified as active or inactive according to their half maximum inhibitory concentration (IC50) value in which IC50 < 1µM and ≥ 10µM were defined as active and inactive compounds, respectively. Interpretable decision rules were derived from a quantitative structure-activity relationship (QSAR) model established using a set of substructure descriptors via decision tree analysis. Univariate analysis, feature importance analysis from decision tree modeling and molecular scaffold analysis were performed on both data sets for discriminating important structural features amongst active and inactive NAIs. Good predictive performance was achieved as deduced from accuracy and Matthews correlation coefficient values in excess of 81% and 0.58, respectively, for both influenza A and B NAIs. Furthermore, molecular docking was employed to investigate the binding modes and their moiety preferences of active NAIs against both influenza A and B neuraminidases. Moreover, novel NAIs with robust binding fitness towards influenza A and B neuraminidase were generated via combinatorial library enumeration and their binding fitness was on par or better than FDA-approved drugs. The results from this study are anticipated to be beneficial for guiding the rational drug design of novel NAIs for treating influenza infections.


Self-assembly of ordered nanowires in biological suspensions of single-wall carbon nanotubes.
We investigate the self-assembly of ordered nanowires from length-purified single-wall carbon nanotubes (SWCNTs) in aqueous suspensions of the biological surfactant sodium deoxycholate. Macroscopically straight and nearly periodic linear arrangements of aligned individual SWCNTs are found to self-assemble in two-dimensional geometries from nanotube suspensions that are otherwise stable in the bulk, which we attribute to a dominance of surface effects under strong confinement. Directed self-assembly is explored through surface patterning, opening up new potential routes to nanotube manipulation for optical diagnostics and applications that require ordered arrangements of mutually aligned SWCNTs. The stability of these structures to thermal fluctuations and changes in solution chemistry are surveyed with near-infrared fluorescence microscopy.


OCCURRENCE OF GRAM-POSITIVE ORGANISMS POSSESSING CHARACTERISTICS SIMILAR TO THOSE OF SALMONELLA AND THE PRACTICAL PROBLEM OF RAPID AND DEFINITIVE SALMONELLA IDENTIFICATION.
The occurrence and incidence of gram-positive organisms which possess some biochemical and serological characteristics in common with salmonellae are described. These organisms were encountered as contaminants in various food products as well as in feces. Their growth in various Salmonella enrichment media, typical Salmonella-like growth on differential selective media, biochemical similarities to Salmonella, and agglutination in Salmonella polyvalent O antiserum serve as a source of possible confusion in analyses for Salmonella. Although a definitive identification was not performed, preliminary results indicate that these bacteria closely resemble members of the genus Brevibacterium. No sanitary significance could be associated with these bacteria, because they were never found to coexist with Salmonella. The occurrence of these bacteria illustrates the pitfalls of a cursory examination for Salmonella. On the premise that ultimate identification of Salmonella rests upon serological procedures, a rapid and definitive identification of suspect Salmonella isolates is proposed, based upon reactions with polyvalent group O, group O, and Spicer-Edwards H antisera.


Knowledge and Beliefs about Dengue Transmission and Their Relationship with Prevention Practices in Hermosillo, Sonora.
Dengue is an emerging threat in the U.S.-Mexico border region. Transmission has regularly occurred in Sonora, MX since 1982 but it was not until 2014 that cities directly on the Arizona-Sonora border had local transmission. One of the closest urban areas to have regular seasonal transmission is Hermosillo, SN, MX. Developing a better understanding of the knowledge and perceptions of dengue in close geographic proximity to the border can identify areas to target for prevention and control measures. We conducted focus groups in six neighborhoods in Hermosillo, SN, MX; three with high-dengue transmission and three with lower transmission. Awareness of dengue and experience with dengue was common. In all focus groups, discussants reported knowing someone personally who had past dengue infection. We further identified several key ways that the perceptions of dengue transmission could influence the effectiveness of dengue control campaigns. First, there was confusion about how dengue is transmitted. While people associated dengue with mosquitoes, multiple modes of transmission were perceived including direct person-to-person transmission. In one focus group, discussants indicated a stigma surrounding dengue infection. The necessity to maintain cleanliness in their households was identified as a primary strategy to fight dengue; however, participants also noted the limited impact and their actions may have on transmission if there is lack of community support or governmental infrastructure to control neighboring and public spaces. As dengue risk increases in the border region, more efforts should be made to clearly convey the single mode of transmission of dengue to avoid the development of stigma. More coordinated efforts should be made to not only control but also prevent dengue.


Unusual Initial Abdominal Presentations of Invasive Meningococcal Disease.
Invasive meningococcal disease (IMD) is recognized as septicemia and/or meningitis. However, early symptoms may vary and are frequently nonspecific. Early abdominal presentations have been increasingly described. We aimed to explore a large cohort of patients with initial abdominal presentations for association with particular meningococcal strains. Confirmed IMD cases in France between 1991 and 2016 were screened for the presence within the 24 hours before diagnosis of at least 1 of the following criteria (1) abdominal pain, (2) gastroenteritis with diarrhea and vomiting, or (3) diarrhea only. Whole-genome sequencing was performed on all cultured isolates. We identified 105 cases (median age, 19 years) of early abdominal presentations with a sharp increase since 2014. Early abdominal pain alone was the most frequent symptom (n = 67 [64%]), followed by gastroenteritis (n = 26 [25%]) and diarrhea alone (n = 12 [11%]). Twenty patients (20%) had abdominal surgery. A higher case fatality rate (24%) was observed in these cases compared to 10.4% in all IMD in France (P = .007) with high levels of inflammation markers in the blood. Isolates of group W were significantly more predominant in these cases compared to all IMD. Most of these isolates belonged to clonal complex 11 of the sublineages of the South American-UK strain. Abdominal presentations are frequently provoked by hyperinvasive isolates of meningococci. Delay in the management of these cases and the virulence of the isolates may explain the high fatality rate. Rapid recognition is a key element to improve their management.


Delayed dispersal and prolonged brood care in a family-living beetle.
Delayed juvenile dispersal is an important prerequisite for the evolution of family-based social systems, such as cooperative breeding and eusociality. In general, young adults forego dispersal if there are substantial benefits to remaining in the natal nest and/or the likelihood of dispersing and breeding successfully is low. We investigate some general factors thought to drive delayed juvenile dispersal in the horned passalus beetle, a family-living beetle in which young adults remain with their families in their natal nest for several months before dispersing. Fine-scale population genetic structure indicated high gene flow between nest sites, suggesting that constraints on mobility are unlikely to explain philopatry. Young adults do not breed in their natal log and likely disperse before reaching breeding age, suggesting that they do not gain direct reproductive benefits from delayed dispersal. We also examined several ways in which parents might incentivize delayed dispersal by providing prolonged care to adult offspring. Although adult beetles inhibit fungal growth in the colony by manipulating both the nest site and deceased conspecifics, this is unlikely to be a major explanation for family living as both parents and adult offspring seem capable of controlling fungal growth. Adult offspring that stayed with their family groups also neither gained more mass nor experienced faster exoskeleton development than those experimentally removed from their families. The results of these experiments suggest that our current understanding of the factors underlying prolonged family living may be insufficient to explain delayed dispersal in at least some taxa, particularly insects.


[Clinical aspects and long-term prognosis of spontaneous thalamus hematomas].
In 47 cases with thalamic hemorrhage the estimated volume and the extension of the hematoma was compared to clinical data. The critical blood volume above which the mortality rate markedly increased was 10 cc. The most unfavourable outcome was found in hematomas extending to the midbrain or causing extensive ventricular hemorrhage. The severity and characteristics of the neurological deficit depended on the extension of the hematoma as well. Aphasia was a common feature when the thalamic hemorrhage occurred in the dominant hemisphere. Thalamic syndrome and ocular abnormalities were rare. The mortality rate was 17% and increased to 32% within the limits of twelve months. After a mean observation period of 31 months over 60% of the survivors had no or minimal disabilities. Only 20% remained seriously handicapped. The degree of the remaining disabilities depended on the original blood-volume. Eighteen of 32 survivors were submitted to neuropsychological tests. Three patients had an amnestic syndrome.


Catastrophic Head Injuries in High School and Collegiate Sports.
OBJECTIVE: To describe the incidence of catastrophic head injuries in a variety of high school and college sports. DESIGN AND SETTING: Data on catastrophic head injuries were compiled in a national surveillance system maintained by the National Center for Catastrophic Sports Injury Research. The data were compiled with the assistance of coaches, athletic trainers, athletic directors, executive officers of state and national athletic organizations, a national newspaper clipping service, professional associates of the researchers, and national sport organizations. SUBJECTS: Data included all high school and college athletic programs in the United States. MEASUREMENTS: Background information on the athlete (age, height, weight, experience, previous injury, etc), accident information, immediate and postaccident medical care, type of injury, and equipment involved. Autopsy reports were used when available. RESULTS: A football-related fatality has occurred every year from 1945 through 1999, except for 1990. Head-related deaths accounted for 69% of football fatalities, cervical spinal injuries for 16.3%, and other injuries for 14.7%. High school football produced the greatest number of football head-related deaths. From 1984 through 1999, 69 football head-related injuries resulted in permanent disability. Sixty-three of the injuries were associated with high school football and 6 with college football. Although football has received the most attention, other sports have also been associated with head-related deaths and permanent disability injuries. From 1982 through 1999, 20 deaths and 19 permanent disability injuries occurred in a variety of sports. Track and field, baseball, and cheerleading had the highest incidence of these catastrophic injuries. Three deaths and 3 injuries resulting in permanent disability have occurred in female participants. CONCLUSIONS/RECOMMENDATIONS: Reliable data collection systems and continual analysis of the data can help us to reduce the number of catastrophic head-related injuries. I include additional recommendations for injury prevention.


Alpha6-integrin is expressed on germinal centre B cells and modifies growth of a B-cell line.
The production of high-affinity antibodies requires diversification of the antibody repertoire by somatic hypermutation followed by selection of those B cells bearing the highest affinity antibodies. Whilst many surface molecules that mediate the cell-cell interactions required for germinal centre formation have been identified, little is known of the importance of interactions with components of the extracellular matrix, i.e. fibronectin, collagen and laminin. We demonstrate that the laminin-binding alpha6-integrin is expressed on germinal centre B cells and is induced during the in vitro activation of naïve splenic B cells. A laminin network is demonstrated within the germinal centre. Analysis of an alpha6-integrin-expressing mouse B-cell line, A20, demonstrates that this molecule is essential for binding to laminin, and that blocking by anti-alpha6-integrin immunoglobulin causes loss of adhesion associated with an increase in proliferation. There is no correlation with changes in BCL-6 or Blimp-1 expression, suggesting that alpha6-integrin does not play a role in differentiation.


Homelessness and severe mental illness in low- and middle-income countries: scoping review.
Despite being a global problem, little is known about the relationship between severe mental illness (SMI) and homelessness in low- and middle-income countries (LMICs). Homeless people with SMI are an especially vulnerable population and face myriad health and social problems. In LMICs, low rates of treatment for mental illness, as well as differing family support systems and cultural responses to mental illness, may affect the causes and consequences of homelessness in people with SMI. To conduct a systematic, scoping review addressing the question: what is known about the co-occurrence of homelessness and SMI among adults living in LMICs? We conducted an electronic search, a manual search and we consulted with experts. Two reviewers screened titles and abstracts, assessed publications for eligibility and appraised study quality. Of the 49 included publications, quality was generally low: they were characterised by poor or unclear methodology and reporting of results. A total of 7 publications presented the prevalence of SMI among homeless people; 12 presented the prevalence of homelessness among those with SMI. Only five publications described interventions for this population; only one included an evaluation component. Evidence shows an association between homelessness and SMI in LMICs, however there is little information on the complex relationship and direction of causality between the phenomena. Existing programmes should undergo rigorous evaluation to identify key aspects required for individuals to achieve sustainable recovery. Respect for human rights should be paramount when conducting research with this population. None.


The effect of maternal flora on Candida colonisation in the neonate.
Colonisation may be the first step for the development of Candida infection. The source of neonatal colonisation is thought to be the hospital environment or the maternal vaginal tract. This study investigated to what extend Candida isolates in neonates are similar to isolates from their mother's vaginal tract. Vaginal samples were collected from 347 pregnant women within 48 h before delivery. Samples from oral and rectal mucosa of their neonates were collected within 24-72 h after delivery, were cultured and yeast species were identified. Antifungal susceptibility tests against six antifungal agents were performed. All paired isolates from mother and infant were genotyped by pulse field gel electrophoresis. A total of 82 mothers and of 16 infants were found colonised by Candida spp. C. albicans was the most common species in pregnant women (n = 68) followed by C. glabrata (n = 11). Only C. albicans was isolated from infants, mainly (14/16) from rectal site. All colonised neonates were born to mothers colonised by C. albicans. Candida genotyping revealed identical strains in all investigated neonate-mother pairs. All isolates were susceptible to amphotericin B. Our findings strongly suggest that vertical transmission has the principal role in the neonatal colonisation by C. albicans in the very first days of life.


Clinical evaluation of antiviral combination treatment in cats with feline herpesvirus-1 infection.
Feline herpesvirus-1 (FHV-1) can cause lifelong problems such as rhinotracheitis and ocular disease due to latency and reactivation in affected cats. The particular effects of antiviral drugs have been separately investigated in previous studies for decades and little is known about the combination treatment in active FHV-1 infection. Therefore, we aimed to evaluate the effects of antiviral combination on clinical effectiveness in cats with naturally occurring FHV-1 infection. 28 cats suffering from clinical signs of sneezing, nasal congestion, conjunctivitis, and eye/nose discharge were involved in this study following FHV-1 DNA detection by PCR assay in oculo-oropharyngeal samples. The treatment protocol was as follows: oral famciclovir and L-lysine, ophthalmic acyclovir, and subcutaneous amoxicillin plus clavulanic acid. The symptoms improved each day and total recovery success rate was 80% reduction in clinical scores at the end of the treatment on day 10 (p<0.001). Additionally, PCR was found to be negative for FHV-1 DNA in 82.1% of the samples after the treatment. There were mild decreases in neutrophil and monocyte counts (p>0.05). The arginine to lysine ratio decreased in favour of lysine (p<0.01). As a result, the antiviral combination treatment with famciclovir, L-lysine and ophthalmic acyclovir, and antibacterial drug appears to be clinically effective for the treatment of naturally occurring active FHV-1 infection in cats. In addition, any adverse clinical effect has not been determined associated with the antiviral combination during the study.


Lamivudine therapy for spontaneously occurring severe acute exacerbation in chronic hepatitis B virus infection: a preliminary study.
The nucleoside analogue lamivudine, a potent inhibitor of hepatitis B virus replication, has shown notable results in treating chronic hepatitis B. However, lamivudine has not been specifically tested for effectiveness against spontaneously occurring severe acute exacerbations of hepatitis in patients chronically infected with this virus. We addressed this issue in a pilot study. Ten patients with chronic hepatitis B developed severe acute exacerbation spontaneously during follow-up; 3 of them developed hepatic failure shortly before entering the trial. Lamivudine was administered long-term to the 10 patients at a daily oral dose of 100 or 300 mg. All 3 patients with hepatic failure at initiation of treatment recovered dramatically. Of the remaining 7 patients, 5 recovered rapidly with lamivudine, but 2 progressed quickly to hepatic failure despite treatment. One died of sepsis and the other of multiorgan failure. In the 8 survivors, serum alanine transaminase activity decreased rapidly to normal with lamivudine therapy, and serum hepatitis B virus DNA level declined rapidly to undetectable levels. Serum total bilirubin concentrations normalized somewhat later. Prothrombin time improved steadily and gradually. Hepatitis B e antigen elimination or seroconversion was achieved in 3 survivors. No adverse effects were noted in any patient. All survivors had good quality of life with long-term lamivudine monotherapy. Lamivudine is effective, safe, and well tolerated by patients with spontaneous, severe, acute exacerbation complicating chronic hepatitis B virus infection, even in the presence of hepatic failure. Lamivudine appears to be an attractive therapeutic option and may represent the best choice.


Role for putative hepatocellular carcinoma stem cell subpopulations in biological response to incomplete thermal ablation: in vitro and in vivo pilot study.
To investigate the potential role for CD44(+) and CD90(+) hepatocellular carcinoma (HCC) cellular subpopulations in biological response to thermal ablation-induced heat stress. This study was approved by the institutional animal care committee. The N1S1 rat HCC cell line was subjected to sublethal heat stress (45 °C) or control (37 °C) for 10 min, costained with fluorescent-labeled antibodies against CD44, CD90, and 7-AAD after a 48-h recovery and analyzed by flow cytometry to assess the percentage of live CD44(+) and CD90(+) HCC cells (n = 4). Experiments were repeated with pretreatment of N1S1 cells with a dose titration of the dual PI3K-mTOR inhibitor BEZ235 or vehicle control (n = 3). Rats bearing orthotopic N1S1 tumors were subjected to ultrasound-guided partial laser ablation (n = 5) or sham ablation (n = 3), euthanized 24 h after ablation, and liver/tumor analyzed for immunohistochemical staining of CD44 and CD90. Differences between groups were compared with an unpaired t test. Sublethal heat stress induced a significant increase in the relative proportion of live CD44(+) and CD90(+) HCC cells compared to the control group: CD44(+)CD90(-) (5.3-fold; p = 0.0001), CD44(-)CD90(+) (2.4-fold; p = 0.003), and CD44(+)CD90(+) (22.0-fold; p < 0.03). Inhibition of PI3K-mTOR prevented heat stress-induced enrichment of the population of live CD44(+) HCC cells (p < 0.01), but not CD90(+) cells (p > 0.10). Immunohistochemical analysis demonstrated preferential localization of clusters of CD44(+) cells at both the tumor margin and ablation margin. These studies provide experimental evidence supporting a role for HCC cells expressing the putative stem cell marker CD44 in HCC response to heat stress.


Long-term effect of a chicken-based diet versus enalapril on albuminuria in type 2 diabetic patients with microalbuminuria.
In short-term studies, the replacement of red meat in the diet with chicken reduced the urinary albumin excretion rate (UAER) and improved lipid profile in type 2 diabetic patients with diabetic nephropathy. The present study sought to assess these effects over a long-term period, comparing the effects of a chicken-based diet (CD) versus enalapril on renal function and lipid profile in microalbuminuric type 2 diabetic patients. This was a randomized, open-label, controlled clinical trial with a follow-up of 1 year. The trial involved outpatients with type 2 diabetes attending a clinic of the Division of Endocrinology at a tertiary-care hospital. Twenty-eight microalbuminuric patients completed the study and were evaluated. Patients were randomized to an experimental diet (CD plus active placebo) or to treatment with enalapril (10 mg/day plus usual diet). The main outcome measure was UAER (according to immunoturbidimetry). Blood pressure, anthropometric indices, and compliance were also evaluated monthly. The glomerular filtration rate ((51)Cr-EDTA), and lipid, glycemic, and nutritional indices, were measured at baseline and quarterly. The UAER was reduced after CD (n = 13; from 62.8 [range, 38.4 to 125.1] to 49.1 [range, 6.2 to 146.5] microg/min; P < .001) and after enalapril (n = 15; from 55.8 [range, 22.6 to 194.3] to 23.1 [range, 4.0 to 104.9] microg/min; P < .001), and this was already significant at month 4. The reduction in UAER after CD (32%; 95% confidence interval, 6.7% to 57.6%) and after enalapril treatment (44.7%; 95% confidence interval, 28.3% to 61.1%; P = .366) were not significantly different. The CD and the angiotensin-converting enzyme inhibitor enalapril promoted a similar reduction of UAER in patients with type 2 diabetes and microalbuminuria in a 12-month follow-up period.


Human DMTF1β antagonizes DMTF1α regulation of the p14(ARF) tumor suppressor and promotes cellular proliferation.
The human DMTF1 (DMP1) transcription factor, a DNA binding protein that interacts with cyclin D, is a positive regulator of the p14ARF (ARF) tumor suppressor. Our earlier studies have shown that three differentially spliced human DMP1 mRNAs, α, β and γ, arise from the human gene. We now show that DMP1α, β and γ isoforms differentially regulate ARF expression and promote distinct cellular functions. In contrast to DMP1α, DMP1β and γ did not activate the ARF promoter, whereas only β resulted in a dose-dependent inhibition of DMP1α-induced transactivation of the ARF promoter. Ectopic expression of DMP1β reduced endogenous ARF mRNA levels in human fibroblasts. The DMP1β- and γ-isoforms share domains necessary for the inhibitory function of the β-isoform. That DMP1β may interact with DMP1α to antagonize its function was shown in DNA binding assays and in cells by the close proximity of DMP1α/β in the nucleus. Cells stably expressing DMP1β, as well as shRNA targeting all DMP1 isoforms, disrupted cellular growth arrest induced by serum deprivation or in PMA-derived macrophages in the presence or absence of cellular p53. DMP1 mRNA levels in acute myeloid leukemia samples, as compared to granulocytes, were reduced. Treatment of acute promyelocytic leukemia patient samples with all-trans retinoic acid promoted differentiation to granulocytes and restored DMP1 transcripts to normal granulocyte levels. Our findings imply that DMP1α- and β-ratios are tightly regulated in hematopoietic cells and DMP1β antagonizes DMP1α transcriptional regulation of ARF resulting in the alteration of cellular control with a gain in proliferation.


Cold spots are universal in protein-protein interactions.
Proteins interact with each other through binding interfaces that differ greatly in size and physico-chemical properties. Within the binding interface, a few residues called hot spots contribute the majority of the binding free energy and are hence irreplaceable. In contrast, cold spots are occupied by suboptimal amino acids, providing possibility for affinity enhancement through mutations. In this study, we identify cold spots due to cavities and unfavorable charge interactions in multiple protein-protein interactions (PPIs). For our cold spot analysis, we first use a small affinity database of PPIs with known structures and affinities and then expand our search to nearly 4000 homo- and heterodimers in the Protein Data Bank (PDB). We observe that cold spots due to cavities are present in nearly all PPIs unrelated to their binding affinity, while unfavorable charge interactions are relatively rare. We also find that most cold spots are located in the periphery of the binding interface, with high-affinity complexes showing fewer centrally located colds spots than low-affinity complexes. A larger number of cold spots is also found in non-cognate interactions compared to their cognate counterparts. Furthermore, our analysis reveals that cold spots are more frequent in homo-dimeric complexes compared to hetero-complexes, likely due to symmetry constraints imposed on sequences of homodimers. Finally, we find that glycines, glutamates, and arginines are the most frequent amino acids appearing at cold spot positions. Our analysis emphasizes the importance of cold spot positions to protein evolution and facilitates protein engineering studies directed at enhancing binding affinity and specificity in a wide range of applications.


The Therapeutic Potential of Anthocyanins: Current Approaches Based on Their Molecular Mechanism of Action.
Anthocyanins are natural phenolic pigments with biological activity. They are well-known to have potent antioxidant and antiinflammatory activity, which explains the various biological effects reported for these substances suggesting their antidiabetic and anticancer activities, and their role in cardiovascular and neuroprotective prevention. This review aims to comprehensively analyze different studies performed on this class of compounds, their bioavailability and their therapeutic potential. An in-depth look in preclinical, in vitro and in vivo, and clinical studies indicates the preventive effects of anthocyanins on cardioprotection, neuroprotection, antiobesity as well as their antidiabetes and anticancer effects.


Software solutions for the livestock genomics SNP array revolution.
Since the beginning of the genomic era, the number of available single nucleotide polymorphism (SNP) arrays has grown considerably. In the bovine species alone, 11 SNP chips not completely covered by intellectual property are currently available, and the number is growing. Genomic/genotype data are not standardized, and this hampers its exchange and integration. In addition, software used for the analyses of these data usually requires not standard (i.e. case specific) input files which, considering the large amount of data to be handled, require at least some programming skills in their production. In this work, we describe a software toolkit for SNP array data management, imputation, genome-wide association studies, population genetics and genomic selection. However, this toolkit does not solve the critical need for standardization of the genotypic data and software input files. It only highlights the chaotic situation each researcher has to face on a daily basis and gives some helpful advice on the currently available tools in order to navigate the SNP array data complexity.


[Rapidly cycling bipolar disorders].
Rapid cyclers are defined by the occurrence of four or more mood episodes during the previous 12 months. Clinical, epidemiological and population characteristics of these patients are presented as well as studies that validate them. Hypotheses and theoretical models allowing their analysis are reviewed. The last part of the paper deals with treatments.


Bacteriophage Control of Infectious Biofilms.
Biofilm formation, a strategy of bacterial survival, is a significant concern in different areas, including health, where infectious biofilms are very difficult to combat with conventional antimicrobial therapies. Bacteriophages, the viruses that infect bacteria, are promising agents to prevent and control biofilm-related infections. This chapter describes a series of standard procedures that can be used to study the potential of bacteriophages for biofilm control, from biofilm formation to bacteriophage treatment and evaluation of its efficacy.


Iberian wild leporidae as hosts of zoonotic enteroparasites in Mediterranean ecosystems of Southern Spain.
Wild lagomorphs including rabbits and hares can act as natural carriers or reservoirs of bacterial and parasitic zoonotic diseases. However, little is known on the epidemiology and potential public health significance of intestinal eukaryotes in wild leporids. We examined faecal samples from European wild rabbits (Oryctolagus cuniculus, n = 438) and Iberian hares (Lepus granatensis, n = 111) collected in the Autonomous Region of Andalusia in southern Spain during 2012-2021. We searched for the presence of DNA from the main intestinal protist and microsporidial pathogens of veterinary and public health concerns using molecular methods (PCR followed by Sanger and next-generation sequencing). Giardia duodenalis was the most prevalent species found (27.8%, 153/550; 95% CI: 24.1-31.8), followed by Cryptosporidium spp. (1.3%, 7/550; 95% CI: 0.5-2.6), Blastocystis sp. (1.1%, 6/550; 95% CI: 0.4-2.4) and Encephalitozoon intestinalis (0.2%, 1/550; 95% CI: 0.0-10.1). All samples tested negative for Enterocytozoon bieneusi. Sequence analyses revealed the presence of sub-assemblage BIV (n = 1) within G. duodenalis, and Cryptosporidium cuniculus (n = 6) and Cryptosporidium andersoni (n = 1) within Cryptosporidium. The presence of ruminant-adapted C. andersoni is indicative of a potential cross-species transmission event, although a spurious infection (mechanical carriage) cannot be ruled out. Samples assigned to C. cuniculus belonged to the gp60 subtype families Va (n = 3) and Vb (n = 2). The six Blastocystis-positive samples were identified as ST2 (n = 3) and ST1 + ST2 (n = 3). Our molecular results suggest that wild rabbits and hares were primarily infected by leporid-adapted species of eukaryotic pathogens. However, the occasional findings of zoonotic G. duodenalis sub-assemblage BIV, Blastocystis sp. ST1 and ST2, and Encephalitozoon intestinalis could be of public health relevance.


Identification of Bioactive Peptides from Cereal Storage Proteins and Their Potential Role in Prevention of Chronic Diseases.
Cereal grains, such as wheat, barley, rice, rye, oat, millet, sorghum, and corn, have been staples in human diets since ancient times. At present, there is a significant body of scientific evidence showing the health benefits of consuming whole grains in chronic disease prevention, particularly in regards to diabetes, cardiovascular disease, and cancer. The objective was to determine bioactive peptides in cereal grains that may prevent cardiovascular disease, cancer, inflammation, and diabetes. Bioactive peptides that may be obtained from cereal grains, particularly wheat, oat, barley, and rice, were identified. Bioactive peptides that play a role in chronic disease prevention have been found primarily in legumes and dairy products; although research connecting cereal grains with potential bioactive peptide activity is limited. In this review, 4 cereal grains, wheat, oat, barley, and rice, were evaluated for bioactive peptide potential using the BIOPEP database. In addition, research information was compiled for each grain regarding evidence about the effect of their proteins in prevention of chronic diseases. All 4 grains showed high occurrence frequencies of angiotensin-converting enzyme-inhibitor peptides (A = 0.239 to 0.511), as well as of dipeptidyl peptidase-inhibitor and antithrombotic, antioxidant, hypotensive, and opioid activity. Wheat and rice proteins had anticancer sequences present. Wheat and barley showed the greatest diversity and abundance of potential biological activity among the cereal proteins. Further research needs to be conducted to learn how these biologically active peptide sequences are released from cereal grains. This study supports the notion that cereal grains are a nutritious part of a healthy diet by preventing chronic diseases.


[Definition, classification and epidemiology of whiplash].
A whiplash trauma is caused by an acceleration-deceleration force transferring its energy to the cervical spine. Whiplash-associated disorder (WAD) refers to the symptoms that develop after a whiplash injury. The prognosis is favorable with recovery in over 90% of the injured subjects. In a fraction of patients, long-term symptoms with pain and cognitive and emotional symptoms may occur, causing long-term disability. The pathophysiology is unclear. Most research groups favor a multifactorial pathophysiology similar to that observed for other chronic pain conditions without a clear nociceptive or neuropathic component.


Diagnosis of Fasciola hepatica infection in beef calves by plasma enzyme analysis.
Plasma analysis for albumin, total bilirubin, and total protein values and aspartate aminotransferase (AST), arginase, and gamma-glutamyl transpeptidase (GGT) activities was used for the early and quantitative diagnosis of experimental Fasciola hepatica infections in beef calves. Calves were infected on 3 occasions with 1,000 (n = 5), 100 (n = 5), or 10 (n = 4) metacercariae for a total infective dose of 3,000, 300, or 30, respectively. Albendazole (15 mg/kg of body weight) was administered to 7 infected calves on postinfection (initial) week (PIW) 13. All calves were euthanatized and necropsied on PIW 16 for the determination of fluke infections. Plasma constituents were determined weekly. Significant (P less than 0.05) increases in AST activity occurred as early as PIW 4 and GGT activity at PIW 9, as compared with that in noninfected controls. Fluke burden-related differences were observed in GGT activity from PIW 9 onward. Increases in AST activity reflected parenchymal liver damage, whereas increases in GGT reflected hepatobiliary damage; therefore, differentiation could be made between the migratory and ductal phases of the infection. There was no correlation between arginase activity and fluke infection. As compared with fecal examination results, plasma enzyme analysis gave an earlier and semiquantitative indication of F hepatica infection in experimentally infected calves. Although increases in these plasma constituents were not definitely diagnostic of fascioliasis, useful information on the size of the fluke burden and progress of the disease process could be obtained by these methods. Plasma enzyme analyses of AST and GGT were not indicative of chemotherapeutic success or failure when calves with mature F hepatica (14 weeks old) infections were treated.


Leukocytapheresis for rheumatic disease.
Leukocytapheresis (LCAP) is an apheresis technique for depleting pathogenic leukocytes from the circulating blood to improve the condition of the patient. LCAP sensu lato has been applied for the treatment of various rheumatic diseases: other treatments include thoracic duct drainage, photopheresis, centrifugal LCAP, granulocytapheresis (GCAP) and filtration LCAP. Among these modalities, GCAP and filtration LCAP are most commonly used in Japan for two reasons; the equipment and procedure are simple and practical and adverse events are rare and minor. In this article, LCAP, in particular filtration LCAP, for the treatment of rheumatic diseases is reviewed.