Protective action of gastrin-17 against alcohol-induced gastric injury in the rat: role in mucosal defense.
Exogenous cholecystokinin (CCK) or exposure of the stomach to the mild irritant 25% ethanol can prevent gastric injury. Ingestion of ethanol also elicits the release of CCK as well as gastrin, which is structurally similar to CCK. This study was undertaken in conscious rats to examine the gastroprotective actions of gastrin and to assess the effect of CCK-gastrin receptor blockade on adaptive cytoprotection with ethanol as the mild irritant. Intravenous (1-25 pmol/kg) administration of gastrin-17 dose dependently increased gastric mucosal blood flow (laser Doppler) and reduced gastric injury caused by 1 ml of orally administered acidified ethanol (150 mM HCl-50% ethanol). Similar gastroprotection was achieved with the gastrin secretagogue 5% peptone (1 ml orogastrically). The gastroprotective capabilities of gastrin-17 were attenuated by the type B CCK (gastrin) receptor antagonist L-365,260 (12.5-25 mg/kg i.p.) and by capsaicin desensitization (125 mg/kg s.c.). CCK octapeptide (5 nmol/kg i.v.)-induced protection was reversed by the type A CCK receptor antagonist MK-329 (1 mg/kg i.p.). Neither receptor antagonist, alone or in combination, reversed the protective effects of the mild irritant 25% ethanol (1 ml orogastrically). Thus, whereas gastrin may play a role in gastric mucosal defense, neither CCK nor gastrin appears to participate in the phenomenon of adaptive cytoprotection.


Comparative morphology and phylogenetic systematics of the families Cheilodactylidae and Latridae (Perciformes: Cirrhitoidea), and proposal of a new classification.
The phylogenetic relationships of the families Cheilodactylidae and Latridae, plus related taxa, are examined from a detailed osteological perspective. The monophyly of each family is re-evaluated and a new classification is proposed on the basis of phylogenetic relationships. A phylogenetic analysis of characters in 67 transformation series showed Latridae to comprise a monophyletic group nested within cheilodactylids. Cheilodactylidae was non-monophyletic, but rather was formed by a clade including Cheilodactylus fasciatus and C. pixi having a sister relationship with a second clade comprising remaining cheilodactylids and latrids. A new classification is proposed, Cheilodactylidae, including only genus Cheilodactylus, and Latridae, including six genera (Latris, Nemadactylus, Mendosoma, Goniistius, Latridopsis and Dactylophora).


Occurrence of Mycobacterium other than Mycobacterium tuberculosis in the oral cavity and in sputum.
Mycobacteria were cultured from 9% of 424 paired mouthwash-induced sputum specimens. The majority of the organisms were not Mycobacterium tuberculosis. Sputum cultures contributed 59% of these isolations. M. intracellulare was the species most frequently isolated. The non-M. tuberculosis mycobacteria may constitute part of the oral flora of the general population and are not more prevalent in hospitalized patients. Approximately one-third more isolations were made from the patients furnishing two or three pairs of specimens as compared to those patients providing one pair of specimens each. From the paired specimens of 4 of 113 patients, two species of Mycobacterium were isolated. M. intracellulare was isolated from two of three samples of tap water and from the fingers of 1 of 52 patients.


Antiepileptic drugs and relapse after epilepsy surgery.
To evaluate whether the postoperative, antiepileptic drug (AED) regimen influences seizure recurrence after anterior temporal lobectomy when considering the putative mechanism of action and possible neuroprotective effects. This was a retrospective study. Patients who had an anterior temporal lobectomy for refractory epilepsy, whose preoperative MRI indicated mesial temporal sclerosis, were included. Postoperative AED regimens were compared with regard to seizure-outcome, considering the putative mechanism of action (sodium channel blockers, non-sodium channel blockers, and mixed mechanisms) or possible neuroprotective effect (levetiracetam, topiramate, tiagabine and zonisamide versus others). Time-to-event (first seizure after surgery) analysis was used to produce a Kaplan-Meier estimate of seizure recurrence, and groups were compared using Cox proportional hazard analysis. 226 patients (103 males and 123 females; mean age 42 +/- 11 years) were studied. The rates of postoperative seizure recurrence were not significantly different between the three groups regardless of the use of AEDs with different mechanisms of action (p = 0.23). Fifty patients were receiving possibly neuroprotective AEDs and 176 patients were not. Rates of seizure recurrence were not significantly different between these two groups either (p = 0.11). The differences between one-year seizure-free rates were not significant when we compared levetiracetam versus phenytoin or carbamazepine. There appeared to be no advantage or disadvantage to either prescribing drugs with different mechanisms of action or using drugs with possible neuroprotective effect after temporal lobectomy. Prospective studies with larger sample sizes may be of benefit to further explore this issue.


Fast tool for evaluation of iliac crest tissue elastic properties using the reduced-basis methods.
Computationally expensive finite element (FE) methods are generally used for indirect evaluation of tissue mechanical properties of trabecular specimens, which is vital for fracture risk prediction in the elderly. This work presents the application of reduced-basis (RB) methods for rapid evaluation of simulation results. Three cylindrical transiliac crest specimens (diameter: 7.5 mm, length: 10-12 mm) were obtained from healthy subjects (20 year-old, 22 year-old, and 24 year-old females) and scanned using microcomputed tomography imaging. Cubic samples of dimensions 5×5×5 mm(3) were extracted from the core of the cylindrical specimens for FE analysis. Subsequently, a FE solution library (test space) was constructed for each of the specimens by varying the material property parameters: tissue elastic modulus and Poisson's ratio, to develop RB algorithms. The computational speed gain obtained by the RB methods and their accuracy relative to the FE analysis were evaluated. Speed gains greater than 4000 times, were obtained for all three specimens for a loss in accuracy of less than 1% in the maxima of von-Mises stress with respect to the FE-based value. The computational time decreased from more than 6 h to less than 18 s. RB algorithms can be successfully utilized for real-time reliable evaluation of trabecular bone elastic properties.


Daily verbal and nonverbal expression of osteoarthritis pain and spouse responses.
The current study applied a model of pain communication to examine the distinction between verbal and nonverbal pain expression in their prediction of punishing, empathic, and solicitous spouse responses to patient pain. It was hypothesized that on days when patients engaged in more nonverbal expression, spouses would respond more positively (ie, with less punishing and more solicitous and empathic behavior). The same pattern was predicted for verbal expression. In addition, it was expected that associations between patient nonverbal pain expression and positive spouse responses would be strengthened, and that the association with punishing responses would be weakened, on days when levels of verbal pain expression were higher than usual, regardless of daily pain severity. In a 22-day diary study, 144 individuals with knee osteoarthritis and their spouses completed daily measures of pain expression, spouse responses, health, and affect. The predicted positive main effect of nonverbal expression on empathic and solicitous responses was supported by the data, as was the positive main effect for verbal pain expression. Results from moderation analyses partially supported our hypothesis in that patients' nonverbal pain expression was even more strongly related to empathic and solicitous spouse responses on days of high verbal pain expression, and patients were buffered from spouse punishing responses on days when both nonverbal and verbal expression were high. These findings suggest that pain expression in both verbal and nonverbal modes of communication is important for positive and negative spousal responses.


Mid-Regional Proadrenomedullin in COVID-19-May It Act as a Predictor of Prolonged Cardiovascular Complications?
The rising prevalence of cardiovascular disease (CVD) and the impact of the SARS-CoV-2 pandemic have both led to increased mortality rates, affecting public health and the global economy. Therefore, it is essential to find accessible, non-invasive prognostic markers capable of identifying patients at high risk. One encouraging avenue of exploration is the potential of mid-regional proadrenomedullin (MR-proADM) as a biomarker in various health conditions, especially in the context of CVD and COVID-19. MR-proADM presents the ability to predict mortality, heart failure, and adverse outcomes in CVD, offering promise for improved risk assessment and treatment strategies. On the other hand, an elevated MR-proADM level is associated with disease severity and cytokine storms in patients with COVID-19, making it a predictive indicator for intensive care unit admissions and mortality rates. Moreover, MR-proADM may have relevance in long COVID, aiding in the risk assessment, triage, and monitoring of individuals at increased risk of developing prolonged cardiac issues. Our review explores the potential of MR-proADM as a predictor of enduring cardiovascular complications following COVID-19 infection.


Reduced dose of foscarnet as preemptive therapy for cytomegalovirus infection following reduced-intensity cord blood transplantation.
Although foscarnet is a promising alternative for the treatment of cytomegalovirus (CMV) infection, its toxicity can be significant in patients with advanced age. We retrospectively reviewed medical records of 123 patients (median age of 55; range, 17-79) who received reduced-intensity cord blood transplantation (RI-CBT). Patients preemptively received reduced-dose foscarnet 30 mg/kg twice daily when CMV antigenemia exceeded 10/50,000. Sixty-three patients developed CMV antigenemia on a median of day 34, and 29 received foscarnet preemptively. The median level of CMV antigenemia at the initiation of foscarnet was 30. Median duration of foscarnet administration was 24 days. Adverse effects included electrolyte abnormalities (n=19), renal impairment (n=13), and skin eruption requiring discontinuation of foscarnet (n=1). Preemptive therapy of foscarnet was completed in 18 patients. Seven patients died during foscarnet use without developing CMV disease. The remaining 3 developed CMV enterocolitis 5, 14, and 17 days after initiation of foscarnet. All of them were successfully treated with ganciclovir or foscarnet. Reduced dose of foscarnet is beneficial to control CMV reactivation following RI-CBT; however, it has considerable toxicities in RI-CBT recipients with advanced age. Further studies are warranted to minimize toxicities and identify optimal dosages.


Analysis on multifocal contact lens design based on optical power distribution with NURBS.
This paper aims to develop and analyze the design method of multifocal contact lenses to obtain curvature continuity in the optical surfaces with the high addition (Add) powers by adjusting non-uniform rational B-spline (NURBS) curves. The paper has developed mathematical formulae to generate the optical power distributions in which the powers continuously change from either near or distant center to the opposite focal length in the periphery of the optical region with different change rates and Add power values. This developed method can efficiently adjust and optimize three parameters, including control points, weight, and knots of the NURBS, to be anterior optical lens surface profiles to adapt for these given power profiles. The result shows that the proposed contact lenses not only achieve smooth and continuous anterior optical surfaces, but also satisfy various optical power distributions with high Add power values for different pupil diameters. Then, these designs of contact lenses can be feasibly converted to the computer-aided design format for analysis and manufacture for molding or single-point diamond turning. Experimental results of this method have been tested and proven when both the power distributions of simulation of lenses and the actual machined samples match the original specified powers provided by clinical demands of a multifocal contact lens. Future integration with variant clinical demands and optimization rules of lens design can be explored for a progressive contact lens.


Selective sensing of isoprene by Ti-doped ZnO for breath diagnostics.
Exhaled isoprene could enable non-invasive monitoring of cholesterol-lowering therapies. Here, we report an isoprene-selective sensor at high relative humidity (RH) for the first time (to our knowledge). It is made of nanostructured, chemo-resistive Ti-doped ZnO particles (10-20 nm crystal size) produced by flame spray pyrolysis (FSP) and directly deposited in one step onto compact sensor substrates forming highly porous films. The constituent particles consist of stable Ti-doped ZnO solid solutions for Ti levels up to 10 mol% apparently by substitutional incorporation of Ti4+ into the ZnO wurtzite lattice and dominant presence at the particle surface. These Ti4+ point defects strongly enhance the isoprene sensitivity (>15 times higher than pure ZnO) and turn ZnO isoprene-selective, while also improving its thermal stability. In situ infrared spectroscopy confirms that Ti4+ intensifies the surface interaction of Ti-doped ZnO with isoprene by providing additional sites for chemisorbed hydroxyl species. In fact, at an optimal Ti content of 2.5 mol%, this sensor shows superior isoprene responses compared to acetone, NH3 and ethanol at 90% RH. Most notably, breath-relevant isoprene concentrations can be detected accurately down to 5 ppb with high (>10) signal-to-noise ratio. As a result, an inexpensive isoprene detector has been developed that could be easily incorporated into a portable breath analyzer for non-invasive monitoring of metabolic disorders (e.g. cholesterol).


A Proof-of-Concept Study: Simple and Effective Detection of P and T Waves in Arrhythmic ECG Signals.
A robust and numerically-efficient method based on two moving average filters, followed by a dynamic event-related threshold, has been developed to detect P and T waves in electrocardiogram (ECG) signals as a proof-of-concept. Detection of P and T waves is affected by the quality and abnormalities in ECG recordings; the proposed method can detect P and T waves simultaneously through a unique algorithm despite these challenges. The algorithm was tested on arrhythmic ECG signals extracted from the MIT-BIH arrhythmia database with 21,702 beats. These signals typically suffer from: (1) non-stationary effects; (2) low signal-to-noise ratio; (3) premature atrial complexes; (4) premature ventricular complexes; (5) left bundle branch blocks; and (6) right bundle branch blocks. Interestingly, our algorithm obtained a sensitivity of 98.05% and a positive predictivity of 97.11% for P waves, and a sensitivity of 99.86% and a positive predictivity of 99.65% for T waves. These results, combined with the simplicity of the method, demonstrate that an efficient and simple algorithm can suit portable, wearable, and battery-operated ECG devices.


Pathology scoring system for blast injuries.
A pathology scoring system, initially developed by the Walter Reed Army Institute of Research in collaboration with the Lovelace Biomedical and Environmental Research Institute and currently used in the Jaycor Pathos data base program, was modified to arrive at a severity of injury index for individual animals. With this approach, an animal was assessed for injuries by using an alphanumeric code. External lesions, fractures, and trauma to pharynx/larynx, trachea, lungs, heart, hollow abdominal organs, and solid abdominal organs were assigned individual numerical scores based on the severity of the lesion. The various lesions also were graded as trace, slight, moderate, or extensive, depending upon their severity. Each individual score was divided by its preassigned maximum possible score to arrive at a severity of injury ratio for that organ or system. The presence or absence, and the extent of a pneumothorax, hemothorax, hemoperitoneum, coronary air, or cerebral air were summed and added to the sum of the ratios. The resulting value was then multiplied by 1 or 2, depending upon whether the subject was a survivor or a fatality, to arrive at an adjusted severity of injury index by excluding ear damage values from the sum of the ratios. The severity of injury index was used in conjunction with a single degree of freedom blast model to develop damage risk criteria for blast injury.


EMMPRIN/CD147 up-regulates urokinase-type plasminogen activator: implications in oral tumor progression.
An elevated level of EMMPRIN in cancer tissues have been correlated with tumor invasion in numerous cancers including oral cavity and larynx. Although EMMPRIN's effect has been generally attributed to its MMP inducing activity, we have previously demonstrated in breast cancer model that EMMPRIN can also enhance invasion by upregulating uPA. In this study, the role of EMMPRIN in regulating uPA and invasion was investigated in oral squamous cell carcinoma (OSCC) progression. Precancerous and invasive oral tumoral tissues were used as well as the corresponding cell lines, DOK and SCC-9 respectively. The paracrine regulation of uPA by EMMPRIN was investigated by treating culture cells with EMMPRIN-enriched membrane vesicles. UPA expression was analyzed by qPCR and immunostaining and the consequence on the invasion capacity was studied using modified Boyden chamber assay, in the presence or absence of EMMPRIN blocking antibody, the uPA inhibitor amiloride or the MMP inhibitor marimastat. OSCC tumors were shown to express more EMMPRIN and uPA compared to dysplastic lesions. The corresponding cell models, SCC-9 and DOK cells, displayed similar expression pattern. In both cell types EMMPRIN upregulated the expression of uPA as well as that of MMP-2 and MMP-9. EMMPRIN treatment led to a significant increase in cell invasion both in the invasive SCC-9 and in the less invasive dysplastic DOK cells, in an MMP and uPA dependent manner. Our results suggest that the upregulation of uPA contributes to EMMPRIN's effect in promoting oral tumor invasion.


Human immunodeficiency virus infection in Singapore--containment strategies.
The worldwide occurrence of the Acquired Immunodeficiency Syndrome (AIDS) since its advent in the United States in 1981 has resulted in a global dilemma on how best to reduce transmission of the Human Immunodeficiency Virus (HIV). In Singapore, a national AIDS programme was established in 1985 to control the spread of the disease in the country. The programme included health care delivery, education of health care workers and the community, surveillance and counselling of individuals with high risk behaviours, as well as protection of the nation's blood supply. This paper examines the global response to the HIV pandemic and containment strategies appropriate to Singapore based on established epidemiological data.


The use of convalescent plasma for pediatric patients with SARS-CoV-2: A systematic literature review.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease 2019 (COVID-19), a severe illness leading to pneumonia, multiorgan failure, and death. With this study, we performed a systematic review of the literature and ongoing clinical trials on convalescent plasma therapy in pediatric patients with COVID-19. The electronic databases Medline PubMed, Scopus, and Web Of Science were searched. Also, clinical trials registries were searched for potentially eligible studies. A total of 90 records were retrieved after duplicate removal. Eight studies were case reports of children treated with convalescent plasma therapy (14 children, age range, 9 weeks to 18 years); 5 children had a chronic disease. During the hospital stay, 5 received drugs (e.g., remdesivir) in addition to convalescent plasma therapy. No convalescent plasma therapy-related adverse events were reported in 5 studies and 3 made no mention of adverse events. Seven studies concluded that convalescent plasma therapy is or could be a useful therapeutic option; one study made no claims. Only 3 of the 13 retrieved trials underway were planned exclusively for children. This is the first systematic review of the literature regarding convalescent plasma therapy for COVID-19 in children. We found insufficient clinical information on the safety and efficacy of convalescent plasma therapy in children. Nevertheless, the positive outcomes of the few case reports published to date suggest that convalescent plasma therapy may be of potential benefit. Further research with well-designed and powered clinical trials is needed.


Microstructure of neat alcohols: a molecular dynamics study.
Neat methanol and tert-butanol are studied by molecular dynamics with the focus on the microstructure of these two alcohols. The site-site radial distribution functions, the corresponding structure factors, and an effective local one-body density function are shown to be the appropriate statistical quantities that point in a complementary manner towards the same microstructure for any given liquid. Methanol is found to be a weakly associated liquid forming various chainlike patterns (open and closed) while tert-butanol is almost entirely associated and forms micellelike primary pattern. The presence of stable local microheterogeneity within homogeneous disordered phase appears as a striking feature of these liquids. The absence of any such apparent clustering in water--a stronger hydrogen bonding liquid--through the same two statistical quantities is analyzed.


Current status of targeted therapies in advanced gastric cancer.
In metastatic gastric cancer, chemotherapy is the standard treatment because it prolongs survival when compared to best supportive care alone. However, even after the use of more effective regimens, the overall survival remains disappointing, justifying the need for new treatment options. Areas covered in this review include the most common molecular pathways, which have provided novel targets in gastric cancer therapy. These therapeutic strategies include EGFR inhibitors, anti-angiogenic agents, cell cycle inhibitors and apoptosis promoters. Several mAbs and kinase inhibitors, especially those targeting EGFR and VEGF/VEGFR, have already demonstrated promising activity in gastric cancer. The Phase III ToGA trial reported an increase in overall survival for patients with human EGF receptor (HER)2-positive gastric cancer treated with chemotherapy and trastuzumab compared to chemotherapy alone. This means that accurate HER2 testing in gastric cancer is necessary. Final data of ongoing trials with novel agents will be critical to further progress with this cancer.


Novel approaches for myelodysplastic syndromes: beyond hypomethylating agents.
Several novel therapeutic approaches exist for treatment of patients with myelodysplastic syndrome, with goals to improve quality of life and prolong survival. This review highlights new therapies from the last 18 months. Immunosuppressants, erythropoiesis-stimulating agents in combination with granulocyte colony-stimulating factor or all-trans-retinoic-acid have shown improvement in decreasing the need for transfusions and improving quality-of-life and/or survival. Eltrombopag has shown promising results in the treatment of thrombocytopenia. However, determination of an optimal chemotherapeutic approach remains elusive and controversial. DNA methyltransferase inhibitors are well tolerated in outpatient settings, with azacitidine prolonging survival and decreasing time to acute myeloid leukemia progression in patients with high-risk myelodysplastic syndromes. A novel erythroid-specific gene expression profile may predict response to lenalidomide in patients who lack the deletion of 5q31.1. Tools such as the Charlson comorbidity index may help select appropriate patients for allogeneic stem cell transplant. A variety of promising new agents are under investigation. This review focuses on recent advances in new strategies and targeted therapies for treatment of myelodysplastic syndrome.


COVID-19 induces gastrointestinal symptoms and affects patients' prognosis.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection caused the pandemic of coronavirus disease 2019 (COVID-19). Gastrointestinal (GI) involvement is common among patients with COVID-19, and GI symptoms can appear earlier than respiratory symptoms. Except for direct infectious effects, patients infected with SARS-CoV-2 are at risk of complications requiring gastroenterological management. Diarrhea is the most common GI symptom in patients with COVID-19 and occurs in up to half of them. Other GI symptoms, such as anorexia, discomfort, nausea, abdominal pain, loss of taste sensation, and vomiting, have been reported. GI symptoms are associated with a poor prognosis. Fecal viral excretion may have clinical significance because of the possible fecal-oral transmission of infection. In the present narrative review article, six different aspects of studies published to date are summarized as follows: GI manifestations of COVID-19, the roles of fecal-oral transmission, poor prognosis of GI symptoms; abnormal abdominal imaging findings, COVID-19 in patients with irritable bowel disease, and prevention and control of SARS-CoV-2 infection in the digestive endoscopy room. Timely understanding of the association between COVID-19 and the digestive system and effective preventive measures are critical to improve this disease and help clinicians take appropriate measures to mitigate further transmission.


[Urinary stone in a Bricker's ileal conduit].
To report one case of urinary stone as a relatively frequent complications of urinary diversion using bowel loops. We perform a short bibliographic review using the case report format. Stone formation in Bricker's type urinary diversion is secondary to various factors such as urinary stasis, bacteriuria, presence of intestinal mucus, metallic sutures, metabolic disturbances, etc. Periodic control by radiological studies is recommended due to the high frequency of this complication in patients with urinary diversion. Treatment is usually conservative or minimally invasive, being surgery reserved for those cases in which stone extraction is not safe using other methods.


Correlates of cannabis vape-pen use and knowledge among U.S. college students.
The proliferation of electronic devices, such as vape-pens, has provided alternative means for cannabis use. Research has found cannabis-vaping (i.e., vape-pen use) is associated with lower perceived risks and higher cannabis use. Knowledge of these products may increase likelihood of subsequent use. As policies for cannabis shift, beliefs that peers and family approve of this substance use (injunctive norms) increase and there has been an increase in vape-pen use among young adults (18-35 year olds); however, correlates thereof remain unknown. Young adults often engage in cross-substance use with cannabis and alcohol, making alcohol a potential correlate of cannabis vape-pen use and knowledge. Therefore, we examined alcohol use and other potential correlates of vape-pen use and knowledge among a sample of university students. This secondary data analysis utilized surveys at multiple colleges in the U.S. (N = 270). Alcohol use, social anxiety, cannabis expectancies, injunctive and descriptive norms and facets of impulsivity were examined as correlates of vape-pen use and knowledge using bivariate correlations and logistic regressions. Alcohol use was correlated with cannabis vape-pen use and knowledge. Frequency of cannabis use, peer injunctive norms, and positive expectancies were associated with increased likelihood of vape-pen use. Lack of premeditation, a facet of impulsivity, was associated with cannabis vape-pen knowledge. Given the unknown nature and consequences of cannabis vape-pens, the present findings offer valuable information on correlates of this behavior. Further, correlates of knowledge of vape-pens may point to areas for education and clinical intervention to prevent heavy cannabis vape-pen use.


Cerebral blood flow and cognitive responses to rivastigmine treatment in Alzheimer's disease.
Twenty seven patients with mild AD were enrolled in a prospective open label controlled study of rivastigmine. Assessments included a range of neuropsychiatric and behavioural measures and rCBF using HMPAO SPECTat baseline, three and six months. Significant enhancement of frontal, parietal and temporal brain blood flow with related psychometric improvement was observed in twelve of the treated patients. A pattern of reduced rCBF and cognitive performance was observed in four unresponsive and eleven untreated patients. The results suggest that alterations in the clinical and cognitive status of patients receiving a cholinesterase inhibitor are paralleled by changes in rCBF. Longitudinal assessment with repeated imaging offers a method of better understanding the effects of cholinesterase inhibition on the AD brain.


Transplantation of neural stem cells into the modiolus of mouse cochleae injured by cisplatin.
This study aimed to examine the possibility of restoration of spiral ganglion neurons, which transmit sound stimulation to the brain, by transplantation of fetal neural stem cells (NSCs) into the modiolus of cochleae. Fetal mouse NSCs expressing green fluorescence were injected into the modiolus of cisplatin-treated cochleae of mice. The temporal bones were collected 14 days after transplantation, and provided histological examination. The cell fate of transplants was determined by immunohistochemistry for a neural or glial cell-marker. Histological analysis 2 weeks after transplantation revealed robust survival of transplant-derived cells in the modiolus of the cochlea. NSCs injected in the basal portion of cochleae migrated as far as the apical end of the modiolus Grafted NSCs expressing a neural cell marker were identified, but the majority of grafted NSCs differentiated into glial cells. These findings suggest the possible use of NSCs in cell therapy for restoration of spiral ganglion neurons. However, further treatments are required to increase the number of NSC-derived neurons in the modiolus to realize functional recovery.


Rivaroxaban vs. low molecular weight heparin for the prevention of venous thromboembolism after hip or knee arthroplasty: a cohort study.
Rivaroxaban is increasingly used to prevent venous thromboembolism after hip or knee arthroplasty. Studies evaluating the effectiveness of rivaroxaban compared to low molecular weight heparin after orthopedic surgery in routine practice are scarce. We conducted a retrospective cohort study in 121 hospitals in Ontario, Canada, between 2002 and 2012. We included patients aged 66 years or older (median age 73 years) who received an outpatient prescription for subcutaneous low molecular weight heparin (n = 11 471) or oral rivaroxaban (n = 12 850) on hospital discharge after a total knee or hip arthroplasty. The two coprimary outcomes assessed within 30 days of the prescription date were emergency department visit or hospitalization with venous thromboembolism (either deep vein thrombosis or pulmonary embolism; primary efficacy outcome) and a hospitalization with non-traumatic major hemorrhage (primary safety outcome). Rivaroxaban use increased over the study period. Compared to low molecular weight heparin, rivaroxaban was associated with a lower 30-day risk of hospitalization with venous thromboembolism (0.47% vs. 0.81%; relative risk 0.58; 95% confidence interval 0.42-0.81; P = 0.001) with no significant difference in hospitalizations for major bleeding (0.18% vs. 0.20%; relative risk 0.89; 95% confidence interval 0.50-1.59; P = 0.700). In routine practice, anticoagulant prophylaxis with rivaroxaban compared to low molecular weight heparin after hospital discharge from total hip or knee arthroplasty is associated with a lower risk of symptomatic venous thromboembolism with no difference in the risk of bleeding.


Coexpression of IL-18 strongly attenuates IL-12-induced systemic toxicity through a rapid induction of IL-10 without affecting its antitumor capacity.
IL-12 is an excellent candidate for the treatment of cancer due to its ability to drive strong antitumor responses. Recombinant IL-12 protein is currently used in cancer patients; however, systemic expression of rIL-12 presents disadvantages including cost and dose limitation due to its toxicity. In this study, we used hydrodynamic shear of cDNA as a tool to achieve systemic expression of IL-12. We found that sustained but toxic levels of serum IL-12 could be generated in 6- to 7-wk-old B6 mice after a single injection of the cDNA. Unexpectedly, we observed that when IL-12 cDNA is coinjected with IL-18 cDNA, IL-12 antitumor activity was maintained, but there was a significant attenuation of IL-12 toxicity, as evidenced by a greater survival index and a diminution of liver enzymes (ALT and AST). Interestingly, after IL-12 plus IL-18 cDNA administration, more rapid and higher IL-10 levels were observed than after IL-12 cDNA treatment alone. To understand the mechanism of protection, we coinjected IL-12 plus IL-10 cDNAs and observed an increase in survival that correlated with diminished serum levels of the inflammatory cytokines TNF-alpha and IFN-gamma. Confirming the protective role of early IL-10 expression, we observed a significant decrease in survival in IL-10 knockout mice or IL-10R-blocked B6 mice after IL-12 plus IL-18 treatment. Thus, our data demonstrate that the high and early IL-10 expression induced after IL-12 plus IL-18 cDNA treatment is critical to rapidly attenuate IL-12 toxicity without affecting its antitumor capacity. These data could highly contribute to the design of more efficient/less toxic protocols for the treatment of cancer.


Cellular and subcellular localization of enzymes of arginine metabolism in rat kidney.
Rat kidneys extract citrulline derived from the intestinal metabolism of glutamine and convert it stoichiometrically into arginine. This pathway constitutes the major endogenous source of arginine. We investigated the localization of enzymes of arginine synthesis, argininosuccinate synthase and lyase, and of breakdown, arginase and ornithine aminotransferase, in five regions of rat kidney, in cortical tubule fractions and in subcellular fractions of cortex. Argininosuccinate synthase and lyase were found almost exclusively in cortex. Arginase and ornithine aminotransferase were found in inner cortex and outer medulla. Since cortical tissue primarily consists of proximal convoluted and straight tubules, distal tubules and glomeruli, we prepared cortical tubule fragments by collagenase digestion of cortices and fractionated them on a Percoll gradient. Argininosuccinate synthase and lyase were found to be markedly enriched in proximal convoluted tubules, whereas less than 10% of arginase and ornithine aminotransferase, were recovered in this fraction. Arginine production from citrulline was also enriched in proximal convoluted tubules. Subcellular fractionation of kidney cortex revealed that argininosuccinate synthase and lyase are cytosolic. We therefore conclude that arginine synthesis occurs in the cytoplasm of the cells of the proximal convoluted tubule.


Catalytic Potential of Cannabis Prenyltransferase to Expand Cannabinoid Scaffold Diversity.
Biologically active cannabinoids are derived from cannabigerolic acid (CBGA), which is biosynthesized by aromatic prenyltransferase CsPT4. We exploit the catalytic versatility of CsPT4 to synthesize various CBGA analogues, including a geranylated bibenzyl acid, the precursor to bibenzyl cannabinoids of liverwort origin. The synthesized natural and new-to-nature cannabinoids exhibit potent cytotoxicity in human pancreatic cancer cells. CsPT4 can artificially extend the cannabinoid biosynthetic diversity with novel and improved biological activities.


Spontaneous thrombosis of basilar artery aneurysm after subarachnoidal hemorrhage in a patient with thrombophilia and recurrent deep venous thrombosis.
We report a patient with combined thrombophilia--protein C deficiency and mild hyperhomocysteinemia with total spontaneous thrombosis of a basilar tip aneurysm after subarachnoid hemorrhage, without neurological deficit. At admission, the patient had headache, drowsiness, and nausea, with no neurological deficit. Computed tomography (CT) did not show the presence of subarachnoid blood, and magnetic resonance examination revealed discrete remains of a subarachnoid hemorrhage in projections of temporal, frontal and occipital lobes, with no vascular abnormalities. Initial angiography showed a small basilar tip aneurysm and the patient was scheduled for endovascular treatment. A second angiography, performed before the planned endovascular treatment, did not show the aneurysm and complete thrombosis was suspected. A follow-up angiogram, 6 months after this event, showed preserved posterior cerebral circulation with no aneurysm present. The patient was discharged in good condition, without neurological deterioration. We did not find any previous reports of similar conditions.


Spatial and Temporal Patterns of Ross River Virus in Queensland, 2001-2020.
Ross River virus (RRV), the most common human arbovirus infection in Australia, causes significant morbidity and substantial medical costs. About half of Australian cases occur in Queensland. We describe the spatial and temporal patterns of RRV disease in Queensland over the past two decades. RRV notifications, human population data, and weather data from 2001 to 2020 were analysed by the Statistical Area Level 2 (SA2) area. Spatial interpolation or linear extrapolation were used for missing weather values and the estimated population in 2020, respectively. Notifications and incidence rates were analysed through space and time. During the study period, there were 43,699 notifications in Queensland. The highest annual number of notifications was recorded in 2015 (6182), followed by 2020 (3160). The average annual incidence rate was 5 per 10,000 people and the peak period for RRV notifications was March to May. Generally, SA2 areas in northern Queensland had higher numbers of notifications and higher incidence rates than SA2 areas in southern Queensland. The SA2 areas with high incidence rates were in east coastal areas and western Queensland. The timely prediction may aid disease prevention and routine vector control programs, and RRV management plans are important for these areas.


Prognostic significance of p53 gene alterations in node-negative breast cancer.
Mutations in the p53 gene can play a role in the transformation of normal to malignant cells. Because these mutations are more frequently reported later in the course of transformation, their presence could reflect a greater malignant potential of the tumor and, thus, an increased probability of metastasis and recurrence after local therapy. In a pilot study using single-stranded conformation polymorphism analysis (SSCP), 200 node-negative breast tumors were examined for mutations in the region encompassing exons 5 through 9 of the p53 gene. Exons 5 through 9 were tested because they contain 80-90% of known p53 gene mutations. The tumors ranged in size from 1 to 3 cm. 28 tumors were found to have an abnormal band pattern on both initial and repeat analysis. 4 of these tumors were sequenced; 3 contained a p53 mutation and the 4th had a rare neutral polymorphism. Disease-free survival (DFS) at 5 years for women with tumors having an abnormal SSCP analysis was 57% (+/- 10%), compared to a 79% (+/- 3%) DFS for the group with a normal pattern. By the log rank test, this difference was highly significant, p < or = 0.01. The relative risk of recurrence for the group with an abnormal SSCP pattern was 2.2. In a multivariate analysis including ER, PgR, ploidy, S-phase, age, and tumor size, an abnormal p53 by SSCP analysis and patient age were the only factors that independently predicted DFS at 5 years. Women with node-negative breast cancer who have tumors with alterations in the p53 gene, as indicated by SSCP analysis, have a significantly poorer prognosis and a higher rate of relapse at 5 years. The prognostic significance is maintained in a multivariate analysis including many established prognostic factors.


Synaptic theory of replicator-like melioration.
According to the theory of Melioration, organisms in repeated choice settings shift their choice preference in favor of the alternative that provides the highest return. The goal of this paper is to explain how this learning behavior can emerge from microscopic changes in the efficacies of synapses, in the context of a two-alternative repeated-choice experiment. I consider a large family of synaptic plasticity rules in which changes in synaptic efficacies are driven by the covariance between reward and neural activity. I construct a general framework that predicts the learning dynamics of any decision-making neural network that implements this synaptic plasticity rule and show that melioration naturally emerges in such networks. Moreover, the resultant learning dynamics follows the Replicator equation which is commonly used to phenomenologically describe changes in behavior in operant conditioning experiments. Several examples demonstrate how the learning rate of the network is affected by its properties and by the specifics of the plasticity rule. These results help bridge the gap between cellular physiology and learning behavior.


Continuous Manufacturing of Pharmaceutical Products: A Density-Insensitive Near Infrared Method for the In-line Monitoring of Continuous Powder Streams.
Near infrared (NIR) spectroscopy is a valuable analytical technique for monitoring chemical composition of powder blends in continuous pharmaceutical processes. However, the variation in density captured by NIR during spectral collection of dynamic powder streams at different flow rates often reduces the performance and robustness of NIR models. To overcome this challenge, quantitative NIR measurements are commonly collected across all potential manufacturing conditions, including multiple flow rates to account for the physical variations. The utility of this approach is limited by the considerable quantity of resources required to run and analyze an extensive calibration design at variable flow rates in a continuous manufacturing (CM) process. It is hypothesized that the primary variation introduced to NIR spectra from changing flow rates is a change in the density of the powder from which NIR spectra are collected. In this work, powder stream density was used as an efficient surrogate for flow rate in developing a quantitative NIR method with enhanced robustness against process rate variation. A density design space of two process parameters was generated to determine the conditions required to encompass the apparent density and spectral variance from increases in process rate. This apparent density variance was included in calibration at a constant low flow rate to enable the development of a density-insensitive NIR quantitative model with limited consumption of materials. The density-insensitive NIR model demonstrated comparable prediction performance and flow rate robustness to a traditional NIR model including flow rate variation ("gold standard" model) when applied to monitoring drug content in continuous runs at varying flow rates. The proposed platform for the development of in-line density-insensitive NIR methods is expected to facilitate robust analytical model performance across variable continuous manufacturing production scales while improving the material efficiency over traditional robust modeling approaches for calibration development.


Applying a new concept of embedding qualitative research: an example from a quantitative study of carers of people in later stage dementia.
Qualitative methods are increasingly included in larger studies to provide a richer understanding of people's experience. This paper explores the potential of using a novel approach to embedded qualitative design as part of an observational study examining the effectiveness of home support for people in later stage dementia in England. The method involved collecting and analysing unsolicited conversational comments made by participants as they completed standardised measures. An evaluation of the method is presented using the voices of participants to illustrate its potential. The conversations of 17 carers recruited to an observational study were audio recorded to gather commentary made while completing a structured interview. Data were interrogated using thematic analysis to investigate the feasibility of conducting an embedded qualitative study, the potential richness of the material and participants' reactions to formal questioning and participating in research. The findings revealed that qualitative data were available from this approach. Analysis generated three themes from carers: conflicting carer emotions; the importance of maintaining normality and agency within day-to-day life; and tensions between these desires and making use of formal services. Important issues for carers were revealed establishing the benefit of using the method. The advantages of exploiting unsolicited conversation included enhancing understanding of people's lived experience, reducing participant burden in research and easing the process of data collection. In addition, it provided an opportunity to evaluate individuals' experience of the research process. The findings demonstrate how unsolicited comments during structured interviews may appear incidental but can reveal important aspects of living with dementia. The method also emphasised methodological challenges for research in dementia, including the influence and impact of the research context. Further research is required to evaluate the method with other groups including people with dementia themselves.


Neural mechanisms for the effect of prior knowledge on audiovisual integration.
Converging evidence indicates that prior knowledge plays an important role in multisensory integration. However, the neural mechanisms underlying the processes with which prior knowledge is integrated with current sensory information remains unknown. In this study, we measured event-related potentials (ERPs) while manipulating prior knowledge using a novel visual letter recognition task in which auditory information was always presented simultaneously. The color of the letters was assigned to a particular probability of being associated with audiovisual congruency (e.g., green=high probability (HP) and blue=low probability (LP)). Results demonstrate that this prior began affecting reaction times to the congruent audiovisual stimuli at about the 900th trial. Consequently, the ERP data was analyzed in two phases: the "early phase" (<trial 600) and the "late phase" (>trial 900). The effects of prior knowledge were revealed through difference waveforms generated by subtracting the ERPs for the congruent audiovisual stimuli in the LP condition from those in the HP condition. A frontal-central probability effect (90-120 ms) was observed in the early phase. A right parietal-occipital probability effect (40-96 ms) and a frontal-central probability effect (170-200 ms) were observed in the late phase. The results suggest that during the initial acquisition of the knowledge about the probability of congruency, the brain assigned more attention to audiovisual stimuli for the LP condition. Following the acquisition of this prior knowledge, it was then used during early stages of visual processing and modulated the activity of multisensory cortical areas.


ASAS centennial paper: Lactation biology for the twenty-first century.
Knowledge of general aspects of mammary gland function, including metabolic pathways and hormonal regulation of mammary gland development and lactation, in livestock species was obtained several decades ago. As basic biological information of growth factor action, apoptotic mechanisms, and signal transduction events has exploded, the mouse became the model of choice for studying fundamental mechanisms regulating mammary function. A complete sequenced genome also has made the mouse amenable for studies of mammary gene network expression. Advances in molecular biology techniques currently allow researchers to genetically modify mice to either overexpress or completely lack specific genes, thereby studying their function in an in vivo setting. Furthermore, the use of mammary-specific promoters has allowed genes related to mammary gland function to be eliminated from the mammary gland in a developmental and tissue-specific manner. These studies have demonstrated the complexity that underlies mammary gland development and function in rodents and may provide insight into the mechanisms that ultimately allow the ruminant or swine mammary gland to function in a coordinated fashion throughout puberty, pregnancy, lactation, and involution. The challenge facing animal scientists is how to obtain similar information in much larger and expensive livestock. One possible approach is to manipulate gene expression in vitro using mammary cell culture models derived from domestic animals (e.g., genes can be "knocked down" using small interfering RNA approaches). Ultimately, major advances in understanding lactation biology may come from coupling basic mechanistic information with functional genomics, proteomics, and metabolomics approaches. A strong foundation in bioinformatics will also be required to optimize use of these new technologies. Stem cell biology also represents an exciting area in the next decade that holds promise for improving lactation efficiency. Strong training of our future scientists in these areas should facilitate livestock-focused mammary gland research that will allow basic information to be gained at unprecedented amounts, ultimately leading to optimization of livestock production.


Health Effects of an Individualized Lifestyle Intervention for People with Psychotic Disorders in Psychiatric Outpatient Services: A Two Year Follow-up.
People with psychotic disorders experience to a great extent avoidable physical illnesses and early mortality. The aim of the study was to investigate the potential effects for this group of participating in a lifestyle intervention. A multi-component nurse-led lifestyle intervention using quasi-experimental design was performed. Changes in biomedical and clinical measurements, self-reported health, symptoms of illness and health behavior were investigated. Multilevel modeling was used to statistically test differences in changes over time. Statistically significant changes were found in physical activity, HbA1c and waist circumference. A lifestyle intervention for people with severe mental illness can be beneficial for increasing physical activity.


Nonretinoid chaperones improve rhodopsin homeostasis in a mouse model of retinitis pigmentosa.
Rhodopsin-associated (RHO-associated) retinitis pigmentosa (RP) is a progressive retinal disease that currently has no cure. RHO protein misfolding leads to disturbed proteostasis and the death of rod photoreceptors, resulting in decreased vision. We previously identified nonretinoid chaperones of RHO, including YC-001 and F5257-0462, by small-molecule high-throughput screening. Here, we profile the chaperone activities of these molecules toward the cell-surface level of 27 RP-causing human RHO mutants in NIH3T3 cells. Furthermore, using retinal explant culture, we show that YC-001 improves retinal proteostasis by supporting RHO homeostasis in RhoP23H/+ mouse retinae, which results in thicker outer nuclear layers (ONL), indicating delayed photoreceptor degeneration. Interestingly, YC-001 ameliorated retinal immune responses and reduced the number of microglia/macrophages in the RhoP23H/+ retinal explants. Similarly, F5257-0462 also protects photoreceptors in RhoP23H/+ retinal explants. In vivo, intravitreal injection of YC-001 or F5257-0462 microparticles in PBS shows that F5257-0462 has a higher efficacy in preserving photoreceptor function and delaying photoreceptor death in RhoP23H/+ mice. Collectively, we provide proof of principle that nonretinoid chaperones are promising drug candidates in treating RHO-associated RP.


Chemokine interactome mapping enables tailored intervention in acute and chronic inflammation.
Chemokines orchestrate leukocyte trafficking and function in health and disease. Heterophilic interactions between chemokines in a given microenvironment may amplify, inhibit, or modulate their activity; however, a systematic evaluation of the chemokine interactome has not been performed. We used immunoligand blotting and surface plasmon resonance to obtain a comprehensive map of chemokine-chemokine interactions and to confirm their specificity. Structure-function analyses revealed that chemokine activity can be enhanced by CC-type heterodimers but inhibited by CXC-type heterodimers. Functional synergism was achieved through receptor heteromerization induced by CCL5-CCL17 or receptor retention at the cell surface via auxiliary proteoglycan binding of CCL5-CXCL4. In contrast, inhibitory activity relied on conformational changes (in CXCL12), affecting receptor signaling. Obligate CC-type heterodimers showed high efficacy and potency and drove acute lung injury and atherosclerosis, processes abrogated by specific CCL5-derived peptide inhibitors or knock-in of an interaction-deficient CXCL4 variant. Atheroprotective effects of CCL17 deficiency were phenocopied by a CCL5-derived peptide disrupting CCL5-CCL17 heterodimers, whereas a CCL5 α-helix peptide mimicked inhibitory effects on CXCL12-driven platelet aggregation. Thus, formation of specific chemokine heterodimers differentially dictates functional activity and can be exploited for therapeutic targeting.


Growth and development of a new subspecialty: pediatric hepatology.
Several major forces converged to catalyze the formal emergence of a body of knowledge and an organized focus on disorders of the liver in early life. Attendant to the development of a focused clinical subspecialty the pace of patient- and laboratory-based research in the field quickened in parallel to decipher the consequences of genetic or metabolic aberrations on immature liver structure and function. The key research observations that catalyzed the emergence and subsequent rapid growth of Pediatric Hepatology include: (1) an understanding of the dynamic events occurring during hepatobiliary development and the importance of these physiologic variables that occur during liver maturation; (2) the recognition of the unique nature of inherited and acquired liver diseases that affect infants and children-such as biliary atresia and Reye's syndrome; and (3) redefinition of the once obscure inherited intrahepatic cholestatic diseases of the liver, which, in turn, provided insight into normal and abnormal hepatobiliary physiology. The clinical advances were highlighted by the development of specific approaches to the diagnosis and management of liver disease in infants and children, including both liver transplantation and nontransplant treatment options. These seminal events led to the expansion of the workforce, creating a critical mass consisting of individuals with focused, specialized skills and techniques. In-depth expertise allowed more accurate diagnosis and highly effective treatment strategies for advanced hepatobiliary disease in children. The demand for pediatric clinicians with experience in advanced hepatology allowed sub-sub-specialization to flourish. Continued maturation of the field led to definition of hepatology-focused curricular elements and educational content for Pediatric Gastroenterology training programs, and subsequently the development of program requirements for those who wished to acquire additional training in Pediatric Hepatology. A significant rite of passage was marked by the election of pediatric hepatologists to leadership positions in the American Association for the Study of Liver Diseases (AASLD). Further validation of the field occurred with approval of the petition for establishing a Certificate of Added Qualification in Transplant Hepatology by the American Board of Pediatrics. Here I relate my perspective on the history of the advances in our field and the contributions of many of the clinicians and scientists whose efforts led to the development of focused clinical, research, and training programs that improved the care of children with diseases of the liver.


The mutation at nt 8993 of mitochondrial DNA is a common cause of Leigh's syndrome.
Twelve patients with Leigh's syndrome from 10 families harbored a T > G point mutation at nt 8993 of mtDNA. This mutation, initially associated with neurogenic weakness, ataxia, and retinitis pigmentosa, was later found to result in the Leigh phenotype when present in a high percentage. In our patients, the mutation was heteroplasmic, maternally inherited, and appeared to segregate rapidly within the pedigrees. Quantitative analysis revealed a good correlation between percentage of mutant mitochondrial genomes and severity of the clinical phenotype. The mutation was not found in > 200 patients with other mitochondrial encephalomyopathies or in controls. Mitochondrial enzyme activities were normal in all but 1 patient, and there were no ragged-red fibers in the muscle biopsy. Lactic acidosis was present in 92% of patients. Our findings suggest that the mtDNA nt 8993 mutation is a relatively common cause of Leigh's syndrome.


Transcranial direct current stimulation of the primary motor cortex improves word-retrieval in older adults.
Language facilitation by transcranial direct current stimulation (tDCS) in healthy individuals has generated hope that tDCS may also allow improving language impairment after stroke (aphasia). However, current stimulation protocols have yielded variable results and may require identification of residual language cortex using functional magnetic resonance imaging (fMRI), which complicates incorporation into clinical practice. Based on previous behavioral studies that demonstrated improved language processing by motor system pre-activation, the present study assessed whether tDCS administered to the primary motor cortex (M1) can enhance language functions. This proof-of-concept study employed a sham-tDCS controlled, cross-over, within-subject design and assessed the impact of unilateral excitatory (anodal) and bihemispheric (dual) tDCS in 18 healthy older adults during semantic word-retrieval and motor speech tasks. Simultaneous fMRI scrutinized the neural mechanisms underlying tDCS effects. Both active tDCS conditions significantly improved word-retrieval compared to sham-tDCS. The direct comparison of activity elicited by word-retrieval vs. motor-speech trials revealed bilateral frontal activity increases during both anodal- and dual-tDCS compared to sham-tDCS. This effect was driven by more pronounced deactivation of frontal regions during the motor-speech task, while activity during word-retrieval trials was unaffected by the stimulation. No effects were found in M1 and secondary motor regions. Our results show that tDCS administered to M1 can improve word-retrieval in healthy individuals, thereby providing a rationale to explore whether M1-tDCS may offer a novel approach to improve language functions in aphasia. Functional magnetic resonance imaging revealed neural facilitation specifically during motor speech trials, which may have reduced switching costs between the overlapping neural systems for lexical retrieval and speech processing, thereby resulting in improved performance.


DNA amplification.
The polymerase chain reaction has become a mainstream tool for the molecular biologist. The sensitivity, efficiency, and speed of this method is unparalleled for the amplification and detection of exquisitely minute quantities of nucleic acids. Through repetitive cycles of heat denaturation of samples, followed by the base pairing of primers designed to identify one DNA sequence among the cellular heterogeneity, and finally synthesis of new DNA strands identical to the target, single molecules and individual genes can be detected and subsequently characterized. This method has revolutionized the study of gene organization, structure, and expression, not to mention offering newer, faster, and more economical means for the clinical detection infectious disease. That PCR has been fruitful is undisputed; however, the method is not without shortcomings. Among the major limitations of this method are the absolute requirement for well-designed primers, the super sensitivity of this method to biological contaminants from any of a variety of sources, and subtle, though very important, inter- and intra-laboratory variations in technique.


Effect of gender on the etiology of fecal incontinence: Retrospective analysis of a tertiary referral center in Turkey.
Anorectal diseases, including fecal incontinence, are prevalent and have an enormous impact on the quality of life. Therefore, investigating their etiological factors may help to reduce the incidence and/or the severity of the underlying diseases. Referral complaints (constipation, strained defecation, and incontinence) and medical and anorectal manometry records of 883 (562 female/321 male, ages 45.17±1.00 and 48.41±0.63 years, respectively) patients were evaluated retrospectively. Maximal resting pressure (MRP) and maximal squeeze pressure (MSP) measured by stationary pull-through technique, volume of rectoanal inhibitory reflex, and sensory threshold to rectal balloon distention (ST) were obtained by water perfusion system. Data were compared according to referral complaints, age, gender, parity, and underlying diseases. Incontinence was the most frequent referral complaint in 61.2% of females and 67.6% of males. MRP and MSP were significantly lower in incontinent females than in the other groups. In incontinent males, MSP was lower than the strained defecation group, and ST was higher than the constipation group. Age was negatively correlated with MRP for both of the genders and in all groups. Obstetric trauma (85%) and number of parity (3.40±2.59) were significantly higher in incontinent females. Moreover, the most prevalent underlying disease was diabetes in incontinent females (13.7%) and neurological diseases, including traumas, in incontinent males (41.5%). Increasing awareness of labor safety, controlling diabetes mellitus, and preventing obstetric traumas may reduce the prevalence of fecal incontinence.


The 5-enolpyruvylshikimate-3-phosphate synthase of glyphosate-tolerant soybean expressed in Escherichia coli shows no severe allergenicity.
The recombinant gene was amplified from the chromosomal DNA of genetically-modified (GM) soybeans and identified as epsps encoding 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) which renders glyphosate resistance. The epsps structural gene was introduced in the pET28(a) plasmid for its expression in Escherichia coli BL21(DE3). It was confirmed that the maximal productivity of the EPSPS protein was achieved when cultivating the recombinant strain in a LB broth for 2 h after supplementing 1 mM isopropylbeta-D-thiogalactopyranoside (IPTG) in a 2 h-culture broth. Since the expressed EPSPS protein was found as an insoluble form in the inclusion body, it was extracted by 6 M urea after sonication, and then purified through immobilized nickel-affinity column chromatography to isolate EPSPS having a molecular mass of 57 kDa. When incubated in simulated gastric fluid containing pepsin at pH 1.5, the purified EPSPS protein was completely digested within 1 min. In addition, the passive cutaneous anaphylaxis reaction of the purified EPSPS protein was not observed in the Sprague Dawley rat system that was administered either orally or subcutaneously. Furthermore, treatment of the EPSPS protein to the culture of the sensitized peritoneal mast cells, or unsensitized but antisera-labeled mast cells, showed neither a remarkable change in the histamine release nor a cytokine production, including interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-alpha). Thus, it can be concluded that the EPSPS protein in the GM soybean showed no significant allergenicity in the Sprague Dawley rats.


From maternal tending to adolescent befriending: The adolescent transition of social support.
Attachment theory holds that parental relationships have lifelong effects on offspring social lives. The tend-and-befriend hypothesis posits that female friendships among humans evolved as part of a primate-wide coping mechanism to mediate stress by relying on social support. Here we bridge developmental and evolutionary frameworks to examine adolescent girls' perception of their reliance on female friendship for social support, how perceptions of parental relationships affect peer relationships, and the extent to which parent and peer relationships buffer depressive symptoms. We predict perceived maternal relationship quality will be positively associated with close female friendships, and maternal relationships, paternal relationships, and female friendship will buffer depressive symptoms. Participants were adolescent girls from a summer science camp (N = 95). Participants filled out demographic information, social network surveys, the Parent-Adolescent Communication Scale, and the Center for Epidemiology Depression Scale. Data was analyzed with Pearson's correlations, t tests, and path analysis. Adolescent girls with few female friends, compared with girls who had more than two very close female friends, experienced more depressive symptoms (t = 3.382, p = .001, D = 0.784). Adolescent girls with few female friends experienced more depressive symptoms compared to girls with two or more very close female friends (t = 3.382, p = .001, D = 0.784). Stronger maternal and paternal relationships were associated with having more female friends (maternal: t = -3.213, p = .003, D = 0.837; paternal: t = -2.432; p = .017). In the path analysis model, only maternal relationship quality significantly predicted female friendship category (β = .33, CR = 2.770, p < .006). Furthermore, participants with two or more very close female friends and higher paternal relationship quality had significantly fewer depressive symptoms (friends; β = -.19, CR = -2.112, p = .035; paternal: β = -.33, CR = -3.220, p < .001), and older participants had more depressive symptoms (β = .17, CR = -1.931, p = .036). These results provide additional support for the tend-and-befriend hypothesis, suggesting that maternal tending sets the stage for close female friendships.


Adsorption Properties and Mechanism of Cd2+ in Water by Zr-containing Silica Residue Purification.
Zirconium (Zr)-containing silica residue purification (ZSR-P) discharged from industrial production of ZrOCl2 was used as an adsorbent, and CdCl2 solution was used as the simulated wastewater containing cadmium ions (Cd2+). The properties and mechanisms of ZSR-P absorbing Cd2+ were studied. The results showed that ZSR-P had a good effect on the adsorption and removal of Cd2+ in water. The adsorption time, initial concentration of Cd2+, and pH of the solution had a significant effect on the adsorption behavior, whilst the pH value had the greatest effect amongst them. Under optimal conditions, the amount of Cd2+ adsorbed by ZSR-P was 43.1 mg/g. The isothermal adsorption conformed to the Langmuir adsorption model, and the adsorption kinetics conformed to the secondary adsorption rate model. In ZSR-P-Cd, Cd2+ was uniformly distributed on the surface of SiO2 particles and in the pores formed by the accumulation of particles. Adsorption of Cd2+ by ZSR-P was achieved through the reaction between Si-OH on the surface of SiO2 and Cd2+ hydroxyl compounds.


Successful training of HEMS personnel in laryngeal mask airway and intubating laryngeal mask airway placement.
To evaluate laryngeal mask airway (LMA) and intubating laryngeal mask airway (ILMA) placement by helicopter emergency medical services (HEMS) personnel after a comprehensive training program. HEMS flight staff attended a didactic and manikin-based training session for both devices. After this training, they attempted LMA and ILMA placement in live, anesthetized patients in an operating room (OR). Outcome measures included placement success rates with the LMA, ILMA, and endotracheal intubation through the ILMA, time to ventilation, and time to intubation. Success rates and time to ventilation were compared using chi-squared and analysis of variance (ANOVA), respectively. Mean time to ventilation for the first and second placements of both devices was examined with repeated measures ANOVA. There was no difference in successful placement of the LMA compared with the ILMA (100% vs. 91%, P = .15). Ninety-five percent (19/20) of patients were successfully intubated through the ILMA. Time to intubation was 57.1 +/- 55 seconds (range, 20-240). Mean time to ventilation with either device did not differ significantly (36.8 +/- 17 vs. 38.05 +/- 20 seconds; P = .29). Mean time to ventilation for the first and second placement of either the LMA (P = .45) or the ILMA (P = .47) was not statistically different. Trained HEMS flight staff are capable of effectively placing the LMA and ILMA in the operating room after a comprehensive training protocol.


Placenta-on-a-chip: a novel platform to study the biology of the human placenta.
Studying the biology of the human placenta represents a major experimental challenge. Although conventional cell culture techniques have been used to study different types of placenta-derived cells, current in vitro models have limitations in recapitulating organ-specific structure and key physiological functions of the placenta. Here we demonstrate that it is possible to leverage microfluidic and microfabrication technologies to develop a microengineered biomimetic model that replicates the architecture and function of the placenta. A "Placenta-on-a-Chip" microdevice was created by using a set of soft elastomer-based microfabrication techniques known as soft lithography. This microsystem consisted of two polydimethylsiloxane (PDMS) microfluidic channels separated by a thin extracellular matrix (ECM) membrane. To reproduce the placental barrier in this model, human trophoblasts (JEG-3) and human umbilical vein endothelial cells (HUVECs) were seeded onto the opposite sides of the ECM membrane and cultured under dynamic flow conditions to form confluent epithelial and endothelial layers in close apposition. We tested the physiological function of the microengineered placental barrier by measuring glucose transport across the trophoblast-endothelial interface over time. The permeability of the barrier study was analyzed and compared to that obtained from acellular devices and additional control groups that contained epithelial or endothelial layers alone. Our microfluidic cell culture system provided a tightly controlled fluidic environment conducive to the proliferation and maintenance of JEG-3 trophoblasts and HUVECs on the ECM scaffold. Prolonged culture in this model produced confluent cellular monolayers on the intervening membrane that together formed the placental barrier. This in vivo-like microarchitecture was also critical for creating a physiologically relevant effective barrier to glucose transport. Quantitative investigation of barrier function was conducted by calculating permeability coefficients and metabolic rates in varying conditions of barrier structure. The rates of glucose transport and metabolism were consistent with previously reported in vivo observations. The "Placenta-on-a-Chip" microdevice described herein provides new opportunities to simulate and analyze critical physiological responses of the placental barrier. This system may be used to address the major limitations of existing placenta model systems and serve to enable research platforms for reproductive biology and medicine.


Defiance, compliance, or alliance? How we developed a medical professionalism curriculum that deliberately connects to cultural context.
In the age of globalization, non-Western medical educators seem too eager to conform to Western educational approaches and may, thereby, undermine the pursuit of local curricular needs. To develop a medical professionalism curriculum that explicitly considered local cultural needs and social expectations. We used a systematic six-step approach to develop the curriculum. We engaged local stakeholders (physicians, allied health professionals, and members of the public) in a nominal group process to identify professionalism competencies. Students and faculty participated in a survey and/or focus groups to determine learner/faculty needs. Teachers drafted goals and objectives related to locally valued competencies. We designed and implemented educational strategies to develop students' competencies that meet local societal expectations, such as involving family members in decision making. We plan to use multi-source feedback and a portfolio to assess students, which reinforces a definition of integrity that encompasses not only congruence between individual values and behaviors, but also achieving harmony among all stakeholders. We plan to reinforce the formal curriculum with faculty development and attention to the hidden curriculum. Based upon our experience and reflection, we offer some practical methods for integrating local cultural values and societal needs in professionalism education.


Characterization of Sp-5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole- 3',5'-monophosphorothioate (Sp-5,6-DCl-cBiMPS) as a potent and specific activator of cyclic-AMP-dependent protein kinase in cell extracts and intact cells.
A newly designed cyclic AMP (cAMP) analogue, Sp-5,6-dichloro-1-beta-D- ribofuranosylbenzimidazole-3',5'-monophosphorothioate (Sp-5,6-DCl-cBiMPS), and 8-(p-chlorophenylthio)-cAMP (8-pCPT-cAMP) were compared with respect to their chemical and biological properties in order to assess their potential as activators of the cAMP-dependent protein kinases (cAMP-PK) in intact cells. Sp-5,6-DCl-cBiMPS was shown to be both a potent and specific activator of purified cAMP-PK and of cAMP-PK in platelet membranes, whereas 8-pCPT-cAMP proved to be a potent activator of cAMP-PK and cyclic-GMP-dependent protein kinase (cGMP-PK) both as purified enzymes and in platelet membranes. Sp-5,6-DCl-cBiMPS was not significantly hydrolysed by three types of cyclic nucleotide phosphodiesterases, whereas 8-pCPT-cAMP (and 8-bromo-cAMP) was hydrolysed to a significant extent by the Ca2+/calmodulin-dependent phosphodiesterase and by the cGMP-inhibited phosphodiesterase. The apparent lipophilicity, a measure of potential cell-membrane permeability, of Sp-5,6-DCl-cBiMPS was higher than that of 8-pCPT-cAMP. Extracellular application of Sp-5,6-DCl-cBiMPS to intact human platelets reproduced the pattern of protein phosphorylation induced by prostaglandin E1, a cAMP-increasing inhibitor of platelet activation. In intact platelets, Sp-5,6- DCl-cBiMPS was also more effective than 8-pCPT-cAMP in inducing quantitative phosphorylation of the 46/50 kDa vasodilator-stimulated phosphoprotein (VASP), a major substrate of cAMP-PK in platelets. As observed with prostaglandin E1, pretreatment of human platelets with Sp-5,6-DCl-cBiMPS prevented the aggregation induced by thrombin. The results suggest that Sp-5,6-DCl-cBiMPS is a very potent and specific activator of cAMP-PK in cell extracts and intact cells and, in this respect, is superior to any other cAMP analogue used for intact-cell studies. In contrast with 8-pCPT-cAMP, Sp-5,6-DCl-cBiMPS can be used to distinguish the signal-transduction pathways mediated by cAMP-PK and cGMP-PK.


Omitting the intra-session calibration in EEG-based brain computer interface used for stroke rehabilitation.
Brain-computer interface (BCI) as a rehabilitation tool has been used in restoring motor functions in patients with moderate to sever stroke impairments. To achieve the best possible outcome in such an application, it is highly desirable to have a stable and accurate operation of BCI. However, since electroencephalogram (EEG) signals considerably vary between sessions of even the same user, typically a long calibration session is recorded at the beginning of each session. This process is time-consuming and inconvenient for stroke patients who undergo long-term BCI sessions with repeating same mental tasks. This paper investigates the possibility of omitting the intra-session calibration for BCI-based stroke rehabilitation when large data recorded from the same user are available. For this purpose, a large dataset of EEG signals from 11 stroke patients performing 12 BCI-based stroke rehabilitation sessions over one month is used. Our offline results suggest that after recording a number of stroke rehabilitation sessions, the patient does not require calibration any more. The experimental results show that combining 11 sessions, which each session comprises minimum 60 trials per class, yields a model that averagely outperforms the standard calibration model trained by the data recorded directly before the test session.


Mitral valve disease in Marfan syndrome and related disorders.
Marfan syndrome (MFS) is a systemic disorder of the connective tissue with pleiotropic manifestations due to heterozygous FBN1 mutations and consequent upregulation of TGFβ signaling in affected tissues. Myxomatous thickening and elongation of the mitral valve (MV) leaflets commonly occur in this condition. Investigation of murine models of this disease has led to improved understanding of the mechanisms that underlie many of the phenotypic features of MFS, including MV disease. Loeys-Dietz syndrome (LDS) is a related disorder due to heterozygous mutations in the genes encoding subunits of the TGFβ receptor, and it may also involve the MV leaflets with similar elongation and thickening of the MV leaflets. Although the genetic basis and pathogenesis of nonsyndromic MV prolapse has been elusive to date, insights derived from monogenic disorders like MFS and LDS can be informative with regard to novel gene discovery and investigation into the pathogenesis of MV disease. This manuscript will review the prevalence of MV disease in MFS, its pathogenic basis as determined in mice with Fbn1 mutations, and ongoing studies that seek to better understand MV disease in the context of fibrillin-1 deficiency or excessive TGFβ signaling.


Viral Encephalopathy and Retinopathy in groupers (Epinephelus spp.) in southern Italy: a threat for wild endangered species?
Betanodaviruses are the causative agents of Viral Encephalopathy and Retinopathy (VER). To date, more than 50 species have proved to be susceptible and among them, those found in genus Epinephelus are highly represented. Clinical disease outbreaks are generally characterized by typical nervous signs and significant mortalities mainly associated with aquaculture activities, although some concerns for the impact of this infection in wild fish have been raised. In this study, the authors present the first documented report describing an outbreak of VER in wild species in the Mediterranean basin. In late summer--early winter 2011 (September-December), significant mortalities affecting wild Dusky grouper (Epinephelus marginatus), Golden grouper (Epinephelus costae) and European sea bass (Dicentrarchus labrax) were reported in the municipality of Santa Maria di Leuca (Northern Ionian Sea, Italy). The affected fish showed an abnormal swimming behavior and swollen abdomens. During this epizootic, five moribund fish showing clear neurological signs were captured and underwent laboratory investigations. Analytical results confirmed the diagnosis of VER in all the specimens. Genetic characterization classified all betanodavirus isolates as belonging to the RGNNV genotype, revealing a close genetic relationship with viral sequences obtained from diseased farmed fish reared in the same area in previous years. The close relationship of the viral sequences between the isolates collected in wild affected fish and those isolated during clinical disease outbreaks in farmed fish in the same area in previous years suggests a persistent circulation of betanodaviruses and transmission between wild and farmed stocks. Further investigations are necessary to assess the risk of viral transmission between wild and farmed fish populations, particularly in marine protected areas where endangered species are present.


Volatile disease biomarkers in breath: a critique.
Hundreds of volatile organic compounds (VOCs) are released from human body fluids. Some of them are produced by endogenous metabolic processes in and on the body, and others are derived from the environment. Expressions of some endogenous VOCs can be affected by pathophysiological changes, and several disease-specific volatile biomarkers have been identified and used as diagnostic aids. Monitoring volatile disease markers is attractive since the procedure can be performed in a noninvasive manner with little or no exposure to biohazardous body fluids. Although many VOCs have been claimed as potential biomarkers, only a few compounds have been consistently demonstrated and approved for clinical applications. This is mainly because (1) many of the putative markers are present in the environment as well as in the body and their levels in the environment are often higher than those in the body, (2) there are a large individual variation in the concentrations of biomarkers within diseased and/or healthy subjects, and (3) the origin and biosynthetic pathway of the claimed biomarkers have been frequently neglected. Unfortunately, these aspects have often been ignored in many studies. Here, we review a number of publications that have identified volatile disease biomarkers in breath, argue that many of these have not demonstrated to actually underlie the differences in volatile profiles between diseased patients and healthy subjects, speculate on the reasons for this lack of success, and suggest potential approaches that may provide a better chance of identifying disease biomarkers.


Vascular expression of glucose transporter in experimental brain neoplasms.
Vascular abnormalities in brain neoplasms are important to tumor biology and therapy. Glucose transporter (GLUT1) expression is a differentiated property of normal cerebral microvessels typically associated with expression of the blood-brain barrier. We investigated the relationship of GLUT1 expression to other vascular characteristics in F98, 9L, and C6 gliomas and Walker 256 carcinomas implanted into adult rat brains. The percentages of microvessels with immunohistochemically detectable GLUT1 were 95.5 +/- 3.9 in F98, 60.9 +/- 3.9 in 9L, 45.4 +/- 5.6 in C6, and 1.2 +/- 0.3 in Walker 256 (mean +/- SEM). The percentage of GLUT1-positive vessels in F98 was not statistically different from that in normal brain. GLUT1 expression was not dependent on restricted permeability as all tumors were highly permeable to Evans blue. GLUT1 expression was unrelated to vascular density, vascular morphology, and parenchymal GFAP expression. The expression of GLUT1, a marker of cerebral endothelial differentiation, is a newly described property of glial tumor vessels that may have diagnostic and prognostic significance.


Mouse allergen exposure and immunologic responses: IgE-mediated mouse sensitization and mouse specific IgG and IgG4 levels.
Although there is evidence that contact with mice is associated with IgE-mediated mouse sensitization and mouse specific antibody responses, the exposure-response relationships remain unclear. To determine whether IgE-mediated mouse sensitization and mouse specific IgG (mIgG) and mIgG4 levels increase with increasing Mus m 1 exposure. One hundred fifty-one workers at a mouse research and production facility were studied. Exposure assignments were made by linking participants to airborne Mus m 1 concentrations in their respective work areas. Cumulative exposure was estimated by multiplying airborne Mus m 1 concentration by duration of employment. Serum mIgG and mIgG4 levels were quantified by antigen-binding assays, and IgE-mediated mouse sensitization was evaluated by skin prick testing (SPT). Prevalence rates of mouse SPT sensitivity and of high levels of mIgG and mIgG4 were increasingly higher by quintiles of increasing cumulative exposure (P < .01 for SPT, mIgG, and mIgG4). After adjusting for age, sex, and atopy, the log odds ratio (OR) of having positive mouse SPT results was linearly related to cumulative exposure (r2 = 0.87), as was the log OR of having a high mIgG level (r2 = 0.86). Quintile of cumulative exposure was an independent predictor of both SPT sensitivity (OR, 1.7; 95% confidence interval, 1.2-2.5) and a high mIgG level (OR, 1.7; 95% confidence interval, 1.2-2.4). IgE-mediated mouse sensitization and mIgG and mIgG4 levels were related to cumulative exposure in a dose-dependent manner. Thus, strategies to prevent allergy to mice should remain focused on reducing mouse allergen exposure.


Phase locking, the Moran effect and distance decay of synchrony: experimental tests in a model system.
Spatially separated populations of many species fluctuate synchronously. Synchrony typically decays with increasing interpopulation distance. Spatial synchrony, and its distance decay, might reflect distance decay of environmental synchrony (the Moran effect), and/or short-distance dispersal. However, short-distance dispersal can synchronize entire metapopulations if within-patch dynamics are cyclic, a phenomenon known as phase locking. We manipulated the presence/absence of short-distance dispersal and spatially decaying environmental synchrony and examined their separate and interactive effects on the synchrony of the protist prey species Tetrahymena pyriformis growing in spatial arrays of patches (laboratory microcosms). The protist predator Euplotes patella consumed Tetrahymena and generated predator-prey cycles. Dispersal increased prey synchrony uniformly over both short and long distances, and did so by entraining the phases of the predator-prey cycles. The Moran effect also increased prey synchrony, but only over short distances where environmental synchrony was strongest, and did so by increasing the synchrony of stochastic fluctuations superimposed on the predator-prey cycle. Our results provide the first experimental demonstration of distance decay of synchrony due to distance decay of the Moran effect. Distance decay of the Moran effect likely explains distance decay of synchrony in many natural systems. Our results also provide an experimental demonstration of long-distance phase locking, and explain why cyclic populations provide many of the most dramatic examples of long-distance spatial synchrony in nature.


Concept of epilepsy surgery and presurgical evaluation.
Epilepsy surgery is a well-accepted treatment for drug-resistant epilepsy. The success of the epilepsy surgery depends upon an appropriate presurgical evaluation process which should ensure the selection of suitable patients who are likely to become seizure-free following surgery without any unacceptable deficit. The two basic goals of the presurgical evaluation are the accurate localization and delineation of the extent of the epileptogenic zone, and its complete and safe resection. The process of the presurgical evaluation requires a multimodality approach wherein each modality provides unique and complimentary information which is combined with the information provided by other modalities to generate a hypothesis with regard to the likely epileptogenic zone. The basic modalities for the presurgical evaluation are clinical history, long-term video-EEG recording, high-resolution MRI, and neuropsychological evaluation. The additional modalities include functional imaging studies, electrical and magnetic source imaging, functional MRI, and intracranial monitoring. Each modality has its own limitations and the information provided by none of them is absolute. Hence, a concordance among the different modalities is the key to surgical success. The presurgical evaluation is a step-wise process starting form the most basic and most reliable tests and progressing to more complex and invasive modalities. The number of tests required varies according to the complexity involved and may include very basic minimum investigations in a given case, to the use of all the available investigations in more complex cases. The proper selection of various investigations and their accurate interpretation at each stage is required to ensure a successful outcome. In this article, we intend to review some of these basic concepts of presurgical evaluation and epilepsy surgery, and try to provide a frame work of the presurgical evaluation process.


Treatment of osteogenesis imperfecta in adults.
Osteogenesis imperfecta (OI) is a heterogeneous rare connective tissue disorder commonly caused by mutations in the collagen type I genes. Pharmacological treatment has been most extensively studied in children, and there are only few studies comprising adult OI patients. i) To review the literature on the current medical management of OI in children and adults, and thereby identify unmet medical needs and ii) to present an overview of possible future treatment options. Individualization and optimization of OI treatment in adults remain a challenge, because available treatments do not target the underlying collagen defect, and available literature gives weak support for treatment decisions for adult patients. Bisphosphonates are still the most widely used pharmacological treatment for adult OI, but the current evidence supporting this is sparse and investigations on indications for choice and duration of treatment are needed.


Roles of state and trait anxiety in physical activity participation for adults with anxiety disorders.
Physical activity has benefits for reducing levels of anxiety. However, factors that affect physical activity participation for individuals with anxiety disorders have not been well studied. Here, we aimed to clarify the roles of state and trait anxiety in physical activity participation by examining relationships among seven major study variables in Taiwanese adults with anxiety disorders. A multi-site, cross-sectional explanatory design was used. Data were collected using one interview and five self-administered questionnaires. The sample included 144 Taiwanese adults diagnosed with anxiety disorders. State and trait anxiety were significantly correlated with most of the study variables. Physical activity participation by subjects with anxiety disorders was significantly correlated with state anxiety, benefits of activity, self-efficacy for activity, and social support for activity. When age, sex, and education were controlled in the analysis, state anxiety was associated significantly and negatively with physical activity, benefits of activity, and self-efficacy for activity, and was correlated positively with barriers to activity. Trait anxiety was found to be correlated significantly and negatively with benefits of activity and self-efficacy for activity, and correlated positively with barriers to activity. State anxiety demonstrated greater power than trait anxiety in its relationship with physical activity. These findings suggest that clinical mental health professionals should consider state anxiety when encouraging Taiwanese adults with anxiety disorders to engage in physical activity.


Evaluating the potential efficacy of three antifungal sealants of duct liner and galvanized steel as used in HVAC systems.
Current recommendations for remediation of fiberglass duct materials contaminated with fungi specify complete removal, which can be extremely expensive, but in-place duct cleaning may not provide adequate protection from regrowth of fungal contamination. Therefore, a common practice in the duct-cleaning industry is the postcleaning use of antifungal surface coatings with the implication that they may contain or limit regrowth. However, even the proper use of these products has generally been discouraged because little research has been conducted on the effectiveness of most products as used in heating, ventilating, and air-conditioning (HVAC) systems. Three different coatings were evaluated on fiberglass duct liner (FGDL). Two of the three coatings were able to limit growth in the 3-month study; the third did not. One of the coatings that was able to limit growth was further evaluated in a comparison of FGDL or galvanized steel (GS) under conditions that mimicked their use in HVAC systems. The results showed that both moderately soiled and heavily soiled uncoated FGDL and GS duct material can support fungal growth, but that GS duct material was more readily cleaned. The use of an antifungal coating helped limit, but did not fully contain, regrowth on FGDL. No regrowth was detected on the coated GS.


Power-law dynamics in an auditory-nerve model can account for neural adaptation to sound-level statistics.
Neurons in the auditory system respond to recent stimulus-level history by adapting their response functions according to the statistics of the stimulus, partially alleviating the so-called "dynamic-range problem." However, the mechanism and source of this adaptation along the auditory pathway remain unknown. Inclusion of power-law dynamics in a phenomenological model of the inner hair cell (IHC)-auditory nerve (AN) synapse successfully explained neural adaptation to sound-level statistics, including the time course of adaptation of the mean firing rate and changes in the dynamic range observed in AN responses. A direct comparison between model responses to a dynamic stimulus and to an "inversely gated" static background suggested that AN dynamic-range adaptation largely results from the adaptation produced by the response history. These results support the hypothesis that the potential mechanism underlying the dynamic-range adaptation observed at the level of the auditory nerve is located peripheral to the spike generation mechanism and central to the IHC receptor potential.


Comparison of Ishihara Booklet with Color Vision Smartphone Applications.
To compare the standard Ishihara booklet with color-vision-testing smartphone applications. A prospective observational diagnostic study on 42 normal trichromats and 38 color-deficient subjects. Patients were presented with three color vision tests in random order: an Ishihara test booklet and two color-vision-testing smartphone applications: Eye2Phone and the Color Vision Test application (CVT app). Sensitivity and specificity of the electronic tests was compared with Ishihara results, and in each one of these applications every plate was individually analyzed for success/failure rate. Average age was 42.7 ± 12.9 years. There were 57 males (71.2%). Sensitivity and specificity of each test was 100% (38/38) and 95.2% (40/42) for the Eye2Phone, and 100% (38/38) and 54.8% (23/42) for the CVT app. There was no significant difference between the Ishihara booklet and the Eye2Phone (p = 0.500), with a high kappa measure of agreement (0.950, p < 0.001). The CVT app was significantly different than both other tests (p < 0.001) with a low kappa measure of agreement (0.535 with the Ishihara and 0.575 with the Eye2Phone). Of the 21 tested plates, color-deficient subjects failed 11.8 ± 3.1 plates in the Ishihara booklet and 14.1 ± 2.1 plates in the Eye2Phone (p < 0.001). Significant plate-specific differences for the color-deficient group were found in plate numbers 3, 6, 7, 8, 9, 15, and 16. Both tests were poorly able to give an indication of the specific dichromatism type. The Ishihara booklet was rated more comfortable and clearer than the Eye2Phone in color-deficient subjects. The CVT app was rated lowest for comfort and clarity in both groups. Smartphone applications testing for color vision deficiency are readily available; however, users of these apps should be aware that some may have different sensitivity for detection of color vision deficiency compared to Ishihara booklet, limiting their usefulness for clinical use. Therefore, further validation of these applications is required.


Differences in intermittent and continuous fecal shedding patterns between natural and experimental Mycobacterium avium subspecies paratuberculosis infections in cattle.
The objective of this paper is to study shedding patterns of cows infected with Mycobacterium avium subsp. paratuberculosis (MAP). While multiple single farm studies of MAP dynamics were reported, there is not large scale meta-analysis of both natural and experimental infections. Large difference in shedding patterns between experimentally and naturally infected cows were observed. Experimental infections are thus probably driven by different pathological mechanisms. For further evaluations of shedding patterns only natural infections were used. Within such infections, the transition to high shedding was studied as a proxy to the development of a clinical disease. The majority of studied cows never developed high shedding levels. Those that do, typically never reduced their shedding level to low or no shedding. Cows that eventually became high shedders showed a pattern of continuous shedding. In contrast, cows with an intermittent shedding pattern had a low probability to ever become high shedders. In addition, cows that start shedding at a younger age (less than three years of age) have a lower hazard of becoming high shedders compared to cows starting to shed at an older age. These data suggest the presence of three categories of immune control. Cows that are intermittent shedders have the infection process under control (no progressive infection). Cows that start shedding persistently at a young age partially control the infection, but eventually will be high shedders (slow progressive infection), while cows that start shedding persistently at an older age cannot effectively control the infection and become high shedders rapidly.