Protective effect of chlormethiazole, a sedative, against acetaminophen-induced liver injury in mice.
The hepatotoxicity of acetaminophen is not a result of the parent compound but is mediated by its reactive metabolite N-acetyl-p-benzoquinone imine. Cytochrome P4502E1 (CYP2E1) is the principal enzyme of this biotransformation, which accounts for approximately 52% of the bioactivation in human microsomes. Recently, chlormethiazole a sedative drug, is reported to be an efficient inhibitor of CYP2E1 activity in human beings. In this study we wished to evaluate whether chlormethiazole, an inhibitor of CYP2E1, could prevent acetaminophen-induced liver injury in mice. Acetaminophen, at doses ranging from 200 to 600 mg/kg, was injected into the peritoneum of female C57BL/6 inbred mice fasted for four hours. Chlormethiazole (60 mg/kg) or 5% dextrose water was given 30 min before or 2 h after acetaminophen. Serum aminotransferase activities, histologic index score, survival rate and hepatic malondialdehyde levels were compared. Pretreatment with chlormethiazole 30 min before 400 mg/kg of acetaminophen completely inhibited acetaminophen-induced liver injury (median 118.5 U/L, range 75 to 142 vs. 14,070 U/L, range 5980 to 27,680 for AST; 49 U/L, range 41 to 64 vs. 15,330 U/L, range 13,920 to 15,940 for ALT). In mice receiving chlormethiazole 2 h after acetaminophen, the mean AST and ALT levels were also less elevated, reaching only 20% of the value of acetaminophen-only group. These protective effects were confirmed histologically. Whereas more than 50% of mice died at 500 mg/kg of acetaminophen, all the mice pretreated with chlormethiazole survived at the same dose. Chlormethiazole effectively reduces acetaminophen-induced liver injury in mice. Further studies are needed to assess its role in humans.


Concentric Isokinetic Strengthening Program's Impact on Knee Biomechanical Parameters, Physical Performance and Quality of Life in Overweight/Obese Women with Chronic Meniscal Lesions.
Meniscal injuries are one of the most common intra-articular knee injuries. Different treatments are presented depending on the symptoms and duration of meniscus tears, such as arthroscopic partial meniscectomy, physiotherapy, or even pharmacological treatment. The purpose was to investigate the effect of a concentric isokinetic knee muscle strengthening program on strength, joint range of motion, physical performance, quality of life and pain tolerance in overweight/obese women with chronic meniscal lesions. Twenty-four overweight/obese women were randomized into two groups. A control group (CG) performed a usual rehabilitation program plus isokinetic muscle strengthening (IMS) in the continuous passive motion mode and measured with an isokinetic dynamometer. An experimental group (EG) performed the same program in combination with IMS in the isokinetic active mode. The peak torque of the knee extensors (PTE) and flexors (PTF), sit-to-stand test, stair climb test, joint amplitude, heel-to-buttock distance, Thessaly test, KOOS questionnaire of pain and quality of life were measured pre- and post-protocol. After the intervention, the sit-stand number for both groups was significantly higher (p < 0.001) and the time to climb stairs was significantly reduced for the EG (p < 0.001). A significant improvement in joint range of motion, life quality (p < 0.001), relief in knee pain (p < 0.001) and in the post-program evaluation at the EG (p < 0.05) was noted. There was no significant difference in PTE and PTF between groups at 60°/s and 180°/s. The IMS in the active mode could be an effective therapeutic modality in managing middle-aged patients suffering from a degenerative meniscal tear.


[Sex differences in body image, weight control and Body Mass Index of Spanish adolescents].
Sex differences in body image, weight control and Body Mass Index of Spanish adolescents. This research paper studied the differences among 21,811 adolescents (between the ages of 11 and 18) in key variables in the development of eating disorders, including the Body Mass Index, the perception of and satisfaction with their body image, and the behaviours used to control weight. In spite of the fact that the girls had a better adjusted BMI and a lesser degree of overweight and obesity, we found that they perceived themselves as being fatter, were less satisfied with body image, and the ones who dieted the most to lose weight. On the other hand, we found that the main reason for boys and girls to diet in an effort to lose weight was not their real body weight, but rather their perception of their own bodies, followed by just how satisfied they were with their bodies. Therefore, important differences are revealed between boys and girls in this article, which must be taken into consideration in the design and development of the various programs that are aimed at the prevention of problems with body image and diet behaviour.


Respiratory pathophysiology with seizures and implications for sudden unexpected death in epilepsy.
There is increasing evidence that periictal respiratory disturbances are an important contributor to the pathophysiological changes leading to sudden unexpected death in epilepsy (SUDEP). In patients with SUDEP occurring in epilepsy monitoring units, respiratory disturbances occurred early in the postictal period and frequently preceded terminal bradycardia and asystole. Periictal hypoxemia and hypercapnia are observed in about one-third of patients undergoing video-EEG telemetry. Pulmonary edema is frequently observed at autopsy in cases of SUDEP and may be relevant as a contributing cause in a subset of SUDEP. Animal studies support the notion that periictal respiratory disturbances are crucial to the pathophysiology of SUDEP. Serotonergic neurons modulate the excitability of the neuronal network generating the respiratory rhythm. Ictal and periictal impairment of serotonergic and glutaminergic neurons involved in the arousal system may also predispose to SUDEP by impeding the patient's ability to reposition the head and facilitate ventilation after a seizure. Periictal functional impairment of serotonergic neurons seems to be important in the pathophysiology of SUDEP and a potential target for pharmacotherapy aimed at SUDEP risk reduction.


Outcomes of Elective Induction of Labor versus Expectant Management among Obese Women at ≥39 Weeks.
Maternal obesity is associated with many adverse obstetric outcomes including cesarean delivery. It is unclear whether induction of labor can reduce these risks. Previous studies report conflicting results on the outcomes of elective induction of labor among obese women. This study aimed to compare maternal and neonatal outcomes between obese women undergoing elective induction of labor and those undergoing expectant management at ≥39 weeks. This was a retrospective cohort study from the Consortium on Safe Labor of obese women (defined by prepregnancy body mass index≥ 30kg/m2) with singleton gestations at ≥39 weeks without medical comorbidities from 2002 through 2008. Women scheduled for medically indicated induction of labor were excluded. The primary outcome of cesarean delivery was compared between obese women undergoing elective induction of labor and expectant management during 39th, 40th, and 41st weeks using univariable and multivariable analyses, stratifying by parity. In all, 7,298 nulliparous and 9,789 parous women were eligible for analysis. After controlling for potential confounders, elective induction of labor during 39th week in nulliparous and parous women was associated with lower odds of cesarean delivery (39.1 vs. 41.6%, adjusted odds ratio [OR]: 0.47, 95% confidence interval [CI]: 0.30-0.74 for nulliparous and 5.5 vs. 10.1%, adjusted OR: 0.34, 95% CI: 0.20-0.61 for parous women) compared with expectant management. Elective induction of labor during 40th and 41st weeks was not associated with lower odds of cesarean delivery. In addition, macrosomia was reduced in nulliparous women undergoing elective induction of labor during the 40th week (12.1 vs. 18.5%, adjusted OR: 0.56, 95% CI: 0.35-0.87) and in parous women undergoing elective induction of labor during 39th (11.6 vs. 17.6%, adjusted OR: 0.50, 95% CI: 0.38-0.66) and 40th weeks (16.4 vs. 22.2%, adjusted OR: 0.53, 95% CI: 0.36-0.78). Elective induction of labor at 39 weeks, when compared with expectant management, was associated with lower cesarean deliveries in obese nulliparous and parous women.


Blunted Ventral Striatum Development in Adolescence Reflects Emotional Neglect and Predicts Depressive Symptoms.
Emotional neglect is associated with multiple negative outcomes, particularly increased risk for depression. Motivated by increasing evidence of reward-related ventral striatum (VS) dysfunction in depression, we investigated the role of developmental changes in VS activity on the emergence of depressive symptomatology as a function of emotional neglect. We examined relationships between longitudinal neuroimaging of reward-related VS activity, assessments of mood, and measures of emotional neglect in 106 participants first scanned between ages 11 to 15 and then 2 years later. We found that greater levels of emotional neglect were associated with blunted development of reward-related VS activity between the first and second assessments (as indexed by lower residualized change scores). Additionally, we found that decreases in this reward-related VS activity were related to greater depressive symptomatology and partially mediated the association between emotional neglect and subsequent depressive symptomatology. Our results provide an important demonstration that blunted development of reward-related VS activity as a function of emotional neglect predicts the emergence of depressive symptoms in adolescents. Further, our results are consistent with emerging evidence for the importance of reward-related VS dysfunction in the etiology and pathophysiology of depression. These results are a first step toward developing the ability to predict, prevent, and treat stress-related psychopathology through the targeting of specific neural phenotypes.


Independent calculation of monitor units for VMAT and SPORT.
Dose and monitor units (MUs) represent two important facets of a radiation therapy treatment. In current practice, verification of a treatment plan is commonly done in dose domain, in which a phantom measurement or forward dose calculation is performed to examine the dosimetric accuracy and the MU settings of a given treatment plan. While it is desirable to verify directly the MU settings, a computational framework for obtaining the MU values from a known dose distribution has yet to be developed. This work presents a strategy to calculate independently the MUs from a given dose distribution of volumetric modulated arc therapy (VMAT) and station parameter optimized radiation therapy (SPORT). The dose at a point can be expressed as a sum of contributions from all the station points (or control points). This relationship forms the basis of the proposed MU verification technique. To proceed, the authors first obtain the matrix elements which characterize the dosimetric contribution of the involved station points by computing the doses at a series of voxels, typically on the prescription surface of the VMAT/SPORT treatment plan, with unit MU setting for all the station points. An in-house Monte Carlo (MC) software is used for the dose matrix calculation. The MUs of the station points are then derived by minimizing the least-squares difference between doses computed by the treatment planning system (TPS) and that of the MC for the selected set of voxels on the prescription surface. The technique is applied to 16 clinical cases with a variety of energies, disease sites, and TPS dose calculation algorithms. For all plans except the lung cases with large tissue density inhomogeneity, the independently computed MUs agree with that of TPS to within 2.7% for all the station points. In the dose domain, no significant difference between the MC and Eclipse Anisotropic Analytical Algorithm (AAA) dose distribution is found in terms of isodose contours, dose profiles, gamma index, and dose volume histogram (DVH) for these cases. For the lung cases, the MC-calculated MUs differ significantly from that of the treatment plan computed using AAA. However, the discrepancies are reduced to within 3% when the TPS dose calculation algorithm is switched to a transport equation-based technique (Acuros™). Comparison in the dose domain between the MC and Eclipse AAA/Acuros calculation yields conclusion consistent with the MU calculation. A computational framework relating the MU and dose domains has been established. The framework does not only enable them to verify the MU values of the involved station points of a VMAT plan directly in the MU domain but also provide a much needed mechanism to adaptively modify the MU values of the station points in accordance to a specific change in the dose domain.


The comparison of del nido cardioplegia and crystalloid-based blood cardioplegia in adult isolated coronary bypass surgery: A randomized controlled trial.
In our study, patients who underwent isolated coronary artery bypass surgery (CABG) using Del Nido cardioplegia (DNC) and crystalloid-based cold blood cardioplegia (CBC) were compared. In this study, two groups of patients who underwent isolated CABG using DNC (n = 106) and CBC (n = 107) were prospectively randomized. Groups were compared in terms of many results such as troponin T, returning spontaneous rhythm, and cardioplegia volume. Median troponin T levels of the DNC and CBC groups were compared for the 0th hour (baseline), 12th, 36th, and 60th hours. There was no statistical difference between groups in troponin T levels of the baseline 0th hour (18[33] vs. 22[27] pg/ml; P = 0.724). Troponin T levels at the 12th hour were less in the DNC group than the CBC group but no statistical difference between the groups (790[735] vs. 826[820] pg/ml; P = 0.068), respectively. Troponin T levels at 36th and 60th hours were higher in the CBC group compared to the DNC group, and a statistical difference was observed (580[546] vs. 650[550] pg/ml; P = 0.030) and (359[395] vs. 421[400] pg/ml; P = 0.020), respectively. After X-clamping, the spontaneous rhythm rate was statistically higher in the DNC group than the CBC group (72.60% vs. 37.40%; P < 0.001). There was no statistical difference between the groups in terms of postoperative arrhythmia, hospital stay, and mortality rates (P > 0.05). Based on data we acquired from the study, we think that DNC is at least as safe and effective as CBC in adult CABG cases.


Contemporary role of prostate cancer antigen 3 in the management of prostate cancer.
Newly discovered biomarkers ideally should prove clinical usefulness, provide additional detection, staging, and prognosis information to improve individual risk assessment, and potentially permit targeted cancer therapy. To review, display, and evaluate the current evidence regarding the biologic and analytic approach of urinary prostate cancer gene 3 (PCA3) in prostate cancer (PCa) detection, staging, and prognosis, and its therapeutic potential. A systematic and comprehensive Medline search was performed using the Medical Subject Headings search terms PCA3, DD3, UPM3, prostate cancer, cell-lines, prostate tissue, prostate biopsy, detection, diagnosis, radical prostatectomy, staging, grading, progression, and gene therapy. Results were restricted to English-language papers published within the period 1999-2011. The PCA3 gene is highly overexpressed in specific PCa cell lines and prostatic tumours. In 2006, a simple and robust urine test (Progensa) became commercially available. Despite its costs, prostate cancer antigen 3 (PCA3) is superior to prostate-specific antigen (PSA) and percent free PSA in the early detection of PCa. PCA3 improves the diagnostic accuracy of externally validated nomograms among men with an elevated PSA undergoing biopsy. PCA3 independently predicts low-volume disease and pathologically insignificant PCa but is not associated with locally advanced disease and is limited in the prediction of aggressive cancer. Preliminary data demonstrate that combining PCA3 with other new biomarkers further improves diagnostic and prognostic accuracy. Finally, findings of the first PCA3-Gene-ViroTherapy study suggest therapeutic potential by exploiting PCA3 overexpression. PCA3, integrated in novel biopsy nomograms or risk stratification tools, can be used to counsel or confirm biopsy indications. If confirmed in further studies, using PCA3 together with established staging risk factors could assist clinicians in specific pretreatment decision making. So far no evidence for the usefulness of PCA3 in active surveillance programs has been presented.


Recent advances in anticancer drugs.
During the last few years, research in anticancer drug development has revealed a number of new approaches. These include new types of prodrugs, small peptides and synthetic molecules affecting signal transduction pathways and cell cycle, topoisomerase inhibitors, antisense compounds, anti-angiogenic and antimetastatic agents, gene therapy and vaccines. The aim of the meeting was to present and discuss the recent results in these areas, with respect to the R and D of new anticancer compounds. This review focuses on the most recent advances in anticancer drugs presented and discussed in the plenary sessions.


Cryptococcus neoformans: pseudohyphal forms surviving culture with Acanthamoeba polyphaga.
During experiments on the gastrointestinal tract as a possible portal of entry for Cryptococcus neoformans, we occasionally observed the free-living amoeba, Acanthamoeba polyphaga, growing in the presence of C. neoformans cultured from mouse feces. Examination of the amoebic trophozoites revealed that they were engorged with yeast cells. Over a period of 2 to 3 weeks of incubation, the amoebae apparently killed most of the yeast cells. Some of the surviving C. neoformans cells formed atypical colonies which contained pseudohyphae. Seven other strains have since been cultured with this amoeba. Pseudohyphal forms were found among the surviving colonies in all strains tested. Virulence studies were performed on one randomly selected pseudohyphal isolate from each of the eight strains of C. neoformans. Pseudohyphal isolates from seven of the eight strains failed to kill mice 30 days after intracranial inoculation. The potential role of soil amoebae in the control of C. neoformans in nature is discussed.


Effect of Inlet Air Temperature and Quinoa Starch/Gum Arabic Ratio on Nanoencapsulation of Bioactive Compounds from Andean Potato Cultivars by Spray-Drying.
Nanoencapsulation of native potato bioactive compounds by spray-drying improves their stability and bioavailability. The joint effect of the inlet temperature and the ratio of the encapsulant (quinoa starch/gum arabic) on the properties of the nanocapsules is unknown. The purpose of this study was to determine the best conditions for the nanoencapsulation of these compounds. The effects of two inlet temperatures (96 and 116 °C) and two ratios of the encapsulant (15 and 25% w/v) were evaluated using a factorial design during the spray-drying of native potato phenolic extracts. During the study, measurements of phenolic compounds, flavonoids, anthocyanins, antioxidant capacity, and various physical and structural properties were carried out. Higher inlet temperatures increased bioactive compounds and antioxidant capacity. However, a higher concentration of the encapsulant caused the dilution of polyphenols and anthocyanins. Instrumental analyses confirmed the effective encapsulation of the nuclei in the wall materials. Both factors, inlet temperature, and the encapsulant ratio, reduced the nanocapsules' humidity and water activity. Finally, the ideal conditions for the nanoencapsulation of native potato bioactive compounds were determined to be an inlet temperature of 116 °C and an encapsulant ratio of 15% w/v. The nanocapsules obtained show potential for application in the food industry.


Different Abnormalities of Cortical Neural Synchronization Mechanisms in Patients with Mild Cognitive Impairment due to Alzheimer's and Chronic Kidney Diseases: An EEG Study.
This study tested whether resting state alpha rhythms (8-13 Hz) may characterize mild cognitive impairment due to Alzheimer's disease (ADMCI) compared with MCI due to chronic kidney disease (CKDMCI). Clinical and resting state eyes-closed electroencephalographic (rsEEG) rhythms from 40 ADMCI, 29 CKDMCI, and 45 cognitively normal elderly (Nold) subjects were available in a national archive. Age, gender, and education were matched in the three groups, and Mini-Mental State Evaluation (MMSE) score was paired in the ADMCI and CKDMCI groups. Delta (<4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz), and gamma (30-40 Hz) cortical sources were estimated by eLORETA freeware and classified across individuals by area under the receiver operating characteristic curve (AUROCC). Compared with Nold group, posterior alpha 1 source activities were more reduced in ADMCI than CKDMCI group. In contrast, widespread delta source activities were greater in CKDMCI than ADMCI group. These source activities correlated with the MMSE score and correctly classified between Nold and all MCI individuals (AUROCC = 0.8-0.85) and between ADMCI and CKDMCI subjects (AUROCC = 0.75). These results suggest that early AD affects cortical neural synchronization at alpha frequencies underpinning brain arousal and low vigilance in the quiet wakefulness. In contrast, CKD may principally affect cortical neural synchronization at the delta frequencies. Future prospective cross-validation studies will have to test these candidate rsEEG markers for clinical applications and drug discovery.


Oral rehabilitation with implant-retained prostheses following ablative surgery and reconstruction with free flaps.
Ablative surgery of the oral tissues may result in significant facial deformity, poor oral function, and psychologic detriment. Immediate surgical reconstruction with vascularized free flaps has become increasingly popular, but the oral rehabilitation of these patients with conventional dental prostheses is usually unsuccessful. The results and clinical experiences of treating a group of 17 patients with ablative surgery, immediate reconstruction with free flaps, and restoration with mandibular implant-retained prostheses are presented after follow-up periods of 6 months to 7 years. Most patients expressed a high degree of satisfaction with their prostheses. General principles and guidelines for the provision of this effective treatment modality are discussed.


Adenovirus F protein as a delivery vehicle for botulinum B.
Immunization with recombinant carboxyl-terminal domain of the heavy chain (Hc domain) of botulinum neurotoxin (BoNT) stimulates protective immunity against native BoNT challenge. Most studies developing a botulism vaccine have focused on the whole Hc; however, since the principal protective epitopes are located within beta-trefoil domain (Hcbetatre), we hypothesize that immunization with the Hcbetatre domain is sufficient to confer protective immunity. In addition, enhancing its uptake subsequent to nasal delivery prompted development of an alternative vaccine strategy, and we hypothesize that the addition of targeting moiety adenovirus 2 fiber protein (Ad2F) may enhance such uptake during vaccination. The Hcbetatre serotype B immunogen was genetically fused to Ad2F (Hcbetatre/B-Ad2F), and its immunogenicity was tested in mice. In combination with the mucosal adjuvant, cholera toxin (CT), enhanced mucosal IgA and serum IgG Ab titers were induced by nasal Hcbetatre-Ad2F relative to Hcbetatre alone; however, similar Ab titers were obtained upon intramuscular immunization. These BoNT/B-specific Abs induced by nasal immunization were generally supported in large part by Th2 cells, as opposed to Hcbetatre-immunized mice that showed more mixed Th1 and Th2 cells. Using a mouse neutralization assay, sera from animals immunized with Hcbetatre and Hcbetatre-Ad2F protected mice against 2.0 LD50. These results demonstrate that Hcbetatre-based immunogens are highly immunogenic, especially when genetically fused to Ad2F, and Ad2F can be exploited as a vaccine delivery platform to the mucosa.


First-line therapy in ovarian cancer trials.
At the 4th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup (GCIG) held in Vancouver, Canada, in June 2010, representatives of 23 cooperative research groups studying gynecologic cancers gathered to establish international consensus on issues critical to the conduct of large randomized trials. The process focused on 13 predetermined questions. Group A, 1 of the 3 discussion groups, addressed the first 5 questions, examining first-line therapies in newly diagnosed ovarian cancer patients. A1: What are the appropriate end points for different trials (maintenance, upfront chemotherapy trials including molecular drugs)? A2: Are there any subgroups defined by tumor biology who need specific treatment options/trials? A3: Is the 2004 GCIG-recommended standard comparator arm still valid? A4: What is the role of modifying dose, schedule, and delivery of chemotherapy? A5: What role does surgery play today?


Hypereosinophilic Syndrome: Hacettepe Experience.
The aim was to evaluate baseline demographic, clinical, and laboratory characteristics, treatment modalities, and outcome of children with idiopathic hypereosinophilic syndrome (HES) followed up in our center. Children who fulfilled the criteria of idiopathic HES followed up at Hacettepe University Faculty of Medicine, Pediatric Hematology Department between June 2004 and October 2013 were included in this study. Medical records of all children with idiopathic HES were reviewed to obtain regarding data. The mean age of 6 children with idiopathic HES was 52.8±44.3 months (13 to 132 mo) at diagnosis. Among 6 children with idiopathic HES; 2 had pulmonary involvement; 1 had cardiac and pulmonary involvement and splenomegaly; 1 had cardiac involvement and hepatosplenomegaly; 1 had cardiac and central nervous system involvement; and 1 had skin involvement. The mean follow-up duration was 36.5±31.4 months. Methyl prednisolone (MP) was used for the first-line therapy. Complete response was achieved with MP in 3 children. All steroid responsive children are alive; whereas 3 children who did not respond to MP had expired. In conclusion, cardiac and pulmonary involvement is the major causes of mortality in HES. Resistance to steroid therapy indicates poor prognosis.


Primary parotid adenocarcinoma metastasis to the spleen with PIK3CA mutation: cytological findings and review of the literature.
Primary solid tumor metastasis to the spleen is a rare event, and often presents as an incidental finding without clinical symptoms of the patient. The most common primary tumors that metastasize to the spleen are colorectal, ovarian, and lung carcinomas. Parotid tumor metastasis to the spleen is extremely rare. We report an unusual case of metastatic parotid adenocarcinoma NOS (not otherwise specified) to the spleen. The patient presented with primary parotid carcinoma and underwent left parotidectomy. On pathological examination of the primary parotid tumor, no vascular or perineural invasion was found; all surgical resection margins and neck lymph nodes were also uninvolved by the tumor. No other therapy was given after the surgery. Four years later, the patient developed a solitary splenic lesion detected by a routine follow-up computed tomography (CT) scan. The subsequent fine needle aspiration (FNA) and splenectomy showed a metastatic adenocarcinoma consistent with the parotid primary. Immunohistochemical (IHC) staining of the metastatic tumor also showed a similar pattern as that of the primary tumor, including positivity for pancytokeratin, S-100 and SOX10, supporting the diagnosis. Furthermore, A PIK3CA (phosphatidylinositol 3-kinase catalytic subunit) mutation was also detected in the splenic metastasis. Based on our review of the literature, we believe that this is the first report of such a case. Accurate diagnosis and molecular characterization of the splenic metastasis have a critical impact on the clinical management of the patient.


Intrauterine fetal death with subsequent quill exfoliation and dissemination in a North American porcupine (Erethizon dorsatum).
An adult female, wild North American porcupine (Erethizon dorsatum) presented with bilateral cataracts and naso-ocular discharge. A pregnancy was identified by radiography with a near-full-term fetus, which was delivered stillborn 4 wk later with hard, developed quills. At that time, a repeated examination and further imaging, including computed tomography, demonstrated a uterine mass that was identified as a choriocarcinoma following ovariohysterectomy. Additionally, numerous exfoliated quills were discovered throughout the abdomen, most of which were removed during the surgical procedure. Ultimately, development of peritonitis despite medical care led to the porcupine's death. Necropsy confirmed a wide migration of the quills with extensive serosal adhesions and granulomas affecting liver, lungs, urinary bladder, kidneys, and gastrointestinal tract.


Intraneural perineurioma: a retrospective study of 19 patients.
Intraneural perineurioma is a benign neoplasm of peripheral nerve sheath with perineurial cell origin that typically affects teenagers and young adults and tends to result in a motor-predominant neuropathy. The aim of our study is to present the epidemiology, clinical presentation, way of diagnosis and management plan in a consecutive patient series. Ninteen patients diagnosed as having intraneural perineurioma were retrospectively chart reviewed. Diagnosis was done by MRI and/or biopsy with morphological, immunohistochemical staining study confirmation. Patients assessments included gender, age, symptoms, tumor localization, radiological aspect, management and pathological confirmation.Sex ratio was 10 males to 9 females with mean age of 31.2 (15-64). All the patients presented with motor deficit, ten with sensory deficit. Upper limb was involved in 11 cases (among them 4 lesions of brachial plexus), the lower limb in 8 cases. On magnetic resonance imaging, 16 patients showed a nerve enlargement whereas 5 presented with atypical fusiform tumor. Eighteen patients were operated for excision biopsy and/or palliative treatment for their motor deficit. Anatomopathological analysis confirmed the diagnosis in seventeen cases with a morphological pseudo-onion bulb shape and/or specific immunohistochemical assay. One patient had only palliative treatment without excision biopsy. Our data confirmed the equal penetration of intraneural perineurioma to both sex and affected limb. Because of the benignity of the tumor, the surgical treatment focused on optimizing the functional outcome. A prospective study with long term follow-up is required for this under-diagnosed tumor.


Automated image-based analysis unveils acute effects due to sub-lethal pesticide doses exposure.
Pesticides are still abused in modern agriculture. The effects of their exposure to even sub-lethal doses can be detrimental to ecosystem stability and human health. This work aims to validate the use of machine learning techniques for recognizing motor abnormalities and to assess any effect post-exposure to a minimal dosage of these substances on a model organism, gaining insights into potential risks for human health. The test subject was the Mediterranean fruit fly, Ceratitis capitata (Wiedemann) (Diptera: Tephritidae), exposed to food contaminated with the LC30 of Carlina acaulis essential oil. A deep learning approach enabled the pose estimation within an arena. Statistical analysis highlighted the most significant features between treated and untreated groups. Based on this analysis, two learning-based algorithms, Random Forest (RF) and XGBoost were employed. The results were compared through different metrics. RF algorithm generated a model capable of distinguishing treated subjects with an area under the receiver operating characteristic curve of 0.75 and an accuracy of 0.71. Through an image-based analysis, this study revealed acute effects due to minimal pesticide doses. So, even small amounts of these biocides drifted far from distribution areas may negatively affect the environment and humans.


Leeches run cold, then hot.
Food processing is costly, potentially limiting the energy and time devoted to other essential functions such as locomotion or reproduction. In ectotherms, post-prandial thermophily, the selection of a warm environmental temperature after feeding, may be advantageous in minimizing the duration of this elevated cost. Although present in many vertebrate taxa, this behaviour had not previously been observed in invertebrates. Sanguivorous leeches ingest large blood meals that are costly to process and limit mobility until excess fluid can actively be expelled to reduce body volume. When presented with a temperature gradient from 10°C to 30°C, leeches select a temperature that is significantly warmer (24.3 ± 0.9°C, n = 6) than their acclimation temperature (T(a), 21°C). Unfed leeches preferred temperatures that were significantly cooler than ambient (12.8 ± 0.9°C, n = 6). This behavioural strategy is consistent with minimizing the time course of elevated post-feeding energy costs and reducing energy expenditure during fasting. Our observations raise the possibility that thermoregulatory behaviour of this type is an unrecognized feature of other invertebrate taxa.


Functional brain connectivity at rest changes after working memory training.
Networks of functional connectivity are highly consistent across participants, suggesting that functional connectivity is for a large part predetermined. However, several studies have shown that functional connectivity may change depending on instructions or previous experience. In the present study, we investigated whether 6 weeks of practice with a working memory task changes functional connectivity during a resting period preceding the task. We focused on two task-relevant networks, the frontoparietal network and the default network, using seed regions in the right middle frontal gyrus (MFG) and the medial prefrontal cortex (PFC), respectively. After practice, young adults showed increased functional connectivity between the right MFG and other regions of the frontoparietal network, including bilateral superior frontal gyrus, paracingulate gyrus, and anterior cingulate cortex. In addition, they showed reduced functional connectivity between the medial PFC and right posterior middle temporal gyrus. Moreover, a regression with performance changes revealed a positive relation between performance increases and changes of frontoparietal connectivity, and a negative relation between performance increases and changes of default network connectivity. Next, to study whether experience-dependent effects would be different during development, we also examined practice effects in a pilot sample of 12-year-old children. No practice effects were found in this group, suggesting that practice-related changes of functional connectivity are age-dependent. Nevertheless, future studies with larger samples are necessary to confirm this hypothesis.


ATP is required for initiation of poliovirus RNA synthesis in vitro: demonstration of tyrosine-phosphate linkage between in vitro-synthesized RNA and genome-linked protein.
Poliovirus replicase- and host factor-catalyzed copying of 3'-terminal polyadenylic acid [poly(A)] of poliovirion RNA was studied. Host factor-stimulated synthesis of polyuridylic acid [poly(U)] by the replicase required ATP in addition to UTP. ATP was not required for the oligouridylic acid-primed copying of 3'-terminal poly(A) of virion RNA. GTP, CTP, and AMP-PCP (5'-adenylyl beta-gamma methylenediphosphate, an ATP analog) could not replace ATP in host factor-stimulated synthesis of poly(U). Antibodies to poliovirus genome-linked protein (VPg) specifically precipitated in vitro-synthesized poly(U) from a host factor-stimulated reaction. The poly(U) synthesized in a host factor-stimulated reaction was shown to be attached to VPg precursor polypeptide(s) via a tyrosine-phosphate bond as found in poliovirion VPg-RNA.


Multiple antibiotic resistance of heterotrophic bacteria isolated from Siberian lakes subjected to differing degrees of anthropogenic impact.
The antibiotic resistance profiles of 150 heterotrophic bacterial isolates recovered from two lakes in Southern Siberia was determined to examine the effect of anthropogenic disturbance on aquatic ecosystems. Resistance was detected in at least one strain for seven of the eight antibiotics tested, the exception being amikacin. Resistance to antibiotics predominated in the areas of the lakes likely to be under highest anthropogenic disturbance. Resistance was more frequently observed among isolates recovered from within the proximity to a tourist resort (Lake Shira; 63% of bacteria with multiple antibiotic resistance (MAR) in the resort part), or the shore line (Lake Shunet; 100% of bacteria with MAR) than among isolates from the center of each lake; 42.5% of bacteria with MAR from Lake Shira and 25%/75% of bacteria are resistant to three/four antibiotics consequently from Lake Shunet. Plasmid profiles were determined from a sample of 37 multiply resistant bacteria, and between one and four plasmids were isolated from each isolate; the plasmids ranged in size from 2.3 to 23.1 kb. These observations are consistent with anthropogenic disturbance playing one of the key roles in the dissemination of antibiotic resistance in the aquatic ecosystems.


Hsp90 Inhibitors in Parasitic Nematodes: Prospects and Challenges.
Hsp90 inhibitors are well characterized in relation to their effects in a variety of tumors, with several inhibitors in various phases of clinical development. In recent years, the same inhibitor classes have been tested for efficacy in other systems, such as Alzheimer's disease and a variety of infectious disease models, including fungal and parasitic targets. In this article we discuss the repurposing of Hsp90 inhibitors for parasitic disease with a focus on parasitic nematode infections. We summarize the data that indicate that Hsp90 is functionally diverse in different nematode species and we discuss the challenges and prospects for developing these inhibitors as next generation chemotherapeutic tools.


Cold Vapor Generation beyond the Input Solar Energy Limit.
100% efficiency is the ultimate goal for all energy harvesting and conversion applications. However, no energy conversion process is reported to reach this ideal limit before. Here, an example with near perfect energy conversion efficiency in the process of solar vapor generation below room temperature is reported. Remarkably, when the operational temperature of the system is below that of the surroundings (i.e., under low density solar illumination), the total vapor generation rate is higher than the upper limit that can be produced by the input solar energy because of extra energy taken from the warmer environment. Experimental results are provided to validate this intriguing strategy under 1 sun illumination. The best measured rate is ≈2.20 kg m-2 h-1 under 1 sun illumination, well beyond its corresponding upper limit of 1.68 kg m-2 h-1 and is even faster than the one reported by other systems under 2 sun illumination.


Guaiphenesin-ketamine-xylazine infusion to maintain anesthesia in mules undergoing field castration.
In order to determine whether a combination of guaiphenesin, ketamine and xylazine can induce safe and satisfactory anaesthesia in mules undergoing field castration, eight healthy adult intact male mules were employed. They were premedicated with intravenous (IV) xylazine (1.3 mg/kg); an additional dose of xylazine (0.3 mg/kg IV) was administered in case of inadequate depth of sedation. Anaesthesia was induced with IV thiopental (6 mg/kg). The quality of sedation and induction was recorded. Anaesthesia was maintained with an infusion of guaiphenesin (50 mg/mL), ketamine (2 mg/mL) and xylazine (1 mg/mL) (GKX). The spermatic cord of each testis was infiltrated with 5 mL of 2% lidocaine. During anaesthesia heart rate (HR), respiratory rate (RR), rectal temperature (RT) and haemoglobin oxygen saturation (SpO2) were measured every 5 min. The data were analysed with simple one-way analysis of variance (ANOVA). A P value < 0.05 was considered statistically significant. Time of anesthesia, time of surgery and time of recovery were recorded. Only one mule required an additional dose of xylazine to achieve a satisfactory depth of sedation. Thiopental at the dose of 6 mg/kg IV resulted in smooth induction and lateral recumbency in all animals. GKX provided adequate anaesthesia to perform castration in all mules. Muscle relaxation was deemed adequate and physiological variables remained stable and within references values during the anaesthesia and did not change in response to surgical stimulation. Time (mean ± standard deviation) from the end of the infusion to sternal recumbency and time from sternal recumbency to standing were 27.7 ± 4.6 and 30.1 ± 7.7 min, respectively. The combination of xylazine, thiopental and GKX provides satisfactory short-term anaesthesia in mules undergoing field castration.


C3 and C4 pathways of photosynthetic carbon assimilation in marine diatoms are under genetic, not environmental, control.
Marine diatoms are responsible for up to 20% of global CO(2) fixation. Their photosynthetic efficiency is enhanced by concentrating CO(2) around Rubisco, diminishing photorespiration, but the mechanism is yet to be resolved. Diatoms have been regarded as C(3) photosynthesizers, but recent metabolic labeling and genome sequencing data suggest that they perform C(4) photosynthesis. We studied the pathways of photosynthetic carbon assimilation in two diatoms by short-term metabolic (14)C labeling. In Thalassiosira weissflogii, both C3 (glycerate-P and triose-P) and C4 (mainly malate) compounds were major initial (2-5 s) products, whereas Thalassiosira pseudonana produced mainly C3 and C6 (hexose-P) compounds. The data provide evidence of C(3)-C(4) intermediate photosynthesis in T. weissflogii, but exclusively C(3) photosynthesis in T. pseudonana. The labeling patterns were the same for cells grown at near-ambient (380 microL L(-1)) and low (100 microL L(-1)) CO(2) concentrations. The lack of environmental modulation of carbon assimilatory pathways was supported in T. pseudonana by measurements of gene transcript and protein abundances of C(4)-metabolic enzymes (phosphoenolpyruvate carboxylase and phosphoenolpyruvate carboxykinase) and Rubisco. This study suggests that the photosynthetic pathways of diatoms are diverse, and may involve combined CO(2)-concentrating mechanisms. Furthermore, it emphasizes the requirement for metabolic and functional genetic and enzymic analyses before accepting the presence of C(4)-metabolic enzymes as evidence for C(4) photosynthesis.


Privacy-Preserving Automatic Collection of Acoustic Voiding Events.
Uroflowmetry is a non-invasive diagnostic test used to evaluate the function of the urinary tract. Despite its benefits, it has two main limitations: high intra-subject variability of flow parameters and the requirement for patients to urinate on demand. To overcome these limitations, we have developed a low-cost ultrasonic platform that utilizes machine learning (ML) models to automatically detect and record natural in-home voiding events, without any need for user intervention. This platform operates outside of human-audible frequencies, providing privacy-preserving, automatic uroflowmetries that can be conducted at home as part of daily routines. After evaluating several machine learning algorithms, we found that the Multi-layer Perceptron classifier performed exceptionally well, with a classification accuracy of 97.8% and a low false negative rate of 1.2%. Furthermore, even on lightweight SVM models, performance remains robust. Our results also showed that the voiding flow envelope, helpful for diagnosing underlying pathologies, remains intact even when using only inaudible frequencies.Clinical relevance- This classification task has the potential to be part of an essential toolkit for urology telemedicine. It is especially useful in areas that lack proper medical infrastructure but still host ubiquitous embedded privacy-preserving audio capture devices with Edge AI capabilities.


Analysis on chronic pain management: Focus on the Italian network.
The Italian Law 38/2010, 'Dispositions to guarantee access to Palliative Care and Pain Management' orders that the health care systems of Italian regions create dedicated structures for palliative care and pain therapies, according to a specific organizational model called 'Hub-Spoke', to ensure the diagnostic-therapeutic continuity of patients affected by chronic pain (CP). The aim of our study was to investigate the Italian pain therapy network, 8 years following the approval of the Law. We sent a questionnaire to the national health representatives operating in CP management. The main result emerging from the analysis concerns the management of mini-invasive procedures, showing that 93.2% of the responding facilities carry out invasive procedures, 6.8% do not perform them and that 100% of the facilities belonging to 12 regions provided these procedures, while in eight regions more than 80%. Finally, only 38.5% of facilities declared to have a shared protocol with the relevant territorial facilities in order to guarantee the process of care and assistance of patients affected by CP. In conclusion, our study demonstrated the efficacy of the organizational model in most of the responding facilities, although the territorial management of patients after their hospital discharge should be strengthened.


Comparison of In Vitro Assays in Selecting Radiotracers for In Vivo P-Glycoprotein PET Imaging.
Positron emission tomography (PET) imaging of P-glycoprotein (P-gp) in the blood-brain barrier can be important in neurological diseases where P-gp is affected, such as Alzheimer´s disease. Radiotracers used in the imaging studies are present at very small, nanomolar, concentration, whereas in vitro assays where these tracers are characterized, are usually performed at micromolar concentration, causing often discrepant in vivo and in vitro data. We had in vivo rodent PET data of [11C]verapamil, (R)-N-[18F]fluoroethylverapamil, (R)-O-[18F]fluoroethyl-norverapamil, [18F]MC225 and [18F]MC224 and we included also two new molecules [18F]MC198 and [18F]KE64 in this study. To improve the predictive value of in vitro assays, we labeled all the tracers with tritium and performed bidirectional substrate transport assay in MDCKII-MDR1 cells at three different concentrations (0.01, 1 and 50 µM) and also inhibition assay with P-gp inhibitors. As a comparison, we used non-radioactive molecules in transport assay in Caco-2 cells at a concentration of 10 µM and in calcein-AM inhibition assay in MDCKII-MDR1 cells. All the P-gp substrates were transported dose-dependently. At the highest concentration (50 µM), P-gp was saturated in a similar way as after treatment with P-gp inhibitors. Best in vivo correlation was obtained with the bidirectional transport assay at a concentration of 0.01 µM. One micromolar concentration in a transport assay or calcein-AM assay alone is not sufficient for correct in vivo prediction of substrate P-gp PET ligands.


Iron absorption in normal subjects and patients with idiopathic haemochromatosis: relationship with serum ferritin concentration.
In 52 normal subjects there was an inverse relationship between serum ferritin concentration and iron absorption. In 21 measurements in 15 patients with idiopathic haemochromatosis there was a similar inverse relationship but absorption was higher in relation to iron stores at all levels. Haemochromatotic patients with normal serum ferritin levels had abnormally high values for desferrioxamine chelatable iron and there was no correlation between chelatable iron and iron absorption.


Fenfluramine and phentermine and cardiovascular findings: effect of treatment duration on prevalence of valve abnormalities.
The combination of fenfluramine and phentermine was a widely used obesity treatment before the withdrawal of fenfluramine for an association with heart valve regurgitation. The prevalence and clinical significance of regurgitation among patients treated with these medications has yet to be fully established. To evaluate the potential association between the duration of treatment and the prevalence of heart valve abnormalities, we examined 1163 patients who had taken fenfluramine-phentermine and 672 control patients who had not taken the drug combination within 5 years. Mild or greater aortic regurgitation was present in 8.8% of treated patients and 3.6% of control patients (P<0.001). Moderate or greater mitral regurgitation was present in 2.6% of treated patients and 1.5% of control patients (P=0.18). The adjusted odds ratio compared with controls of aortic regurgitation of mild or greater severity increased according to duration of treatment: 90 to 180 days, 1.5 (P=0.23); 181 to 360 days, 2.4 (P=0.002); 361 to 720 days, 4.6 (P<0.001); >720 days, 6.2 (P<0.001). This is the largest study to demonstrate a relation between the length of treatment with fenfluramine-phentermine and the prevalence of valvular abnormalities. These findings suggest that valvular abnormalities in patients who took fenfluramine-phentermine primarily involve those who had taken these medications for >6 months and predominantly results in mild aortic regurgitation. The valve regurgitation identified by this study was not accompanied by significant differences in cardiovascular symptoms nor physical findings other than a higher prevalence of heart murmurs.


Investment policies and procedures of the social security trust funds.
In this article, the Deputy Commissioner of Social Security for Programs describes the policies and procedures that have been followed in investing the assets of the Social Security trust funds, explores possible alternative investment areas, and counters criticisms of investment results and maturity durations. The author's analysis shows that a departure from the current practice of investing most of the assets in long-term special issues of Federal debt would have adverse consequences for the private industrial economy, the Treasury Department, or the economy in general. He notes that, although the interest income of the trust funds in 1980 amounted to only 2.46 percent of the Social Security program's total income, the amount involved--$3.85 billion--was 1.5 times as large as total administrative expenses.


Differential diagnosis of type 2 neurofibromatosis: molecular discrimination of NF2 and sporadic vestibular schwannomas.
Patients who present with unilateral vestibular schwannomas either at a young age or with additional features of type 2 neurofibromatosis (NF2) are at risk of developing bilateral disease and transmitting a risk of neurogenic tumours to their offspring. We have identified 15 patients from a series of 537 with unilateral vestibular schwannomas who also had one or more of the following: other tumours (10/15), features of NF2 (3/15), or a family history of neurogenic tumours (5/15). No germline NF2 mutations were detected and in 7/9 cases where tumour material was available for analysis a germline mutation in the NF2 gene has been excluded. Although a possibility of gonosomal mosaicism still exists, exclusion tests for the offspring are now possible. We suggest a general strategy, based on analysis of tumour DNA, for distinguishing sporadic and familial cases of tumours caused by two hit mechanisms. Application of this strategy suggests that most instances of unilateral vestibular schwannoma which do not fulfil criteria for NF2 represent chance occurrences.


Mechanistic Insight into the Regulation of Lipoxygenase-Driven Lipid Peroxidation Events in Human Spermatozoa and Their Impact on Male Fertility.
A prevalent cause of sperm dysfunction in male infertility patients is the overproduction of reactive oxygen species, an attendant increase in lipid peroxidation and the production of cytotoxic reactive carbonyl species such as 4-hydroxynonenal. Our previous studies have implicated arachidonate 15-lipoxygenase (ALOX15) in the production of 4-hydroxynonenal in developing germ cells. Here, we have aimed to develop a further mechanistic understanding of the lipoxygenase-lipid peroxidation pathway in human spermatozoa. Through pharmacological inhibition studies, we identified a protective role for phospholipase enzymes in the liberation of peroxidised polyunsaturated fatty acids from the human sperm membrane. Our results also revealed that arachidonic acid, linoleic acid and docosahexanoic acid are key polyunsaturated fatty acid substrates for ALOX15. Upon examination of ALOX15 in the spermatozoa of infertile patients compared to their normozoospermic counterparts, we observed significantly elevated levels of ALOX15 protein abundance in the infertile population and an increase in 4-hydroxynonenal adducts. Collectively, these data confirm the involvement of ALOX15 in the oxidative stress cascade of human spermatozoa and support the notion that increased ALOX15 abundance in sperm cells may accentuate membrane lipid peroxidation and cellular dysfunction, ultimately contributing to male infertility.


Gross deletions involving IGHM, BTK, or Artemis: a model for genomic lesions mediated by transposable elements.
Most genetic disruptions underlying human disease are microlesions, whereas gross lesions are rare with gross deletions being most frequently found (6%). Similar observations have been made in primary immunodeficiency genes, such as BTK, but for unknown reasons the IGHM and DCLRE1C (Artemis) gene defects frequently represent gross deletions ( approximately 60%). We characterized the gross deletion breakpoints in IGHM-, BTK-, and Artemis-deficient patients. The IGHM deletion breakpoints did not show involvement of recombination signal sequences or immunoglobulin switch regions. Instead, five IGHM, eight BTK, and five unique Artemis breakpoints were located in or near sequences derived from transposable elements (TE). The breakpoints of four out of five disrupted Artemis alleles were located in highly homologous regions, similar to Ig subclass deficiencies and Vh deletion polymorphisms. Nevertheless, these observations suggest a role for TEs in mediating gross deletions. The identified gross deletion breakpoints were mostly located in TE subclasses that were specifically overrepresented in the involved gene as compared to the average in the human genome. This concerned both long (LINE1) and short (Alu, MIR) interspersed elements, as well as LTR retrotransposons (ERV). Furthermore, a high total TE content (>40%) was associated with an increased frequency of gross deletions. Both findings were further investigated and confirmed in a total set of 20 genes disrupted in human disease. Thus, to our knowledge for the first time, we provide evidence that a high TE content, irrespective of the type of element, results in the increased incidence of gross deletions as gene disruption underlying human disease.


Borrelia burgdorferi lacking DbpBA exhibits an early survival defect during experimental infection.
Several Borrelia burgdorferi genes induced under mammalian host conditions have been purported to be important in Lyme disease pathogenesis based on their binding to host structures. These genes include the dbpBA locus, whose products bind host decorin and glycosoaminoglycans. Recently, the dbpBA genes were reported to be involved in borrelial infectivity. Here we extended the previous observations by using culture and quantitative PCR to evaluate low- and high-dose murine infection by a Delta dbpBA::Gent(r) derivative of B. burgdorferi strain B31. The results indicate that the Delta dbpBA::Gent(r) mutant is attenuated in the ability to initially colonize and then persist in multiple tissues. The mutant exhibited a colonization defect as early as 3 days postinfection, before the development of an adaptive immune response, and after low-dose infection of SCID mice, which are deficient in adaptive immunity. These findings suggest that the inability to adhere to host decorin may promote clearance of B. burgdorferi, presumably via innate immune mechanisms. In a high-dose infection, the mutant disseminated to several tissues, particularly joint tissue, but it was generally cleared from these tissues by 3 weeks postinfection. Finally, following high-dose infection of SCID mice, the dbpBA mutant exhibited only a mild colonization defect, suggesting that the adaptive response is involved in the clearance of the mutant in immunocompetent mice. Taken together, these results suggest that the DbpBA proteins facilitate the colonization of multiple tissues by B. burgdorferi and are required for optimal resistance to both innate and adaptive immune mechanisms following needle inoculation.


Nosocomial and community acquired infections in Korle Bu Teaching Hospital, Accra.
Nosocomial or hospital acquired infection has been recognized as a serious public health problem in the last twenty years. In most hospitals in Africa-South of the Sahara, although the types of community acquired infections are known, neither the magnitude, nor the common types of nosocomial infections has been documented. This study was carried out to find the prevalence of hospital and community acquired infections in hospitals, and to estimate the overall prevalence of HAI and CAI in Korle Bu Teaching Hospital. A one-day prevalence survey of nosocomial and community acquired infection in a tertiary-care hospital in Accra was performed using the 1980 British national protocol and the result was analyzed using computerized gargets. Of the 907 patients on admission (on the day of the study), 61 (6.7%) had hospital-acquired infection and 287 (31.6%) had community acquired infection. The commonest hospital acquired infection was wound infection followed by skin and lower respiratory infections. Of the community infections, the most common cases were lower respiratory and skin infections. Fifty-three percent of all patients were on antimicrobial treatment. Patients on metronidazole were 212 (44%), ampicillin/amoxicillin 199 (41.6%), cloxacillin 163 (34%) and gentamicin 135 (28%). Approximately 20% of patients were on three or more drugs. This study has shown that the prevalence of community acquired infections in our hospital is much higher than that from nosocomial infections and that the British national survey protocol can be used in countries with limited resources.


Incidence and distribution of microfungi in a treated municipal water supply system in sub-tropical Australia.
Drinking water quality is usually determined by its pathogenic bacterial content. However, the potential of water-borne spores as a source of nosocomial fungal infection is increasingly being recognised. This study into the incidence of microfungal contaminants in a typical Australian municipal water supply was carried out over an 18 month period. Microfungal abundance was estimated by the membrane filtration method with filters incubated on malt extract agar at 25 degrees C for seven days. Colony forming units were recovered from all parts of the system and these were enumerated and identified to genus level. The most commonly recovered genera were Cladosporium, Penicillium, Aspergillus and Fusarium. Nonparametric multivariate statistical analyses of the data using MDS, PCA, BEST and bubble plots were carried out with PRIMER v6 software. Positive and significant correlations were found between filamentous fungi, yeasts and bacteria. This study has demonstrated that numerous microfungal genera, including those that contain species which are opportunistic human pathogens, populate a typical treated municipal water supply in sub-tropical Australia.


Bidirectional citation searching to completion: an exploration of literature searching methods.
Literature reviews underpin the majority of research projects in the health sciences, and yet relatively little analysis has been published as to the most appropriate method to identify relevant literature, outside of specialist information journals. The method of applying keyword search queries to bibliographic databases using Boolean logic dominates literature reviews due to its easy application to the major online databases. However, it is recognised increasingly as being problematic where the research question cannot be clearly defined or requires an element of exploration, due to its reliance on author's use of titling and keywords and is unable to identify topics other than those defined in the search query. This paper discusses the relative merits of a systematic citation searching approach as both an alternative and a concurrent method to keyword searching. A method of citation searching, both forwards and backwards, which is iterated to form a closed loop solution, is discussed. An illustrative example is presented of both methods, applying them to the topic of the UK National Institute for Health and Care Excellence (NICE) cost-effectiveness threshold. The case study finds the citation searching approach dominates the traditional keyword searching approach, finding 76 papers of relevance, including all 15 found by the alternative approach. Conceptually, and in the example presented, it is demonstrated that the proposed method can represent a dominant strategy to the more traditional approach in some situations, highlighting that, wherever possible, it is preferential to employ multiple methods of searching. However, it is clear that a better understanding is required as to how we can most efficiently search the ever-growing sea of literature.


Benefit assessment of salt reduction in patients with hypertension: systematic overview.
We assessed the benefits and harm of reduced salt intake in patients with essential hypertension focusing on patient-relevant outcomes and blood pressure. A systematic search of five electronic databases was performed to identify high-quality secondary literature based on randomized controlled trials (RCTs). An update primary literature search (RCTs) was performed for the time period up to 2010 that was not covered by secondary literature. Major outcomes were death, cardiovascular morbidity/mortality, hospital stays, terminal renal failure, quality of life, and adverse events. Change in blood pressure was defined as surrogate parameter. Four different systematic reviews and two RCTs met the inclusion criteria. Only one review reported limited data on patient-relevant outcomes. Over an intervention period of up to 12 months, mean SBP was reduced by 3.6-8.0 mmHg in all reviews. For the same intervention period, a statistically significant advantage with regard to mean DBP reduction ranging from 1.9 to 2.8 mmHg was found in three reviews. The fourth publication reported a nonsignificant reduction (DBP reduction of 4.7 mmHg). None of the RCTs identified in the primary literature search update reported data on patient-relevant outcomes. However, both RCTs found blood pressure improvements with salt reduction. A benefit from a salt-reduced diet in patients with high blood pressure is not proven with regard to patient-relevant outcomes based on systematic reviews and RCTs published up to 2010. The results indicate a blood pressure-lowering effect through reduced salt intake in hypertensive patients.


Peroxisomal membrane ascorbate peroxidase is sorted to a membranous network that resembles a subdomain of the endoplasmic reticulum.
The peroxisomal isoform of ascorbate peroxidase (APX) is a novel membrane isoform that functions in the regeneration of NAD(+) and protection against toxic reactive oxygen species. The intracellular localization and sorting of peroxisomal APX were examined both in vivo and in vitro. Epitope-tagged peroxisomal APX, which was expressed transiently in tobacco BY-2 cells, localized to a reticular/circular network that resembled endoplasmic reticulum (ER; 3,3'-dihexyloxacarbocyanine iodide-stained membranes) and to peroxisomes. The reticular network did not colocalize with other organelle marker proteins, including three ER reticuloplasmins. However, in vitro, peroxisomal APX inserted post-translationally into the ER but not into other purified organelle membranes (including peroxisomal membranes). Insertion into the ER depended on the presence of molecular chaperones and ATP. These results suggest that regions of the ER serve as a possible intermediate in the sorting pathway of peroxisomal APX. Insight into this hypothesis was obtained from in vivo experiments with brefeldin A (BFA), a toxin that blocks vesicle-mediated protein export from ER. A transiently expressed chloramphenicol acetyltransferase-peroxisomal APX (CAT-pAPX) fusion protein accumulated only in the reticular/circular network in BFA-treated cells; after subsequent removal of BFA from these cells, the CAT-pAPX was distributed to preexisting peroxisomes. Thus, plant peroxisomal APX, a representative enzymatic peroxisomal membrane protein, is sorted to peroxisomes through an indirect pathway involving a preperoxisomal compartment with characteristics of a distinct subdomain of the ER, possibly a peroxisomal ER subdomain.


Proposals for leflunomide use to avoid lung injury in patients with rheumatoid arthritis.
Among the 5,043 consecutive patients registered in the postmarketing surveillance for leflunomide, 61 were reported to have lung injury and 24 died from it. The adjusted multivariate logistic regression analysis of the risk factors showed that preexisting interstitial lung disease posed the greatest risk, as well as loading dose, smoking history, and low body weight of 40 kg or less with odds ratios of 8.17, 3.97, 3.12, and 2.91, respectively. In 12 patients, lung injury developed even 2 months after leflunomide withdrawal. When patients with (n=9) and without (n=13) fatal outcome were compared, eight out of the former, and six out of the latter had preexisting interstitial lung disease; the former showed severe hypoxemia, high serum C-reactive protein level, hypoalbuminemia, and continuous lymphocytopenia, and required mechanical ventilation. On the basis of these results and literature review, the committee proposes that leflunomide should only be recommended as a second-line drug, should not be administered to patients with preexisting interstitial lung disease, should also not be administered to patients with smoking history or those with low body weight, and should be administered without loading dose. Careful monitoring is necessary, and when lung injury develops, leflunomide elimination using colestyramine is mandatory.


Characterization of carbapenem-non-susceptible Escherichia coli isolates from a university hospital in Taiwan.
To investigate characteristics of nine carbapenem-non-susceptible (CP-NS) Escherichia coli isolates collected between 1999 and 2005 at a Taiwanese university hospital. Genetic relatedness was analysed by PFGE. beta-Lactamases were characterized by PCR and isoelectric focusing. Outer membrane proteins and transcripts were investigated by SDS-PAGE and northern blotting. Cloning experiments were performed to investigate the role of membrane permeability in carbapenem non-susceptibility. The nine CP-NS isolates were found to produce the CMY-2 AmpC enzyme (n = 8), the CTX-M-14-type extended-spectrum beta-lactamase (ESBL) (n = 1), the SHV-12 ESBL (n = 1) and the IMP-8-type metallo-beta-lactamase (n = 1) alone or in combination. All CP-NS isolates revealed a decrease in the transcription and protein expression of ompC, and susceptibility to carbapenems was restored in one isolate by introducing the cloned ompC gene. PFGE revealed genetic diversity among the nine isolates. All patients with the CP-NS isolates had been treated with carbapenems (six patients) and/or extended-spectrum cephalosporins (five patients) before isolation. Our study suggests that the decreased susceptibility to carbapenems in E. coli in the hospital might arise by the stepwise accumulations of multiple drug-resistance determinants in different clones.


Treatment patterns and short-term outcomes in ischemic stroke in pregnancy or postpartum period.
Stroke, which is a rare but devastating event during pregnancy, occurs in 34 of every 100,000 deliveries; obstetricians are often the first providers to be contacted by symptomatic patients. At least one-half of pregnancy-related strokes are likely to be of the ischemic stroke subtype. Most pregnant or newly postpartum women with ischemic stroke do not receive acute stroke reperfusion therapy, although this is the recommended treatment for adults. Little is known about these therapies in pregnant or postpartum women because pregnancy has been an exclusion criterion for all reperfusion trials. Until recently, pregnancy and obstetric delivery were specifically identified as warnings to intravenous alteplase tissue plasminogen activator in Federal Drug Administration labeling. The primary study objective was to compare the characteristics and outcomes of pregnant or postpartum vs nonpregnant women with ischemic stroke who received acute reperfusion therapy. Pregnant or postpartum (<6 weeks; n = 338) and nonpregnant (n = 24,303) women 18-44 years old with ischemic stroke from 1991 hospitals that participated in the American Heart Association's Get With the Guidelines-Stroke Registry from 2008-2013 were identified by medical history or International Classification of Diseases, Ninth Revision, codes. Acute stroke reperfusion therapy was defined as intravenous tissue plasminogen activator, catheter-based thrombolysis, or thrombectomy or any combination thereof. A sensitivity analysis was done on patients who received intravenous tissue plasminogen activator monotherapy only. Chi-square tests were used for categoric variables, and Wilcoxon Rank-Sum was used for continuous variables. Conditional logistic regression was used to assess the association of pregnancy with short-term outcomes. Baseline characteristics of the pregnant or postpartum vs nonpregnant women with ischemic stroke revealed a younger group who, despite greater stroke severity, were less likely to have a history of hypertension or to arrive via emergency medical services. There were similar rates of acute stroke reperfusion therapy in the pregnant or postpartum vs nonpregnant women (11.8% vs 10.5%; P = .42). Pregnant or postpartum women were less likely to receive intravenous tissue plasminogen activator monotherapy (4.4% vs 7.9%; P = .03), primarily because of pregnancy and recent surgery. There was a trend toward increased symptomatic intracranial hemorrhage in the pregnant or postpartum patients who were treated with tissue plasminogen activator, yet no cases of major systemic bleeding or in-hospital death occurred, and there were similar rates of discharge to home. Data on the timing of pregnancy, which were available in 145 of 338 cases, showed that 44.8% of pregnancy-related strokes were antepartum, that 2.8% occurred during delivery, and that 52.4% were during the postpartum period. Using data from the Get With the Guidelines-Stroke Registry to assemble the largest cohort of pregnant or postpartum ischemic stroke patients who had been treated with reperfusion therapy, we observed that pregnant or postpartum women had similarly favorable short-term outcomes and equal rates of total reperfusion therapy to nonpregnant women, despite lower rates of intravenous tissue plasminogen activator use. Future studies should identify the characteristics of pregnant and postpartum ischemic stroke patients who are most likely to safely benefit from reperfusion therapy.


[Polyuria as postoperative complication of frontal meningioma].
We report the case of a 56-year-old man with a frontal meningioma who underwent scheduled surgery under balanced general anesthesia without complications and was then transferred to the intensive care postoperative recovery unit for observation. On the day of admission he developed polyuria and a decrease in central venous pressure. Plasma sodium and osmolarity were in the normal ranges but urine analysis showed hyponatremia and hypo-osmolarity, suggesting cerebral salt wasting syndrome. Physiological saline solution was infused to maintain osmolarity and plasma concentrations of sodium within normal ranges. Diuresis peaked on the sixth day after surgery at 17,600 mL in 24 hours and decreased gradually to normal on the eleventh day after admission. Elevated plasma concentrations of atrial natriuretic peptides confirmed the diagnosis. Correct management is essential when neurosurgery patients develop altered plasma and urinary sodium concentrations and osmolarity. Differential diagnosis involves considering diabetes insipidus, inappropriate secretion of antidiuretic hormone and salt wasting syndrome. Transfer to an intensive care postoperative recovery unit and early treatment are important for lowering the risk of complications and death.


Cbl-b restrains priming of pathogenic Th17 cells via the inhibition of IL-6 production by macrophages.
E3 ubiquitin ligase Cbl-b is involved in the maintenance of a balance between immunity and tolerance. Mice lacking Cbl-b are highly susceptible to experimental autoimmune encephalomyelitis (EAE), a Th17-mediated autoimmune disease. However, how Cbl-b regulates Th17 cell responses remains unclear. In this study, utilizing adoptive transfer and cell type-specific Cblb knockout strains, we show that Cbl-b expression in macrophages, but not T cells or dendritic cells (DCs), restrains the generation of pathogenic Th17 cells and the development of EAE. Cbl-b inhibits IL-6 production by macrophages that is induced by signaling from CARD9-dependent C-type lectin receptor (CLR) pathways, which directs T cells to generate pathogenic Th17 cells. Therefore, our data unveil a previously unappreciated function for Cbl-b in the regulation of pathogenic Th17 responses.


Kinetic and Computational Analysis of CO Substitution in a Dinuclear Osmium Carbonyl Complex: Intersection between Dissociative and Dissociative-Interchange Mechanisms.
The mechanism for the CO substitution reaction involving the diosmium carbonyl sawhorse complex Os2(μ-O2CH)2(CO)6, which contains an Os-Os single bond, two axial CO ligands, and four equatorial CO ligands, was investigated experimentally and theoretically. Kinetic measurements show 13CO axial substitution proceeding by a dissociative reaction that is first-order in the complex and zero-order in 13CO but with an unexpectedly negative entropy of activation. The corresponding electronic structure calculations yield an enthalpy of activation for axial CO dissociation that is much larger than that determined by the kinetic experiments, but in agreement with the complex's stability with respect to CO loss. Additional calculations yield a dissociative interchange transition state whose free energy, enthalpy, and entropy of activation are in good agreement with those obtained from the kinetic measurements for the apparently dissociative substitution. These results point to an exchange reaction mechanism that is surprisingly close to the poorly understood transition from a dissociative mechanism with a CO-loss intermediate to a dissociative interchange mechanism with a transition state involving both the entering and the leaving COs. The key to explain these findings is provided by the vibrational analysis, which shows very low energy wagging motions for the axial COs. Thus, the incoming CO only displaces the outgoing CO when the complex has an outgoing CO near the wag's turning point. This dissociative interchange mechanism predicted by the calculation explains the unexpected combination of kinetics and stability characteristics. Kinetics reveals that the reaction is first-order in the Os dimer with a negative Eyring entropy, while a stability study shows that the Os dimer's decomposition rate is several orders of magnitude slower than CO exchange.


Chronic Thromboembolic Pulmonary Hypertension Mimicking Acute Pulmonary Embolism: A Case Report.
BACKGROUND Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare form of pulmonary hypertension which is often caused by recurrent emboli. The reported prevalence in Latvia is 15.7 cases per million inhabitants. Several risk factors predispose patients to develop chronic thromboembolic pulmonary hypertension, including the presence of chronic myeloproliferative diseases and splenectomy. CASE REPORT We present a case of a 68-year-old woman with a variant of chronic myeloproliferative disease, essential thrombocythemia, splenectomy, and chronic thromboembolic pulmonary hypertension, in whom chronic thromboembolic pulmonary hypertension was mimicking acute pulmonary embolism. On admission, the patient had progressive dyspnea, elevated right ventricular systolic pressure (RVSP) 60-70 mmHg, and elevated thrombocytes, C-reactive protein, BNP, and d-dimer levels. These results, as well as the results of thoracic computed tomography angiography with contrast, supported the diagnosis of acute pulmonary embolism. During the sequent follow-up visit after 3 months of effective anticoagulant therapy, the patient had elevated RVSP: 55-60 mmHg. Therefore, right heart catheterization was performed, in which it was found that mPAP was 37 mmHg with PCWP 5 mm Hg and PVR 8.9 Wood units, confirming the CTEPH diagnosis. CONCLUSIONS Patients who are at high risk of thrombosis need an increased level of monitoring to be properly evaluated. An easy solution to misdiagnosis of CTEPH with an acute pulmonary embolism could be taking scrupulous patient history, which can reveal multiple risk factors of CTEPH development. The subsequent assessment of risk factors can lead to a more appropriate consideration of CTEPH diagnosis vs acute pulmonary embolism.


Type IV collagen modulates angiogenesis and neovessel survival in the rat aorta model.
Type IV collagen is a major basement membrane component that has been implicated in the regulation of angiogenesis. The purpose of this study was to evaluate the effect of type IV collagen on the angiogenic response of native endothelial cells in three-dimensional vascular organ culture. Rings of rat aorta were cultured under serum-free conditions in gels of type I collagen with or without type IV collagen. In the absence of type IV collagen, aortic rings generated neovessels, which proliferated until day 9 and gradually regressed during the second and third weeks of culture. Type IV collagen promoted neovessel elongation and survival in a dose-dependent manner. Microvascular length increased by 43, 57, and 119% over control values in cultures treated with 3, 30, and 300 microg/ml type IV collagen, respectively. When used at high concentrations (300 microg/ml) type IV collagen stabilized the neovascular outgrowths and prevented vascular regression. Type IV collagen also promoted the formation of neovessels, but significant stimulatory effects were observed only at an intermediate concentration (30 microg/ml) and were no longer significant at the high concentration (300 microg/ml). The observation that type IV collagen has dose-dependent effects on vascular elongation, proliferation, and stabilization, supports the concept that the developing basement membrane of neovessels acts as a solid-phase regulator of angiogenesis, whose function varies depending on the concentration of its molecular components.


Exploring marine Lactobacillus and its protein for probiotic-based oral cancer therapy.
Cancer is a life-threatening malignancy and one of the leading global causes of human mortality. New approaches are required for cancer therapy due to the unique properties of cancer cells and the side effects of chemotherapy. Probiotics have gained significant attention in the prevention and treatment of various diseases, including cancer. Therefore, the current study aimed to investigate the anti-cancer effects of probiotics, such as marine Lactobacillus species and their proteins. Five marine Lactobacillus species were isolated and identified from the Tamil Nadu Mangrove Pichavaram (TLMP) forest and named TLMP1, TLMP2, TLMP3, TLMP4, and TLMP5. The Lactobacillus isolates, and their proteins were administered to male golden Syrian hamsters. Tumor formation was effectively controlled in hamsters treated with crude Lactobacillus, extending their lifespan. Additionally, Lactobacillus proteins demonstrated an inhibitory effect on tumor formation in the treated group compared to the control. Molecular docking analysis revealed that Lactobacillus proteins interacted significantly with the cAMP-dependent protein kinase catalytic subunit alpha. Amino acid residues LYS791, MET793, ARG841, ARG842, and LEU844 were involved in active site binding and played a crucial role in inhibiting cAMP-dependent protein kinase.


Hydrogen-rich saline attenuates spinal cord hemisection-induced testicular injury in rats.
To study how hydrogen-rich saline (HS) promotes the recovery of testicular biological function in a hemi-sectioned spinal cord injury (hSCI) rat model, a right hemisection was performed at the T11-T12 of the spinal cord in Wistar rats. Animals were divided into four groups: normal group; vehicle group: sham-operated rats administered saline; hSCI group: subjected to hSCI and administered saline; HRST group: subjected to hSCI and administered HS. Hind limb neurological function, testis index, testicular morphology, mean seminiferous tubular diameter (MSTD) and seminiferous epithelial thickness (MSET), the expression of heme oxygenase-1 (HO-1), mitofusin-2 (MFN-2), and high-mobility group box 1 (HMGB-1), cell ultrastructure, and apoptosis of spermatogenic cells were studied. The results indicated that hSCI significantly decreased the hind limb neurological function, testis index, MSTD, and MSET, and induced severe testicular morphological injury. The MFN-2 level was decreased, and HO-1 and HMGB-1 were overexpressed in testicular tissues. In addition, hSCI accelerated the apoptosis of spermatogenic cells and the ultrastructural damage of cells in the hypophysis and testis. After HS administration, all these parameters were considerably improved, and the characteristics of hSCI testes were similar to those of normal control testes. Taken together, HS administration can promote the recovery of testicular biological function by anti-oxidative, anti-inflammatory, and anti-apoptotic action. More importantly, HS can inhibit the hSCI-induced ultrastructural changes in gonadotrophs, ameliorate the abnormal regulation of the hypothalamic-pituitary-testis axis, and thereby promote the recovery of testicular injury. HS administration also inhibited the hSCI-induced ultrastructural changes in testicular spermatogenic cells, Sertoli cells and interstitial cells.


[Influence of post-fixation time on shear bond strength of brackets fixed with different materials].
The purpose of this study was to evaluate the shear bond strength of four bonding materials for brackets, 10 minutes and 24 hours after their fixation, as well as the kinds of fracture observed. The buccal surfaces of 32 premolars were etched for 30 seconds with 35% phosphoric acid, and brackets were bonded using Orthodontic Concise (3M) and Z100 (3M). In other 32 premolars, brackets were bonded with Fuji I (GC) and Fuji Ortho LC (GC) on the buccal surfaces, without acid etching. After the bonding procedures, 32 samples were stored in distilled water at 37 degrees C for 10 minutes, and 32 samples were stored at the same temperature for 24 hours. The samples were then submitted to shear bond strength testing in an Instron testing machine, at a crosshead speed of 0.5 mm/min. The results were submitted to ANOVA and Tukey's test (p < 0.05). The results indicated that, for 10 minutes and 24 hours, Orthodontic Concise showed shear bond strength values (6.22 and 7.73 MPa, respectively) higher than Fuji Ortho LC (3.32 and 5.10 MPa), Z100 (2.72 and 4.51 MPa) and Fuji I (2.52 and 4.54 MPa). No statistical difference was verified between Fuji Ortho LC, Z100 and Fuji I (p < 0.05). In conclusion, Orthodontic Concise showed better shear bond strength values than the other three bonding materials, for both 10-minute and 24-hour storage periods; the shear bond strength averages were higher for the storage time of 24 hours, for all tested materials, and a great number of adhesive fractures were observed in the specimens which received Fuji I, Orthodontic Concise and Z100.


Multivariate analysis of HLA loci in conjunction with a thyrotropin receptor codon 52 polymorphism in conferring risk of Graves' disease.
Recent reports have suggested that the HLA alleles DRB3*0101 or DQA1*0501 confer greater susceptibility to Graves' disease than does the DR3 allele. We have reported previously that a non-HLA-linked allele, a polymorphism in codon 52 of the human thyrotropin receptor gene, is highly associated with Graves' disease in females. To determine which of these four susceptibility alleles confers greater independent risk for the development of Graves' disease, we analyzed the alleles in 134 North American Caucasian females who have Graves' disease (n = 69) or are normal controls (n = 65) in a logistic regression model. While we found each of these alleles to be associated with Graves' disease when analyzed independently (corrected p < 0.01 for each of 4 alleles tested), only DR3 (p = 0.0001) and the thyrotropin receptor polymorphism (p = 0.0060) maintained a statistically significant independent association when assessed in conjunction with each of the other alleles in a logistic model. We conclude that DR3 confers the greatest susceptibility to Graves' disease (odds ratio = 7.6) of the alleles within the HLA locus, and that any association between DRB3*0101 or DQA1*0501 and Graves' disease may be a result of the tight linkage disequilibrium between these alleles and DR3. In addition, we found the non-HLA-linked thyrotropin receptor codon 52 polymorphism to confer significant independent risk of Graves' disease (odds ratio = 9.0). Further, because 6 of 6 individuals who possessed both DR3 and the thyrotropin receptor polymorphism had Graves' disease, while no individual in the normal control group possessed both alleles, study of a larger population to assess the potential synergism between these 2 alleles is warranted.


An outbreak of epidemic keratoconjunctivitis caused by adenovirus type 37.
An outbreak of acute keratoconjunctivitis in an ophthalmology department affected 15 patients and seven members of staff and necessitated temporary closure of the unit. Adenovirus (Ad) was isolated from eye swabs taken during the outbreak, but typing of the isolates by virus neutralisation assay proved unsatisfactory, wrongly assigning the isolate to serotype 10. A robust and rapid method for preparing microgram amounts of Ad DNA from infected cells was devised and used as the basis of a non-radioactive method for routine genotyping of adenovirus clinical isolates. All isolates associated with the outbreak, and one from a patient presenting at a nearby hospital during the outbreak, were found to have restriction endonuclease digestion patterns characteristic of Ad 37.


Nutrition and Swallowing Therapy in Head and Neck Cancer: Utilization of Care and Preventative Efficacy.
To examine the impact of ethnicity, Spanish language preference, socioeconomic status, and treatment setting on utilization of supportive services before radiotherapy (RT) among head and neck cancer patients and to determine whether a lack of these services is associated with an increased rate of adverse events. Demographic, staging, and treatment details were retrospectively collected for patients treated at a safety-net hospital (n = 56) or adjacent private academic hospital (n = 183) from January 1, 2014, to June 30, 2016. Supportive care services evaluated were limited to speech/swallowing therapy and nutrition therapy. Adverse events and performance measures examined included weight loss during RT, gastric tube placement, emergency department visits, hospital admissions, and missed RT days. On multivariable analysis, patients receiving treatment at the safety-net hospital were less likely to receive speech/swallowing services. Receiving speech/swallowing therapy before treatment was associated with less weight loss during treatment, and in conjunction with nutrition therapy, was associated with fewer missed RT days. Safety-net hospital treatment was associated with a lack of utilization of pre-RT speech/swallowing therapy which in turn was associated with increased weight loss. Interventions aimed at improving utilization of these services would improve treatment tolerance and patient outcomes.


[Neurologic manifestations of chronic arterial insufficiency of the lower extremities].
Neurological manifestations of lower limb chronic arterial insufficiency were studied in 1004 patients with abdominal aorta and its branches occlusion. Several often met neurological syndromes--neuritic, sympathicoalgetic, radicular (mono-, bi- and polyradicular), plexitis lumbosacralis and spinal, induced mainly by regional hemodynamic disturbances were singled out. Clinical peculiarities of these syndromes helping in differentiation of vascular surgical diseases from neurological ones are shown.


Molecular analysis of HIV type 1 vif sequences from Cape Town, South Africa.
South Africa has the highest number of HIV-1-infected individuals in the world, with HIV-1 subtype C prevailing. However, HIV-1 subtype C accessory genes are rarely characterized in the country. These genes are important for establishing viral pathogenesis. The Vif protein has been shown to counteract the antiretroviral activity of APOBEC3G/F cytidine deaminases. In this study an additional 50 HIV-1 vif sequences are characterized. These include 48 HIV-1 subtype C and 2 HIV-1 subtype B sequences. Highly conserved HIV-1 subtype C motifs are outlined. The previously identified RLRR (90-93) motif does not seem to be conserved among our newly analyzed sequences. Conserved motifs can be useful for developing new vaccine strategies or antiretroviral drugs.


Dynamic accommodation measurement using Purkinje reflections and machine learning.
Quantifying eye movement is important for diagnosing various neurological and ocular diseases as well as AR/VR displays. We developed a simple setup for real-time dynamic gaze tracking and accommodation measurements based on Purkinje reflections, which are the reflections from front and back surfaces of the cornea and the eye lens. We used an accurate eye model in ZEMAX to simulate the Purkinje reflection positions at different focus distances of the eye, which matched the experimental data. A neural network was trained to simultaneously predict vergence and accommodation using data collected from 9 subjects. We demonstrated that the use of Purkinje reflection coordinates in machine learning resulted in precise estimation. The proposed system accurately predicted the accommodation with an accuracy better than 0.22 D using subject's own data and 0.40 D using other subjects' data with two-point calibration in tests performed with 9 subjects in our setup.


Opportunistic out-crossing in Nicotiana attenuata (Solanaceae), a predominantly self-fertilizing native tobacco.
Although Nicotiana attenuata is entirely self-compatible, chemical and other floral traits suggest selection for the maintenance of advertisement for moth pollinators. Experimental exclusions of pollinators from plants with emasculated flowers in natural populations in southern Utah during an outbreak of the hawkmoth Hyles lineata revealed that 24% of the seed set could be attributed to insect pollination, and eliminated wind pollination and apomixis as contributing to seed set. Hence these moths can mediate gene flow when self-pollen is unavailable. To quantify gene flow when self-pollen is available, plants were transformed with two marker genes: hygromycin-B resistance and beta-glucuronidase. The utility of these genetic markers to measure gene flow between plants was examined by mixing pollen from plants homozygous for both genes with self-pollen in different ratios and hand-pollinating emasculated flowers of plants growing in a natural population. The proportion of transformed seeds was positively correlated with the amount of transformed pollen applied to stigmas. In glasshouse experiments with the hawkmoth Manduca sexta and experimental arrays of transformed and wild-type plants, pollination mediated by moths accounted for 2.5% of the seed set. Even though moth pollination is rare and highly variable for this largely selfing plant, N. attenuata opportunistically employs a mixed-mating system.


Flexible sample environment for high resolution neutron imaging at high temperatures in controlled atmosphere.
High material penetration by neutrons allows for experiments using sophisticated sample environments providing complex conditions. Thus, neutron imaging holds potential for performing in situ nondestructive measurements on large samples or even full technological systems, which are not possible with any other technique. This paper presents a new sample environment for in situ high resolution neutron imaging experiments at temperatures from room temperature up to 1100 °C and/or using controllable flow of reactive atmospheres. The design also offers the possibility to directly combine imaging with diffraction measurements. Design, special features, and specification of the furnace are described. In addition, examples of experiments successfully performed at various neutron facilities with the furnace, as well as examples of possible applications are presented. This covers a broad field of research from fundamental to technological investigations of various types of materials and components.


Wide vessels sustain marginal transpiration flux and do not optimize inefficient gas exchange activity under impaired hydraulic control and salinity.
Plants optimize water use and carbon assimilation via transient regulation of stomata resistance and by limiting hydraulic conductivity in a long-term response of xylem anatomy. We postulated that without effective hydraulic regulation plants would permanently restrain water loss and photosynthetic productivity under salt stress conditions. We compared wild-type tomatoes to a transgenic type (TT) with impaired stomatal control. Gas exchange activity, biomass, starch content, leaf area and root traits, mineral composition and main stems xylem anatomy and hydraulic conductivity were analyzed in plants exposed to salinities of 1 and 4 dS m-1 over 60 days. As the xylem cannot easily readjust to different environmental conditions, shifts in its anatomy and the permanent effect on plant hydraulic conductivity kept transpiration at lower levels under unstressed conditions and maintained it under salt-stress, while sustaining higher but inefficient assimilation rates, leading to starch accumulation and decreased plant biomass, leaf and root area and root length. Narrow conduits in unstressed TT plants were related to permanent restrain of hydraulic conductivity and plant transpiration. Under salinity, TT plants followed the atmospheric water demand, sustained similar transpiration rate from unstressed to salt-stressed conditions and possibly maintained hydraulic integrity, due to likely impaired hydraulic regulation, wider conduits and higher hydraulic conductivity. The accumulation of salts and starch in the TT plants was a strong evidence of salinity tolerance via osmotic regulation, also thought to help to maintain the assimilation rates and transpiration flux under salinity, although it was not translated into higher growth.


Do awareness-focussed approaches to mitigating diffuse pollution work? A case study using behavioural and water quality evidence.
Efforts to tackle diffuse water pollution from agriculture are increasingly focusing on improving farmers' awareness under the expectation that this would contribute to adoption of best management practices (BMPs) and, in turn, result in water quality improvements. To date, however, no study has explored the full awareness-behaviour-water quality pathway; with previous studies having mostly addressed the awareness-behaviour link relying on disciplinary approaches. Using an interdisciplinary approach, we investigate whether awareness-focussed approaches to mitigating diffuse water pollution from agriculture indeed result in water quality improvement, addressing the pathway in full. We worked with Dŵr Cymru Welsh Water (a water and waste utility company in the UK) on a pesticide pollution intervention programme, referred to as "weed wiper trial". The main goal of the trial was to raise farmers' awareness regarding pesticide management practices and to promote uptake of BMPs to tackle the rising concentrations of the pesticide MCPA (2-methyl-4-chlorophenoxyacetic acid) in raw water in three catchments in Wales. Using factorial analysis of variance, we analysed MCPA concentrations from 2006 to 2019 in the three targeted catchments and in three control catchments. This was followed by semi-structured in-depth interviews with institutional stakeholders and farmers with varying degrees of exposure to the weed wiper trial. Results show that MCPA concentration for both targeted and control catchments had reduced after the implementation of the weed wiper trial. However, the decline was significantly larger (F(1) = 6.551, p < 0.05, n = 3077, Partial eta-squared (ηp2) = 0.002) for the targeted catchments (mean = 45.2%) compared to the control catchments (mean = 10.9%). Results from the stakeholder interviews indicate that improved awareness contributed to changes in farmers' behaviour and that these can be related to the water quality improvements reflected by the decline in MCPA concentration. Alongside awareness, other psychosocial, economic, agronomic factors, catchment and weather conditions also influenced farmer's ability to implement BMPs and thus overall water quality improvements.