Acculturation and severity of depression among first-generation Vietnamese outpatients in Germany.
Challenges of migration, particularly concerning the process of acculturation are associated with an increased risk of mental illness. Vietnamese migrants constitute the largest Southeast Asian migrant group in Germany, yet there is no data on the relationship between the mental health status and acculturation among this population. Therefore, the present study examines the relationship between two well-established dimensions of acculturation, that is, dominant society immersion (DSI) and ethnic society immersion (ESI), the four resulting acculturation strategies (integration, assimilation, separation and marginalization), and severity of depression. A sample of N = 113 first-generation Vietnamese outpatients from a psychiatric outpatient clinic for Vietnamese migrants in Germany was studied regarding their self-reported depressive symptoms (Beck Depression Inventory-II (BDI-II)) and acculturation (Stephenson Multigroup Acculturation Scale (SMAS)). Consistent with the hypotheses, patients reported less severe depressive symptoms, when they reported higher orientation toward the German and the Vietnamese society. Moreover, the results showed that integrated patients reported a lower severity of depression compared to marginalized patients, who reported the highest severity of depression. The findings indicate that among a sample of first-generation Vietnamese patients with depression, an orientation to both, the mainstream society and one's heritage society might serve as a potential resource. The rejection of any orientation to any society is associated with an increased risk for depression.


An analysis of Snoezelen equipment to reinforce persons with severe or profound mental retardation.
Systematically developing methods of reinforcement for persons with severe and profound mental retardation has only recently received a good deal of attention. This topic is important since professionals in the field often have difficulty identifying sufficient numbers of positive stimuli. Snoezelen equipment as reinforcement for individuals with severe and profound mental retardation was evaluated because of the promise it holds for this population. Types of Snoezelen equipment which were most often approached and most reinforcing for these persons were identified. Implications of the findings for future assessment and treatment are discussed.


The balance model of dyslexia and remedial training: an evaluative study.
The aim of this study was to test the validity of Bakker's (1983, 1990) theory and treatment paradigm of dyslexia. Twenty-one children (mean age = 9.9 years) categorized as P-type dyslexics (showing accurate but slow and fragmented reading) and 19 children (mean age = 9.7 years) categorized as L-type dyslexics (fast but inaccurate readers) were presented with hemisphere-specific stimulation (HSS) and hemisphere-alluding stimulation (HAS). HSS was produced by presenting words to either the left or the right visual half-field, or to the left or right hand of the participant. HAS training was achieved through the presentation of either semantically/phonetically demanding or perceptually demanding text. Participants were given either a treatment program that was specifically designed for their particular dyslexia subtype, or a program that had been deliberately chosen to be inconsistent with their subtype. Contrary to predictions, participants made gains on all of the reading measures, regardless of the type of treatment given. On the basis of these findings it is suggested that treatment gains made are due to nonspecific training effects and not to the specific nature of Bakker's remedial strategies.


The role of computed tomography in the management of children with advanced neuroblastoma.
Computed tomography (CT) was found to be a valuable method of assessing the extent of local disease in 36 patients with advanced neuroblastoma. Precise predictions on the operability of tumours can be made so that the timing of primary or "second look" surgery may be optimised. However, intraspinal extension of tumour is not detected on CT examinations without intrathecal contrast medium and plain radiographs are not a reliable guide to the presence of intraspinal disease; the examination should include intrathecal contrast medium (CT myelography) when patients undergo pre-operative staging by CT. The majority of neuroblastomas appear calcified on CT. During chemotherapy the most common change in tumour morphology is decrease in size and increase in calcification. There is however no correlation between tumour size or behaviour during chemotherapy and eventual survival but an increase in size during or after treatment is a serious prognostic sign.


Obstructive sleep apnea: role of intermittent hypoxia and inflammation.
Obstructive sleep apnea results in intermittent hypoxia via repetitive upper airway obstruction leading to partial or complete upper airway closure, apneas and hypopneas, respectively. Intermittent hypoxia leads to sympathetic nervous system activation and oxidative stress with a resultant systemic inflammatory cascade. The putative mechanism by which obstructive sleep apnea has been linked to numerous pathologic conditions including stoke, cardiovascular disease, hypertension, and metabolic derangements is through these systemic effects. Treatment of obstructive sleep apnea appears to reduce systemic markers of inflammation and ameliorates the adverse sequelae of this disease.


Endoscopic Ultrasound-Guided Treatment beyond Drainage: Hemostasis, Anastomosis, and Others.
Since the introduction of endoscopic ultrasound (EUS) in the 1990s, it has evolved from a primarily diagnostic modality into an instrument that can be used in various therapeutic interventions. EUS-guided fine-needle injection was initially described for celiac plexus neurolysis. By using the fundamentals of this method, drainage techniques emerged for the biliary and pancreatic ducts, fluid collections, and abscesses. More recently, EUS has been used for ablative techniques and injection therapies for patients with for gastrointestinal malignancies. As the search for minimally invasive techniques continued, EUS-guided hemostasis methods have also been described. The technical advances in EUS-guided therapies may appear to be limitless; however, in many instances, these procedures have been described only in small case series. More data are required to determine the efficacy and safety of these techniques, and new accessories will be needed to facilitate their implementation into practice.


Energy storing property of so-called energy-storing prosthetic feet.
The purpose of this study is to evaluate the energy storing and releasing property of 14 different prosthetic feet, in which so-called energy storing prosthetic feet are included. The prostheses were fitted to a young male amputee who walked on a level and slope walkway. Gait-analysis data were obtained by an automatic gait measurement system from which the ankle moment and ankle angular velocity were calculated. From these values, the power and the energy at the ankle joint were calculated. The prosthetic feet were ranked according to the total amount of energy, that is the sum of energy being stored and released. Both of the stored and released energy are important feature of the prosthetic feet. According to these evaluation criteria, we ranked the feet into three groups. The high total energy feet were Flex-Walk,a SAFE II,b and High Functionc. The medium total energy feet were SAFE,b Greissinger,d Seattle,e Copy II,f and Dynamic.d The low total energy feet were Seattle Light,e Fore Joint,g Quantum,h SACH,dSTEN,i and Uniaxial.d As for the subjective feeling, our subject preferred higher energy absorbing feet, in which a somewhat high level of energy was stored but low level of energy was released.


A new hypothesis (concept) of diagnosing Alzheimer's disease.
The diagnosis of dementia has proven problematic due to different criteria. Even neuropathological changes are arbitrarily defined. A mathematical model is proposed that may standardize diagnosis of dementia, and Alzheimer's disease was used as an example. The model suggests that there are cognitive decline curves that represent the rate of natural attrition for neurons in the cerebral cortex. In normal aging, each individual will lose neurons along one curve. Individuals with higher brain reserve will start off at a higher percentile. An accelerated loss of neurons (dementia) is depicted as a deviation from the natural cognitive decline curve. This model may differentiate age-related cognitive decline from dementia or preclinical dementia. Furthermore, it may allow dementia to be diagnosed earlier, hence earlier treatment. Comparison of data may be easier and more valid if the diagnosis of dementia is standardized under this model. Advantages and challenges of this concept are further discussed.


Managing safety signals in large endpoint trials.
We consider the management of safety signals that arise in the context of endpoint trials. Such trials have design features which permit the detection of signals that otherwise may be missed in more traditional settings. However, the approaches that are typically employed to address them are less than satisfactory in terms of both the analytical techniques and the communication of the findings. In this paper, alternative approaches are evaluated, and recommendations are given for a comprehensive strategy that involves appropriate use of study data as well as information external to the study. It is emphasized that formulation and implementation of an effective communication plan that enables informed decision making should be an integral component of the strategy.


The Frequency of CD4+ T Cells in Women with Hashimoto's Thyroiditis.
Hashimoto's thyroiditis (HT) is the most prevalent autoimmune disease, and there is no definitive treatment available for this disease. To find the appropriate therapeutic approach, it is necessary to determine the mechanism of this disease. To achieve this purpose, the frequency of CD4+ T cells was evaluated in patients with HT and compared with healthy individuals. Twenty-six female patients with HT, aged 20 - 45 years, enrolled in this study. Based on the level of thyroglobulin antibody (anti-TG) and anti-thyroid peroxidase antibody (anti-TPO) in serum of patients with HT, they were divided into two groups. The serum level of anti-TPO was above 100 IU/mL in the group 1 (n = 13), whereas the serum levels of both anti-TPO and anti-TG were above 100 IU/mL in the group 2 (n = 13). Eleven healthy women were considered control group, or group 3. Using flow cytometry, the frequency of T helper (Th)1, Th2, Th17, T regulatory type 1 (Tr1), and LT CD4+IL-4+IL-17+ cells and mean fluorescent intensity (MFI) of their related cytokines were evaluated. The frequency of Th2 cells in the groups 1 (anti-TPO > 100) and 2 (anti-TPO > 100 and anti-TG > 100) were more than control group. Only the difference between groups 3 (healthy control) and 2 was significant (P = 0.022). The frequency of LT CD4+IL-4+IL-17+ cells in the group 1 was significantly more than group 3 (P = 0.027); However, the difference between group 2 and 3 was not significant (P = 0.126). The expression of interferon-gamma (IFN-γ) in the group 2 (P = 0.001) and group 1 (P = 0.001) was significantly higher than group 3. The frequency of Th17, Th1, and Tr1 cells and MFI of IL-17 and IL-10 were not significantly different between the study groups. In the present study, no significant differences were observed in the frequency of Th17 and Tr1 cells and in MFI of IL-17 and IL-10 in comparison to healthy individuals. Therefore, trying to make a change in the population of these cells probably does not have a significant therapeutic effect. Since Th2 cells and the expression of IFN-γ increased in women with HT, reducing the frequency of Th2 cells or the expression of IFN-γ may be effective in controlling the disease progression. It may be helpful for these patients to prevent the progression of the disease.


Engineering the protein N-glycosylation pathway in insect cells for production of biantennary, complex N-glycans.
Insect cells, like other eucaryotic cells, modify many of their proteins by N-glycosylation. However, the endogenous insect cell N-glycan processing machinery generally does not produce complex, terminally sialylated N-glycans such as those found in mammalian systems. This difference in the N-glycan processing pathways of insect cells and higher eucaryotes imposes a significant limitation on their use as hosts for baculovirus-mediated recombinant glycoprotein production. To address this problem, we previously isolated two transgenic insect cell lines that have mammalian beta1,4-galactosyltransferase or beta1,4-galactosyltransferase and alpha2,6-sialyltransferase genes. Unlike the parental insect cell line, both transgenic cell lines expressed the mammalian glycosyltransferases and were able to produce terminally galactosylated or sialylated N-glycans. The purpose of the present study was to investigate the structures of the N-glycans produced by these transgenic insect cell lines in further detail. Direct structural analyses revealed that the most extensively processed N-glycans produced by the transgenic insect cell lines were novel, monoantennary structures with elongation of only the alpha1,3 branch. This led to the hypothesis that the transgenic insect cell lines lacked adequate endogenous N-acetylglucosaminyltransferase II activity for biantennary N-glycan production. To test this hypothesis and further extend the N-glycan processing pathway in Sf9 cells, we produced a new transgenic line designed to constitutively express a more complete array of mammalian glycosyltransferases, including N-acetylglucosaminyltransferase II. This new transgenic insect cell line, designated SfSWT-1, has higher levels of five glycosyltransferase activities than the parental cells and supports baculovirus replication at normal levels. In addition, direct structural analyses showed that SfSWT-1 cells could produce biantennary, terminally sialylated N-glycans. Thus, this study provides new insight on the glycobiology of insect cells and describes a new transgenic insect cell line that will be widely useful for the production of more authentic recombinant glycoproteins by baculovirus expression vectors.


Self-compliance at 'Prozac campus'.
This paper focuses on psychiatric medication experiences among a sample of North American university students to explore a new cultural and social landscape of medication 'compliance.' In this landscape, patients assume significant personal decision-making power in terms of dosages, when to discontinue use and even what medications to take. Patients carefully monitor and regulate their moods, and actively gather and circulate newly legitimated blends of expert and experiential knowledge about psychiatric medications among peers, family members and their physicians. The medications too, take a vital role in shaping this landscape, and help to create the spaces for meaning-making and interpretation described and explored in this article. In concluding the article, the authors claim that two popular academic discourses in medical anthropology, one of patient empowerment and shared decision-making and the other of technologies of self and governmentality, may fail to account for other orders of reality that this paper describes - orders shaped and influenced by unconscious, unexpressed and symbolic motivations.


Longer term effect of randomized, controlled group cognitive behavioural therapy for Internet addiction in adolescent students in Shanghai.
The aim of the present study was to evaluate the therapeutic effectiveness of group cognitive behavioural therapy (CBT) for Internet addiction in adolescents. A total of 56 patients, who met Beard's diagnostic criteria for Internet addiction, aged 12-17 years, were divided randomly into an active treatment group (n = 32) and a clinical control group (n = 24). Participants in the active treatment group were treated with an eight-session multimodal school-based group CBT while participants in the clinical control group received no intervention. Internet use, time management, emotional, cognitive and behavioural measures were assessed for both groups at baseline, immediately after the intervention and at 6 month follow up by investigators blind to the participants' group status. Internet use decreased in both groups while only the multimodal school-based group CBT evinced improved time management skills and better emotional, cognitive and behavioural symptoms. Multimodal school-based group CBT is effective for adolescents with Internet addiction, particularly in improving emotional state and regulation ability, behavioural and self-management style.


Kidney dysfunction after non renal solid organ transplantation.
Chronic kidney disease developed after non renal solid organ transplantation in a significant issue. Evaluation of kidney function starting form a complete history and physical examination, then an accurate measurement of renal function and a urinalysis, followed by kidney imaging study should be performed prior to transplantation. Moreover, probability of reversibility of kidney dysfunction and the risk of progression to end stage renal disease should be assessed. During peri- and postoperative period hypotensive episodes should be avoided or at least minimized. Good blood pressure control (however, no guidelines for target blood pressure values for non solid organ transplants are available) as well as tight control of diabetes and hyperlipidemia should be implemented. Proteinuria, if present, should be attenuated by the use of therapeutic modalities (RAS blockade) to prevent or delay the progression of renal failure. The ability to identify CKD may allow early implementation of treatments that could arrest or delay the progression of renal damage, enable effective treatment of its complications, and reduce the risk of drug-induced nephrotoxicity. Kidney function should be monitored in nonrenal solid organ transplant recipients as an important risk factor comparable with diabetes for cardiovascular mortality and morbidity. In presence of existing nephron sparing immunosuppressive regimens, early detection of deteriorating kidney function gives the opportunity to tailor the treatment. A multidisciplinary approach for these patients including also a nephrologist should be considered.


Rapid Stimulation of an Oxidative Burst during Elicitation of Cultured Plant Cells : Role in Defense and Signal Transduction.
Stimulation of cultured plant cells with elicitors of the defense response leads to the rapid destruction of a variety of water-soluble compounds including indoleacetic acid and certain fluorescent dyes. This destructive activity, which is often vigorously manifested within 5 minutes of elicitor addition, is shown to derive from the rapid production of H(2)O(2) and its use by extracellular peroxidases. Because of its speed of appearance, this oxidative burst may qualify as the first induced line of defense against invading pathogens. Since H(2)O(2) has been implicated as a second messenger of hormone-stimulated metabolic changes in some animal cells, its possible role in transduction of the defense signal in plants was also examined. Not only did exogenous H(2)O(2) alone stimulate phytoalexin production in the plant cell suspension, but inhibition of elicitor-stimulated phytoalexin production was observed upon addition of catalase and other inhibitors of the oxidative burst. Furthermore, for inhibition to occur, the presence of catalase was required during elicitor addition, since if introduction of the enzyme was delayed until 1 hour after addition of the elicitor, no inhibition resulted. These results suggest that H(2)O(2) also plays an important role in inducing subsequent defense responses such as phytoalexin production.


Separation of salidroside from Rhodiola crenulata by high-speed counter-current chromatography.
High-speed counter-current chromatography (HSCCC) was used to purify salidroside from an extract of Rhodiola crenulata with two steps using a two-phase solvent system composed of ethyl acetate-n-butanol-water (1:4:5, v/v) in the first run and chloroform-methanol-isopropanol-water (5:6:1:4) in the second run. The method yielded 21.9 mg of salidroside from 1.216 g of the crude sample at 98% purity determined by HPLC analyses. Identification was performed by 1H NMR, 13C NMR, and MS.


Pilot study of mucosal genetic differences in early smokers and nonsmokers.
Global gene expression analysis is proving to be an important means of assessing human tumors and may identify key components of carcinogenesis or clinical prognosis. This technique has been successfully applied to head and neck squamous cell carcinoma (HNSCC) and thyroid carcinomas; however, little has been done to evaluate premalignant states. Human buccal mucosal cells were sampled from smokers and nonsmokers using a noninvasive brush technique. The method was validated by assessing the quantity and quality of RNA obtained. The purified RNA was then assayed using cDNA microarrays containing 27,323 cDNA clones to examine the buccal mucosa in these patients for differences in gene expression patterns. Using unsupervised and supervised hierarchical clustering methods, we developed a gene profile signature for an initial training set of smokers and nonsmokers and then used this to predict smoking status in a subsequent test set of subjects. Selected genes were then cross-referenced with previously published gene sets found in HNSCC identified by our group. Nineteen subjects were used in this pilot analysis, 9 smokers and 10 nonsmokers. Smoking among the study group ranged from 1 to 60 pack years. RNA purified from buccal mucosal brushing demonstrated a high degree of similarity in gene expression profiles among independent samples. Through the application of supervised clustering techniques, we were able to identify 113 genes whose expression differed significantly between samples from smokers and nonsmokers (t test, P < .001). This expression signature was able to accurately predict who within the second set of subjects were smokers, with the exception of one person who had a minimal tobacco history and clustered with the nonsmokers. Cross-referencing data with that found in HNSCC, we were able to identify a tumor suppressor gene involved in the c-myc pathway (Mxi1) that was similarly under-expressed in smokers and cancer patients with progressive disease. Although the sample size was small in this preliminary dataset, our analysis revealed several groups of genes that were either over- or under-expressed in the smokers and which could be used to predict smoking exposure. Many of these represent genes of possible interest as early molecular markers for head and neck carcinogenesis.


Prospects for the development of pre-mortem laboratory diagnostic tests for Creutzfeldt-Jakob disease.
At present the diagnosis of Creutzfeldt-Jakob disease (CJD) and related transmissible spongiform encephalopathies in humans is based on clinical criteria and (at post-mortem) the histopathological and immunological examination of brain tissue. The misfolded prion protein, PrPSc, is the single most significant marker, but its recognition by standard serological methods is complicated by its antigenic similarity to the normal prion protein, PrPC. Although there are commercial diagnostic assays available for bovine spongiform encephalopathy using brain specimens taken at slaughter, there are no suitable pre-mortem assays for cattle and none either for pre-mortem human disease. Especially in view of the recent report of variant CJD transmission by blood transfusion, it is important that tests for pre-symptomatic infections are developed. This will safeguard the blood supply and, for example, prevent the transmission of CJD in neurosurgery. This paper reviews the current and prospective approaches to the pre-mortem diagnosis of CJD, in particular its variant form.


Local neurotoxins for prevention of laryngeal synkinesis after recurrent laryngeal nerve injury.
Persistent vocal fold motion impairment after recurrent laryngeal nerve (RLN) injury is not characteristically due to absent reinnervation, but often results from spontaneous aberrant reinnervation (synkinesis). We administered local neurotoxins to selected laryngeal muscles after RLN injury to determine whether aberrant reinnervation could be selectively inhibited. Unilateral RLN transection was performed in 24 male rats. Three weeks later, the denervated laryngeal adductor complex was injected with phenol, high- or low-dose vincristine sulfate (VNC), or saline solution. One month later, rat larynges were evaluated via videolaryngoscopy and laryngeal electromyography (LEMG). Larynges from euthanized animals were analyzed via immunofluorescent staining for the presence of reinnervation. One animal that received phenol and 3 animals that received high-dose VNC died of toxicity-related complications. In the surviving neurotoxin-treated animals, videolaryngoscopy showed increased lateralization of the immobile vocal fold. Only 1 phenol-injected rat had adductor complex motor recruitment (score of 3+) with LEMG. The other neurotoxin-treated animals demonstrated an absence of adductor complex reinnervation, with only insertional activity and fibrillations (no motor units/recruitment). Spontaneous ipsilateral abductor reinnervation was not affected by the adductor injections. Low-dose VNC injections appear to be relatively safe and effective in selectively inhibiting spontaneous aberrant reinnervation after RLN injury in an animal model.


In situ study of the antibacterial activity and mechanism of action of silver nanoparticles by surface-enhanced Raman spectroscopy.
Silver nanoparticles (Ag NPs) are extensively used as an antibacterial additive in commercial products and their release has caused environmental risk. However, conventional methods for the toxicity detection of Ag NPs are very time consuming and the mechanisms of action are not clear. We developed a new, in situ, rapid, and sensitive fingerprinting approach, using surface-enhanced Raman spectroscopy (SERS), to study the antibacterial activity and mechanism of Ag NPs of 80 and 18 nm (Ag80 and Ag18, respectively), by using the strong electromagnetic enhancement generated by Ag NPs. Sensitive spectra changes representing various biomolecules in bacteria were observed with increasing concentrations of Ag NPs. They not only allowed SERS to monitor the antibacterial activity of Ag NPs of different sizes in different water media but also to study the antibacterial mechanism at the molecular level. Ag18 were found to be more toxic than Ag80 in water, but their toxicity declined to a similar level in the PBS medium. The antibacterial mechanism was proposed on the basis of a careful identification of the chemical origins by comparing the SERS spectra with model compounds. The dramatic change in protein, hypoxanthine, adenosine, and guanosine bands suggested that Ag NPs have a significant impact on the protein and metabolic processes of purine. Finally, by adding nontoxic and SERS active Au NPs, SERS was successfully utilized to study the action mode of the NPs unable to produce an observable SERS signal. This work opens a window for the future extensive SERS studies of the antibacterial mechanism of a great variety of non-SERS-active NPs.


The dormant epicardial reconnection of pulmonary vein: an unusual cause of recurrent atrial fibrillation after pulmonary vein isolation.
The case of a 65-year-old man with recurrent atrial fibrillation after undergoing segmental pulmonary vein isolation caused by the reconnection of previously isolated pulmonary veins is herein reported. Interestingly, frequent ectopic firings in the left superior pulmonary vein conducted to the left atrium, not through its ostium but through the supposed epicardial pathway at the region of the Marshall ligament, which had been absent during the first treatment session. The reisolation of the left superior pulmonary vein by radiofrequency application in the left atrial appendage thus successfully eliminated the occurrence of atrial fibrillation.


Membrane trafficking RNA interference screen identifies a crucial role of the clathrin endocytic pathway and ARP2/3 complex for Japanese encephalitis virus infection in HeLa cells.
Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is one of the leading global causes of virus-induced encephalitis. The infectious life-cycle of viruses is heavily dependent on the host membrane trafficking network. Here, we have performed a RNA-interference-based screen using a siRNA panel targeting 136 membrane trafficking proteins to identify the key regulators of JEV infection in HeLa cells. We identified 35 proteins whose siRNA depletion restricts JEV replication by over twofold. We observe that JEV infection in HeLa cells is largely dependent on components of the clathrin-mediated endocytic (CME) pathway. Proteins involved in actin-filament-based processes, specifically CDC42 and members of the ARP2/3 complex are crucial for establishment of infection. Pharmacological pertubations of actin polymerization, a small molecule inhibitor of actin nucleation by the ARP2/3 complex - CK-548 - and the inhibitor of neural Wiskott-Aldrich syndrome proteins- Wiskostatin- inhibited JEV replication, highlighting the important role of the dynamic actin network. Other proteins involved in cargo-recognition for CME and endomembrane system organization were also validated as essential host factors for virus replication.


Transcription strategy in a Closterovirus: a novel 5'-proximal controller element of Citrus Tristeza Virus produces 5'- and 3'-terminal subgenomic RNAs and differs from 3' open reading frame controller elements.
Citrus tristeza virus (CTV) produces more than thirty 3'- or 5'-terminal subgenomic RNAs (sgRNAs) that accumulate to various extents during replication in protoplasts and plants. Among the most unusual species are two abundant populations of small 5'-terminal sgRNAs of approximately 800 nucleotides (nt) termed low-molecular-weight tristeza (LMT1 and LMT2) RNAs. Remarkably, CTV replicons with all 10 3' genes deleted produce only the larger LMT1 RNAs. These 5'-terminal positive-sense sgRNAs do not have corresponding negative strands and were hypothesized to be produced by premature termination during plus-strand genomic RNA synthesis. We characterized a cis-acting element that controls the production of the LMT1 RNAs. Since manipulation of this cis-acting element in its native position (the L-ProI region of replicase) was not possible because the mutations negatively affect replication, a region (5'TR) surrounding the putative termination sites (nt approximately 550 to 1000) was duplicated in the 3' end of a CTV replicon to allow characterization. The duplicated sequence continued to produce a 5'-terminal plus-strand sgRNA, here much larger ( approximately 11 kb), apparently by termination. Surprisingly, a new 3'-terminal sgRNA was observed from the duplicated 5'TR. A large 3'-terminal sgRNA resulting from the putative promoter activity of the native 5'TR was not observed, possibly because of the down-regulation of a promoter approximately 19 kb from the 3' terminus. However, we were able to observe a sgRNA produced from the native 5'TR of a small defective RNA, which placed the native 5'TR closer to the 3' terminus, demonstrating sgRNA promoter activity of the native 5'TR. Deletion mutagenesis mapped the promoter and the terminator activities of the 5'TR (in the 3' position in the CTV replicon) to a 57-nt region, which was folded by the MFOLD computer program into two stem-loops. Mutations in the putative stem-loop structures equally reduced or prevented production of both the 3'- and 5'-terminal sgRNAs. These mutations, when introduced in frame in the native 5'TR, similarly abolished the synthesis of the LMT1 RNAs and presumably the large 3'-terminal sgRNA while having no impact on replication, demonstrating that neither 5'- nor 3'-terminal sgRNA is necessary for replication of the replicon or full-length CTV in protoplasts. Differences between the 5'TR, which produced two plus-strand sgRNAs, and the cis-acting elements controlling the 3' open reading frames, which produced additional minus-strand sgRNAs corresponding to the 3'-terminal mRNAs, suggest that the different sgRNA controller elements had different origins in the modular evolution of closteroviruses.


Control of early postoperative pain with bupivacaine in pediatric tonsillectomy.
Early postoperative pain following pediatric tonsillectomy remains a significant obstacle to speedy recovery and smooth convalescence. Inadequate analgesia causes poor oral intake and occasionally requires overnight hospitalization in same day surgery practices. Several otolaryngologists anecdotally support intraoperative infiltration with a long-acting amide anesthetic, bupivacaine hydrochloride, for postoperative pain control. However, no previous study supports these claims. At the National Naval Medical Center, a prospective, randomized, double-blinded study was undertaken in fifty patients, ages 3 to 16 years old. After tonsil resection, either 0.5% bupivacaine or saline was injected into each fossa. We asked the parents three questions. First, what was the level of pain at 2, 6 and 10 hours postoperatively? Second, what was the amount of oral intake during the first 10 hours after surgery? And third, how many doses of oral acetaminophen elixir were administered over the first 10 postoperative hours? Bupivacaine administration caused no adverse effects. There was no difference in perceived pain level between bupivacaine and saline groups at 2, 6 and 10 hours. Oral intake levels over the first 10 hours were similar. Although bupivacaine group patients received fewer doses of oral acetaminophen, the difference between groups was not statistically significant. We conclude that bupivacaine is a safe medication for infiltration, but offers no advantage over saline in the control of early postoperative pain in pediatric tonsillectomy.


Emerging cellular and immunotherapies for systemic sclerosis: from mesenchymal stromal cells to CAR-T cells and vaccine-based approaches.
Although two targeted therapies have received recent approval for systemic sclerosis (SSc)-associated interstitial lung disease, they do not show major disease-modifying activity, highlighting the need for novel therapies and innovative paradigms. To that end, cellular therapies may represent a new opportunity for the treatment of SSc. The purpose of this review is to provide an up-to-date overview of emerging cell-based disease-modifying therapies in SSc. Initial small studies in patients with severe refractory systemic lupus erythematosus (SLE) using engineered regulatory cells show promising results. CD19-directed CAR-T have shown promising results in one case report of refractory diffuse cutaneous SSc patients. T cells engineered to express a chimeric autoantibody receptor (CAAR-T cells) may be even more relevant via the specific elimination of auto-reactive B cells. Targeting pro-fibrotic or senescence-related pathways may also constitute promising approaches in SSc. Building on the classification of the clinical phenotype and prediction of clinical trajectory based on individual patients' autoantigen and/or autoantibody profile, cellular therapies targeting the same autoantigen or related autoreactive cells may represent an unprecedented opportunity to implement personalized medicine in SSc.


Cognitive preservation following awake mapping-based neurosurgery for low-grade gliomas: A longitudinal, within-patient design study.
Awake surgery with intraoperative electrical mapping emerged as a gold-standard approach in newly diagnosed diffuse low-grade glioma (DLGG) to optimize the extent of resection (EOR) while sparing critical brain structures. However, no study has assessed to what extent cognitive recovery occurs following awake mapping-guided neurosurgery in a large, longitudinal, and homogeneous series of DLGG. A longitudinal study on the cognitive status of 157 DLGG patients was performed. Neuropsychological assessments were done before and three months after awake mapping-based surgery. Z-scores and variations of Z-scores were computed to determine the number of patients with cognitive deficit(s) or decline. Clinical, surgical, and histopathological variables were studied to investigate factors contributing to neurocognitive outcomes. Eighty-seven patients (55.4%) had preoperative cognitive impairments. Statistical analysis between the preoperative (baseline) and postoperative assessments demonstrated a significant difference in three domains (Executive, Psychomotor Speed and Attention, Verbal Episodic Memory). Eighty-six percent of patients exhibited no postoperative cognitive decline, and among them, 10% exhibited cognitive improvement. The mean EOR was 92.3%±7.8%. The EOR, postoperative volume, and tumor lateralization had a significant association with cognitive decline. No patients demonstrated permanent postoperative neurologic deficits, but 5.8% did not resume their preoperative professional activities. The 5-year survival rate was 82.2%. This is the largest series ever reported with systematic longitudinal neuropsychological assessment. 86% of patients demonstrated no cognitive decline despite large resections and only 5.8% did not return to work. This work supports the practice of awake surgery with cognitive mapping as safe and effective in DLGG patients.


Gene expression analysis of host innate immune responses during Lethal H5N1 infection in ferrets.
How viral and host factors contribute to the severe pathogenicity of the H5N1 subtype of avian influenza virus infection in humans is poorly understood. We identified three clusters of differentially expressed innate immune response genes in lungs from H5N1 (A/Vietnam/1203/04) influenza virus-infected ferrets by oligonucleotide microarray analysis. Interferon response genes were more strongly expressed in H5N1-infected ferret lungs than in lungs from ferrets infected with the less pathogenic H3N2 subtype. In particular, robust CXCL10 gene expression in H5N1-infected ferrets led us to test the pathogenic role of signaling via CXCL10's cognate receptor, CXCR3, during H5N1 influenza virus infection. Treatment of H5N1-infected ferrets with the drug AMG487, a CXCR3 antagonist, resulted in a reduction of symptom severity and delayed mortality compared to vehicle treatment. We contend that unregulated host interferon responses are at least partially responsible for the severity of H5N1 infection and provide evidence that attenuating the CXCR3 signaling pathway improves the clinical course of H5N1 infection in ferrets.


Activation of high and low affinity dopamine receptors generates a closed loop that maintains a conductance ratio and its activity correlate.
Neuromodulators alter network output and have the potential to destabilize a circuit. The mechanisms maintaining stability in the face of neuromodulation are not well described. Using the pyloric network in the crustacean stomatogastric nervous system, we show that dopamine (DA) does not simply alter circuit output, but activates a closed loop in which DA-induced alterations in circuit output consequently drive a change in an ionic conductance to preserve a conductance ratio and its activity correlate. DA acted at low affinity type 1 receptors (D1Rs) to induce an immediate modulatory decrease in the transient potassium current (IA) of a pyloric neuron. This, in turn, advanced the activity phase of that component neuron, which disrupted its network function and thereby destabilized the circuit. DA simultaneously acted at high affinity D1Rs on the same neuron to confer activity-dependence upon the hyperpolarization activated current (Ih) such that the DA-induced changes in activity subsequently reduced Ih. This DA-enabled, activity-dependent, intrinsic plasticity exactly compensated for the modulatory decrease in IA to restore the IA:Ih ratio and neuronal activity phase, thereby closing an open loop created by the modulator. Activation of closed loops to preserve conductance ratios may represent a fundamental operating principle neuromodulatory systems use to ensure stability in their target networks.


Cutaneous xanthogranulomas, hepatosplenomegaly, anemia, and thrombocytopenia as presenting signs of juvenile myelomonocytic leukemia.
The development of xanthogranulomas has been linked to hematologic malignancies in children and adults, based on a number of reports in the literature. In children, a specific association between juvenile xanthogranuloma, neurofibromatosis 1, and juvenile myelomonocytic leukemia has been described. We report a case of a 9-month-old child, without a known diagnosis of neurofibromatosis 1, who presented with hepatosplenomegaly, anemia, thrombocytopenia, and multiple cutaneous nodules, which were confirmed to be juvenile xanthogranulomas upon biopsy. A concurrent work-up showed that the child had juvenile myelomonocytic leukemia. Although cutaneous juvenile xanthogranulomas are benign lesions, in several reported cases they have been shown to herald leukemia. This association between xanthogranulomas and hematologic malignancy is poorly understood. Juvenile xanthogranulomas have a number of morphologic variants and clinical presentations that can be confused with the cutaneous lesions of Langerhans cell histiocytosis and dermatofibroma. Recognition of the broad clinicopathologic spectrum of juvenile xanthogranulomas is critical for proper diagnosis.


Light in the built environment: potential role of circadian disruption in endocrine disruption and breast cancer.
Life in industrialized societies is primarily life inside buildings. Illumination from electric lighting in the built environment is quite different from solar radiation in intensity, spectral content, and timing during the 24-hour daily period. Humans evolved over millions of years with the day-night pattern of solar radiation as the primary circadian cue. This pattern maintained a 24-hour rhythm of melatonin release, as well as a host of other physiological rhythms including the sleep-wake cycle. Electric lighting in the built environment is generally more than sufficient for visual performance, but may be inappropriate for the maintenance of normal neuroendocrine rhythms in humans; e.g., insufficient during the day and too much at night. Lighting standards and engineering stress visual performance, whereas circadian function is not currently emphasized. The molecular biological research on the circadian clock and on mechanisms of phototransduction makes it clear that light for vision and light for circadian function are not identical systems. In particular, if electric lighting as currently employed contributes to 'circadian disruption' it may be an important cause of 'endocrine disruption' and thereby contribute to a high risk of breast cancer in industrialized societies.


Subcutaneous tissue thickness is an independent predictor of image noise in cardiac CT.
Few data on the definition of simple robust parameters to predict image noise in cardiac computed tomography (CT) exist. To evaluate the value of a simple measure of subcutaneous tissue as a predictor of image noise in cardiac CT. 86 patients underwent prospective ECG-gated coronary computed tomographic angiography (CTA) and coronary calcium scoring (CAC) with 120 kV and 150 mA. The image quality was objectively measured by the image noise in the aorta in the cardiac CTA, and low noise was defined as noise < 30 HU. The chest anteroposterior diameter and lateral width, the image noise in the aorta and the skin-sternum (SS) thickness were measured as predictors of cardiac CTA noise. The association of the predictors and image noise was performed by using Pearson correlation. The mean radiation dose was 3.5 ± 1.5 mSv. The mean image noise in CT was 36.3 ± 8.5 HU, and the mean image noise in non-contrast scan was 17.7 ± 4.4 HU. All predictors were independently associated with cardiac CTA noise. The best predictors were SS thickness, with a correlation of 0.70 (p < 0.001), and noise in the non-contrast images, with a correlation of 0.73 (p < 0.001). When evaluating the ability to predict low image noise, the areas under the ROC curve for the non-contrast noise and for the SS thickness were 0.837 and 0.864, respectively. Both SS thickness and CAC noise are simple accurate predictors of cardiac CTA image noise. Those parameters can be incorporated in standard CT protocols to adequately adjust radiation exposure.


Horizontal condylar angle in relation to internal derangement of the temporomandibular joint.
The angle between the horizontal condylar long axis and the frontal plane was measured and correlated with arthrographic diagnosis in 364 consecutive temporomandibular joint patients. There were no statistically significant associations between the horizontal condylar angle and the arthrographic diagnosis. The condylar angle of the contralateral joint however, was, found to be larger in patients with unilateral anterior disk displacement than in patients with normal temporomandibular joints. There is no immediate explanation of this finding, but it supports previous observations and may contribute to the understanding of the etiology and the pathogenesis of internal derangement of the temporomandibular joint.


"Learning is about being active, but the digital is not really active": physiotherapy teachers' attitudes toward and experiences with digital education.
Digital education is expected to transform higher education teaching and learning. Despite high expectations, higher education teachers have been slow to implement active digital learning. The aim of this study was to investigate physiotherapy teachers' attitudes toward and experiences with digital education and what the teachers' considered prerequisites to a digital transformation of teaching and learning in physiotherapy. Qualitative in-depth interviews were conducted with 12 teachers in physiotherapy education. The interviews were analyzed using inductive thematic analysis. The findings illuminate teachers' attitudes toward and experiences with digital education and their views on prerequisites to a digital transformation of teaching and learning in physiotherapy education, presented as four themes: 1) skepticism toward digital education; 2) digital technology as a tool to support the established teaching practice; 3) longing for teacher collaboration; and 4) calling for time to plan and learn, and significant academic leadership. This study shows how physiotherapy teachers are skeptical about digital education, primarily viewing it as a threat to established teaching practices. Taken together, the findings demonstrate a potential for digital transformation in physiotherapy education, which can be released by informing the current teaching practices with evidence from research showing how use of digital technology can improve teaching and learning in physiotherapy education.


[The combination effects of antibacterial agents against clinical isolated multiple-drug resistant Pseudomonas aeruginosa].
The effectiveness of antibacterial agents against 70 strains of clinically isolated multiple-drug resistant Pseudomonas aeruginosa (MDRP) was measured by the micro dilution method. Fifty of all strains (71%) produced metallo-beta-lactamase and the IMP-1 gene was detected by polymerase chain reaction (PCR). The MIC90 (the minimum inhibitory concentration of an antibiotic necessary to inhibit the growth of 90% of bacterial strains) values of biapenem (BIPM), meropenem (MEPM), tazobactam/piperacillin (TAZ/PIPC), sulbactam/ cefoperazone (SBT/CPZ), cefepime (CFPM), ciprofloxacin (CPFX), pazufloxacin (PZFX), amikacin (AMK) and aztreonam (AZT) were found to be 265, 512, 256, 512, 512, 64, 128, 128 and 128 microg/mL, respectively. The in vitro combination effects of antibacterial agents were examined against 62 strains of MDRP and the synergy or additive effects were evaluated by fractional inhibitory concentration (FIC) index calculated by the checkerboard method. The combination of AMK and AZT showed synergy effects on 15/59 (25.4%) strains of MDRP. The synergy and additive effects on the MDRP strains were also found by the other antibacterial agents combination such as TAZ/PIPC and AMK, CFPM and AMK, and SBT/CPZ and AZT. These results suggested the necessity of further investigation of clinical usefulness.


Mathematical Modeling for the Industrial 2-Mercaptobenzothiazole Batch Production Process.
As an important chemical intermediate, 2-mercaptobenzothiazole (MBT) is widely used in various processes, especially in the rubber industry. However, there is no first-principles model that describes the synthetic process of MBT. This paper focuses on the formulation of a reliable mathematical model represented by a series of differential and algebraic equations for the industrial batch MBT production process. It is difficult to estimate all of the unknown parameters in the model because of the lack of sufficient industrial/experimental data. Thus, a reduced estimable parameter set is derived by performing estimability analysis on the original estimation problem. A multiple-starting-point strategy is then applied to numerically solve the non-convex parameter estimation problem with the weighted least-squares approach. Subsequently, a cross-validation technique is employed to evaluate the generalizability of the proposed model. Finally, it is confirmed that the proposed model produces encouraging prediction performance with regard to independent test data.


Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase.
A group of phosphoinositide 3-kinase (PI3K) inhibitors, such as 3-methyladenine (3-MA) and wortmannin, have been widely used as autophagy inhibitors based on their inhibitory effect on class III PI3K activity, which is known to be essential for induction of autophagy. In this study, we systematically examined and compared the effects of these two inhibitors on autophagy under both nutrient-rich and deprivation conditions. To our surprise, 3-MA is found to promote autophagy flux when treated under nutrient-rich conditions with a prolonged period of treatment, whereas it is still capable of suppressing starvation-induced autophagy. We first observed that there are marked increases of the autophagic markers in cells treated with 3-MA in full medium for a prolonged period of time (up to 9 h). Second, we provide convincing evidence that the increase of autophagic markers is the result of enhanced autophagic flux, not due to suppression of maturation of autophagosomes or lysosomal function. More importantly, we found that the autophagy promotion activity of 3-MA is due to its differential temporal effects on class I and class III PI3K; 3-MA blocks class I PI3K persistently, whereas its suppressive effect on class III PI3K is transient. Because 3-MA has been widely used as an autophagy inhibitor in the literature, understanding the dual role of 3-MA in autophagy thus suggests that caution should be exercised in the application of 3-MA in autophagy study.


Spring fasting behavior in a marine apex predator provides an index of ecosystem productivity.
The effects of declining Arctic sea ice on local ecosystem productivity are not well understood but have been shown to vary inter-specifically, spatially, and temporally. Because marine mammals occupy upper trophic levels in Arctic food webs, they may be useful indicators for understanding variation in ecosystem productivity. Polar bears (Ursus maritimus) are apex predators that primarily consume benthic and pelagic-feeding ice-associated seals. As such, their productivity integrates sea ice conditions and the ecosystem supporting them. Declining sea ice availability has been linked to negative population effects for polar bears but does not fully explain observed population changes. We examined relationships between spring foraging success of polar bears and sea ice conditions, prey productivity, and general patterns of ecosystem productivity in the Beaufort and Chukchi Seas (CSs). Fasting status (≥7 days) was estimated using serum urea and creatinine levels of 1,448 samples collected from 1,177 adult and subadult bears across three subpopulations. Fasting increased in the Beaufort Sea between 1983-1999 and 2000-2016 and was related to an index of ringed seal body condition. This change was concurrent with declines in body condition of polar bears and observed changes in the diet, condition and/or reproduction of four other vertebrate consumers within the food chain. In contrast, fasting declined in CS polar bears between periods and was less common than in the two Beaufort Sea subpopulations consistent with studies demonstrating higher primary productivity and maintenance or improved body condition in polar bears, ringed seals, and bearded seals despite recent sea ice loss in this region. Consistency between regional and temporal variation in spring polar bear fasting and food web productivity suggests that polar bears may be a useful indicator species. Furthermore, our results suggest that spatial and temporal ecological variation is important in affecting upper trophic-level productivity in these marine ecosystems.


Thermotactile thresholds at the fingertip: effect of contact area and contact location.
Thresholds for the detection of changes in temperature are used to indicate neuropathy, but a variety of different contact areas and contact locations are used. This study was designed to determine the effects of variations in contact area and contact location on both warm and cool thresholds at the fingertip. With 20 healthy subjects (10 females and 10 males aged 20-30 years), warm thresholds and cool thresholds were determined in two separate sessions using the method of limits. In the first part of each session, thresholds were determined around the centre of the whorl using circular contactors with five different diameters (3, 6, 9, 12, and 55 mm). In the second part of each session, thresholds were determined using two contactors (6- and 12-mm diameter) at three locations along the fingertip: (i) distal (5 mm from the nail), (ii) middle (centre of whorl), and (iii) proximal (3 mm from the distal interphalangeal joint). With increasing contact area, the warm thresholds decreased, the cool thresholds increased, and the inter-subject variability in both warm and cool thresholds decreased. Using the 6-mm diameter contactor, warm thresholds were independent of location but cool thresholds increased from distal to proximal locations. It is concluded that temperature sensitivity at the fingertip increases with increasing area of contact, with the variability in thresholds consistent with the existence of warm and cool "insensitive fields". The findings show that the influence of contact area and contact location should be considered when assessing thermotactile thresholds at the fingertip.


Molecular characterization of LH-beta and FSH-beta subunits and their regulation by estrogen in the goldfish pituitary.
The gonadal steroids, along with gonadotropin-releasing hormone (GnRH) are involved in the regulation of gonadotropin (GtH) production in vertebrates. Goldfish have an annual reproductive cycle, characterized by seasonal fluctuations in the circulating levels of the reproductive hormones, including 17beta-estradiol (E2). The purpose of the present study was to investigate the effect of E2 on basal and GnRH-induced GtH subunit (alpha, FSH-beta and LH-beta) gene expression in the goldfish pituitary. Northern analyses were performed to determine changes in steady state mRNA levels. Both in vivo and in vitro treatment with E2 resulted in a stimulation of all three GtH subunit mRNA levels, although a higher concentration was required for the stimulation of the FSH-beta subunit mRNA levels. The effect of E2 on GnRH-induced GtH mRNA level was also investigated and demonstrated that E2 influences the GnRH-induced GtH subunit mRNA levels in a seasonally dependent manner. Overall, the present results indicate that E2 stimulates GtH subunit mRNA levels directly at the level of the pituitary in a seasonally dependent manner in goldfish.


Extinction of self-injurious escape behavior with and without instructional fading.
Three individuals with developmental disabilities participated in a study of the treatment of self-injurious behavior (SIB) maintained by negative reinforcement (escape from educational tasks). Treatment was implemented in a multiple baseline design across subjects, in which two treatments were compared in a multielement format. Both treatment conditions included an escape-extinction component in which SIB no longer produced escape. One of the conditions also included a fading component in which the frequency of instructions was initially reduced to zero and then was gradually faded back in across sessions until the instructional rate matched that of the original baseline. Results indicated that extinction alone reduced SIB to the end-of-treatment criterion in fewer sessions than did extinction plus fading for all 3 subjects. For 2 of the 3 subjects, however, there was an initial increase in the frequency of SIB at the outset of treatment with extinction (an extinction burst) that was not observed when extinction was combined with the fading component.


ALS-linked Cu/Zn-SOD mutation impairs cerebral synaptic glucose and glutamate transport and exacerbates ischemic brain injury.
Although degeneration of lower motor neurons is the most striking abnormality in amyotrophic lateral sclerosis (ALS), more subtle alterations may occur in the brain. Mutations in copper/zinc superoxide dismutase (Cu/Zn-SOD) are responsible for some cases of inherited ALS, and expression of mutant Cu/Zn-SOD in transgenic mice results in progressive motor neuron loss and a clinical phenotype similar to that of ALS patients. It is now reported that Cu/Zn-SOD mutant mice exhibit increased vulnerability to focal ischemic brain injury after transient occlusion of the middle cerebral artery. Levels of glucose and glutamate transport in cerebral cortex synaptic terminals were markedly decreased, and levels of membrane lipid peroxidation were increased in Cu/Zn-SOD mutant mice compared to nontransgenic mice. These findings demonstrate that mutant Cu/Zn-SOD may endanger brain neurons by a mechanism involving impairment of glucose and glutamate transporters. Moreover, our data demonstrate a direct adverse effect of the mutant enzyme on synaptic function.


hCAR-EGFP fusion receptor in human follicular lymphoma B cells - a model for adenoviral gene therapy for B cell malignancies.
Adenovirus-mediated gene therapy for hematopoietic malignancies, especially those derived from B cells, is difficult due to systemic nature of these diseases. More importantly, most tumor cells derived from B cell lineage express a very low level of the adenovirus receptor hCAR; thus, warranting the design of adenoviral vectors with high affinity to abundant B cell surface molecules. To mimic this approach and to test the validity of adenoviral vectors in gene therapy of disseminated malignancies, we created an hCAR-expressing follicular lymphoma B cell line. The cell line was generated with the aid of a lentivirus vector carrying a novel fusion gene with EGFP replacing the cytoplasmic domain of hCAR. After verifying that this cell line was expressing the hybrid receptor in a correct manner and enrichment of the bright EGFP positive population, the cells were transduced with adenoviruses expressing the red fluorescent protein DsRed2. It was shown that regular transduction with a low viral dose (1 pfu/cell) increased the gene transfer rate by a factor of 5. Furthermore, experiments with adenovirus vector carrying the HSV-TK-GFP transgene demonstrated that the modified follicular lymphoma B cells became sensitive to ganciclovir while the parental cells remained virtually resistant to this form of gene therapy. In summary, we show here with this simple model system that adenoviral gene therapy of B cell malignancies is possible provided that correct receptors for adenovirus attachment are present on the surface of the target cells. Thus, our results warrant further modifications of adenovirus capsid to obtain vectors with specific affinity to B cell epitopes.


Interactive effects of dietary ractopamine HCl and L-carnitine on finishing pigs: I. Growth performance.
A total of 2,152 pigs (C22 × 336 PIC) were used in 4 experiments to determine the interactive effects of dietary l-carnitine and ractopamine HCl (RAC) on finishing pig growth performance. All trials were arranged as factorial arrangements with main effects of l-carnitine (0, 25, or 50 mg/kg in Exp. 1 and 2 and 0 or 50 mg/kg in Exp. 3 and 4) and RAC (0, 5, or 10 mg/kg in Exp. 1 and 0 or 10 mg/kg in Exp. 2, 3, and 4). Dietary carnitine was fed from 38 to 109 kg (Exp. 1 and 3) or for the last 4 or 3 wk before slaughter (118 kg; Exp. 2 and 4, respectively). Ractopamine HCl was fed for 4 wk (Exp. 1, 2, and 3) or 3 wk (Exp. 4) before slaughter. Experiments 1 and 2 were conducted in university research facilities, and Exp. 3 and 4 were conducted in a commercial research facility. All diets were formulated to contain 1.00% total Lys during the last phase of each experiment. In all experiments, pigs fed RAC had increased (P < 0.05) ADG and G:F compared with pigs fed no RAC. Feeding l-carnitine before the RAC feeding period did not affect pig growth performance. In Exp. 1 and 2, l-carnitine did not affect ADG during the last 4 wk; however, in Exp. 2, G:F tended (quadratic; P = 0.07) to improve with increasing l-carnitine. In Exp. 3, l-carnitine × RAC interactions were observed (P < 0.04) for ADG and G:F. Both added l-carnitine and RAC improved performance, but the response was not additive. In Exp. 4, pigs fed l-carnitine had increased (P < 0.04) ADG (0.88 vs. 0.84 kg) and G:F (0.36 vs. 0.35) compared with pigs fed no l-carnitine, and the response was additive to that of RAC. Analysis of treatments common to all experiments showed that pigs fed RAC had increased (P < 0.01) ADG (1.03 vs. 0.93 kg) and G:F (0.40 vs. 0.35) compared with pigs fed no RAC. Pigs fed l-carnitine tended to have increased (P = 0.07) ADG (1.00 vs. 0.96 kg) and improved (P < 0.01) G:F (0.38 vs. 0.37) compared with pigs not fed l-carnitine. These results confirm that RAC improves growth performance of finishing pigs. Added l-carnitine improved growth performance of finishing pigs, and the greatest response was observed in Exp. 3 and 4, which were conducted in commercial research environments. These experiments imply that adding l-carnitine to a finishing diet does not enhance the growth effects of RAC and that effects of RAC and l-carnitine on ADG and G:F are independent.


Multicenter evaluation of the Acaruiter Respiratory Panel for diagnosis of respiratory tract infections in Chinese children.
Compared to multiplex PCR assays that are available in the Chinese market, the Acaruiter Respiratory Panel (fluorescent PCR) covers a wider range of pathogens including eight viruses, five bacteria, Mycoplasma pneumoniae and Chlamydia pneumoniae, and has high accuracy and effectiveness in the detection of pathogens. This is the first study to evaluate the performance of the Acaruiter Respiratory Panel. This regent may be a promising assay for comprehensive testing for respiratory pathogens from nasopharyngeal swab specimens in Chinese children.


Clinical and Radiographic Outcomes of a Posteriorly Augmented Glenoid Component in Anatomic Total Shoulder Arthroplasty for Primary Osteoarthritis with Posterior Glenoid Bone Loss.
The primary objectives of this study were to evaluate the ability of a posteriorly stepped augmented glenoid component, used in patients with primary glenohumeral osteoarthritis with B2 or B3 glenoid morphology, to correct preoperative retroversion and humeral head subluxation and to identify factors associated with radiographic radiolucency and patient-reported clinical outcomes. We identified 71 shoulders with B2 or B3 glenoid morphology that underwent anatomic total shoulder arthroplasty with use of a posteriorly stepped augmented glenoid component and with a preoperative 3-dimensional computed tomography (3D-CT) scan and a minimum of 2 years of clinical and radiographic follow-up. The Penn Shoulder Score (PSS), shoulder range of motion, glenoid center-peg osteolysis, and postoperative version and humeral head subluxation were the main outcome variables of interest. Follow-up was a median of 2.4 years (range, 1.9 to 5.7 years); the mean patient age at treatment was 65 ± 7 years (range, 51 to 80 years). PSS, range of motion, humeral head centering, and glenoid version were significantly improved among all patients (p < 0.0001). Patients with persistent posterior subluxation of the humeral head postoperatively had worse preoperative fatty infiltration of the teres minor and greater postoperative component retroversion (p < 0.05). Patients with center-peg osteolysis had more preoperative joint-line medialization and posterior glenoid bone loss (p < 0.05). Patients with more preoperative humeral head posterior subluxation had a lower PSS, adjusting for confounders (p < 0.05). Posteriorly stepped augmented glenoid components can improve pathologic retroversion and posterior subluxation of the humeral head in B2 and B3 glenoids, with significant improvements found in clinical outcome scores at a minimum of 2 years of follow-up in the vast majority of patients. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Relief of asthma in two patients receiving danazol for endometriosis.
This paper describes two patients with endometriosis in whom treatment with danazol resulted in a concomitant remission of asthma. Neither patient reported an association of clinical symptoms with phases of their menstrual cycle. Whether the remission was fortuitous or related to suppression of the activity of the endometriotic tissue or to the ability of danazol to increase the serum levels of two protease inhibitors that are deficient in patients with asthma remains to be determined.


Comparative structures and properties of elastic proteins.
Elastic proteins are characterized by being able to undergo significant deformation, without rupture, before returning to their original state when the stress is removed. The sequences of elastic proteins contain elastomeric domains, which comprise repeated sequences, which in many cases appear to form beta-turns. In addition, the majority also contain domains that form intermolecular cross-links, which may be covalent or non-covalent. The mechanism of elasticity varies between the different proteins and appears to be related to the biological role of the protein.


Effects of temperature and humidity on the development of eggs of Toxocara canis under laboratory conditions.
The influence of temperature and humidity on the survival and development of Toxocara canis eggs in an in vitro model system was investigated. Two soil samples were inoculated with T. canis eggs and maintained at 3% and 50% humidity and temperatures of 19-24 degrees C. Nine soil samples were inoculated with T. canis eggs of which three samples were kept at 4 degrees C with humidities at 3%, 15%, and 30%; three were maintained at 21 degrees C and three more were incubated at 34 degrees C, and at the same three humidity levels. Samples were monitored every 7 days for a total of 2 months, for the presence and development of eggs. With increasing temperature, the number of eggs undergoing development increased (P<0.01); the number of deformed eggs decreased, the number of infective eggs increased (P<0.01), and egg maturation was accelerated. A decrease in the survival of infective eggs occurred at 34 degrees C. An increase in humidity produced a rise in the number of developed eggs at all three temperatures (P<0.01). This study suggests that elevated temperatures accelerated the development as well as the degradation of eggs of T. canis, whereas the range in humidity was directly correlated with egg development.


Temperature dependent structural, vibrational and magnetic properties of K3Gd5(PO4)6.
Herein we report the evolution of the crystal structure of K3Gd5(PO4)6 in the temperature range from 20 K to 1073 K, as observed from variable temperature X-ray diffraction and Raman spectroscopic studies. K3Gd5(PO4)6 has an open tunnel containing a three dimensional structure built by [Gd5(PO4)6]3- ions which in turn are formed of PO4 tetrahedra and GdOn (n = 8 and 9) polyhedra. The empty tunnels in the structure are occupied by K+ ions and maintain charge neutrality in the lattice. Evolution of unit cell parameters with temperature shows a systematic increase with temperature. The average axial thermal expansion coefficients between 20 K and 1073 K are: αa = 10.6 × 10-6 K-1, αb = 5.5 × 10-6 K-1 and αc = 16.4 × 10-6 K-1. The evolution of distortion indices of the various coordination polyhedra with temperature indicates a gradual decrease with increasing temperature, while those of Gd2O9 and K2O8 polyhedra show opposite trends. The overall anisotropy of the lattice thermal expansion is found to be controlled largely by the effect of temperature on GdOn polyhedra and their linkages. Temperature dependent Raman spectroscopic studies indicated that the intensities and wavenumbers of most of the Raman modes decrease continuously with increasing temperature. Anharmonic analyses of Raman modes indicated that the lattice, rigid translation and librational modes have larger contributions towards thermal expansion of K3Gd5(PO4)6 compared to high frequency internal modes. The temperature and field dependent magnetic measurements indicated no long range ordering down to 2 K and the observed effective magnetic moment per Gd3+ ion and the Weiss constant are 7.91 μB and 0.38 K, respectively.


Advantages of the fixed-angle rotor for the separation of density-labelled from unlabelled proteins by isopycnic equilibrium centrifugation.
A comparison has been made between the swinging-buckets rotor and the fixed-angle rotor for density-labelling experiments. The enzymes examined were beta-galactosidase (beta-D-galactoside galactohydrolase, EC 188.8.131.52), L-phenylalanine ammonia-lyase (EC 188.8.131.52) and acid phosphatase (orthophosphoric monoester phosphohydrolase, EC 126.96.36.199); it was found that the fixed-angle rotor offered greater separation and resolution and shorter equilibration times compared with the swinging-buckets rotor at the same angular velocity. By exploiting the greater flexibility offered by the fixed-angle rotor it is possible to obtain either a 6-fold improvement in separation or a 6-fold reduction in equilibration time. The significance of these results for density-labelling work is discussed.


Study on the interaction between cannabinol and DNA using acridine orange as a fluorescence probe.
The interaction between cannabinol (CBN) and herring-sperm deoxyribonucleic acid was investigated by using acridine orange as a fluorescence probe in this work. UV-Vis spectroscopy, fluorescence spectroscopy, and DNA melting techniques were used. The fluorescence of DNA acridine orange was quenched by CBN. The results indicated that CBN can bind to DNA. The binding constant for the CBN and herring-sperm deoxyribonucleic acid was obtained at 3 temperatures, respectively. Results of molecular docking corroborated the experimental results obtained from spectroscopic investigations. The influence of ionic strength on the fluorescence properties was also investigated. The thermodynamic results indicated that hydrophobic interaction played a major role in the binding between CBN and DNA.


Blood pressure variability as well as blood pressure level is important for left ventricular hypertrophy and brachial-ankle pulse wave velocity in hypertensives.
Blood pressure (BP) variability is calculated as the standard deviation of ambulatory BP. Blood pressure variability is associated with the cardiovascular morbidity; however whether it is related to target organ damage is controversial. In this study we examined a possible relationship between the BP variability and left ventricular hypertrophy (LVH), and between BP variability and brachial-ankle pulse wave velocity (baPWV). The present study was conducted on 111 consecutive Japanese hypertensive patients who were hospitalized for the educational program in our hospital under stable sodium chloride intake (6 g/day). Blood pressure measurements were at 30-minute intervals all day. In a multivariable analysis adjusted with confounding factor, LVH was associated with 24-hour systolic BP (SBP), 24 hour diastolic BP (DBP), daytime SBP, daytime DBP, nighttime SBP, and nighttime DBP. Additionally, nighttime DBP variability was related to LVH. By the same method, baPWV as a dependent variable was related to 24-hour SBP and nighttime SBP. Furthermore, nighttime SBP variability was concerned with baPWV. The LVH was associated with not only BP level but also with nighttime DBP variability. The baPWV was also related not only to BP level but also to nighttime SBP variability.


Infant oral health education for pediatric and family practice residents.
The purpose of this study was to investigate whether an infant oral health curriculum implemented in pediatric and family medicine residency programs could improve physicians' oral health knowledge and practice behaviors and promote the age 1 dental visit. Residents and faculty members completed a baseline current practices survey and knowledge test before receiving a 1- or 2-hour training session followed by a knowledge post-test. Existing well child care forms were updated with oral health prompts to reinforce newly learned skills. At 1-year follow-up (1 YFU), participants completed a current practices survey and knowledge test. In addition to the residency programs, medical students and advanced practice registered nurses participated in baseline data collection, training, and immediate posttest data collection. A total of 245 people participated, with 78% trained in person and 22% trained via the Web. Of these, 120 were the targeted residents and faculty-of whom 82% completed the 1 YFU. Practice behaviors improved from baseline to 1 YFU, with only 28% of practitioners at baseline referring children to the dentist at age 1, compared to 73% at 1 YFU (P<.05). Knowledge scores were greater at 1 YFU than at baseline (P<.05), and the mode of training showed no difference in knowledge outcomes. Knowledge and prescribing practices regarding fluoride were poor at baseline and showed limited improvement at 1 YFU. An infant oral health education program can improve physicians' oral health knowledge and behaviors, particularly regarding promoting the age 1 dental visit. Behavior changes regarding fluoride prescribing, however, appear harder to achieve. Web-based training had similar success to in-person training.


Dietary antioxidants impact DDT resistance in Drosophila melanogaster.
Insects experience a diversity of subtoxic and/or toxic xenobiotics through exposure to pesticides and, in the case of herbivorous insects, through plant defensive compounds in their diets. Many insects are also concurrently exposed to antioxidants in their diets. The impact of dietary antioxidants on the toxicity of xenobiotics in insects is not well understood, in part due to the challenge of developing appropriate systems in which doses and exposure times (of both the antioxidants and the xenobiotics) can be controlled and outcomes can be easily measured. However, in Drosophila melanogaster, a well-established insect model system, both dietary factors and pesticide exposure can be easily controlled. Additionally, the mode of action and xenobiotic metabolism of dichlorodiphenyltrichloroethane (DDT), a highly persistent neurotoxic organochlorine insecticide that is detected widely in the environment, have been well studied in DDT-susceptible and -resistant strains. Using a glass-vial bioassay system with blue diet as the food source, seven compounds with known antioxidant effects (ascorbic acid, β-carotene, glutathione, α-lipoic acid, melatonin, minocycline, and serotonin) were orally tested for their impact on DDT toxicity across three strains of D. melanogaster: one highly susceptible to DDT (Canton-S), one mildly susceptible (91-C), and one highly resistant (91-R). Three of the antioxidants (serotonin, ascorbic acid, and β-carotene) significantly impacted the toxicity of DDT in one or more strains. Fly strain and gender, antioxidant type, and antioxidant dose all affected the relative toxicity of DDT. Our work demonstrates that dietary antioxidants can potentially alter the toxicity of a xenobiotic in an insect population.


Perfluorooctanoic acid effects on steroid hormone and growth factor levels mediate stimulation of peripubertal mammary gland development in C57BL/6 mice.
Perfluorooctanoic acid (PFOA) is a synthetic, widely used perfluorinated carboxylic acid and a persistent environmental pollutant. It is an agonist of peroxisome proliferator-activated receptor alpha (PPARalpha). Studies have shown that PFOA causes hepatocellular hypertrophy, tumorigenesis, and developmental toxicity in rodents, and some of its toxicity depends on the expression of PPARalpha. Our recent study revealed a stimulatory effect of peripubertal PFOA treatment (5 mg/kg) on mammary gland development in C57Bl/6 mice. The present study was designed to examine the underlying mechanism(s). It was found that mammary gland stimulation by PFOA was similarly observed in PPARalpha knockout and wild-type C57Bl/6 mice. The presence of ovaries was required for PFOA treatment (5 mg/kg) to stimulate mammary gland development with significant increases in the levels of enzymes involved in steroid hormone synthesis in both PFOA-treated wild-type and PPARalpha knockout mouse ovaries. PFOA treatment significantly increased serum progesterone (P) levels in ovary-intact mice and also enhanced mouse mammary gland responses to exogenous estradiol (E), P, and E + P. In addition, PFOA treatment resulted in elevated mammary gland levels of epidermal growth factor receptor (EGFR), estrogen receptor alpha, amphiregulin (Areg, a ligand of EGFR), hepatocyte growth factor, cyclin D1, and proliferating cell nuclear antigen (PCNA) in both wild-type and PPARalpha knockout mouse mammary glands. These results indicate that PFOA stimulates mammary gland development in C57Bl/6 mice by promoting steroid hormone production in ovaries and increasing the levels of a number of growth factors in mammary glands, which is independent of the expression of PPARalpha.


Symposium on the Definition of Death: Summary Statement.
This statement summarizes the conclusions of the Symposium on the Definition of Death, held at The Catholic University of America in June 2014. After providing the background and context for contemporary debates about brain death and describing the aims of the symposium, the statement notes points of unanimous and broad agreement among the participants, and highlights areas for further study.


Describing the deficits in IADLs as functional impairment of Alzheimer's disease.
Assessing the deficits in instrumental activities of daily living (IADLs) may be pivotal in understanding Alzheimer's disease (AD). Yet, the assessment of functioning in AD is often related to deficits in activities of daily living (ADLs) and assessed after manifested objective cognitive deterioration and a diagnosis of AD. Therefore, the purpose of this longitudinal, descriptive, secondary analysis is to describe the deficits in IADLs in normal-functioning elders who develop AD and in persons with mild cognitive impairment (MCI) who develop AD within a 4-year period. The study will also describe the relationship between deficits of IADLs at baseline and the progression of AD at follow-up. The sample consisted of 41 community-residing White elders (mean age = 67 +/- 8). Measurements assessed the progression of AD from normal functioning to AD (the Global Deterioration Scale) and deficits in IADLs/ADLs (the Functional Assessment Staging of AD), in cognition (Mini Mental State Examination), and in memory skills (the Guild Memory Test and Wechsler Adult Intelligence Scale). Nonparametric statistics and cross-tabulation analysis were used with an alpha of .05. Deficits in IADLs differentiated normal-functioning persons from those with MCI (LR [2, N = 401 = 9.17, p < or = .01) associated with AD progression (CV = .57, p < or = .002), and differentiated the progression of normal-functioning elders to AD (p < or = .0001). Baseline deficits in IADLs approached significance in describing AD progression at follow-up (p < or = .09). Deficits in cognition and memory skills occurred later. Assessing deficits in IADLs may significantly enhance the understanding of AD for early assessment and treatment.


Examining Muscle Regeneration in Zebrafish Models of Muscle Disease.
Skeletal muscle has a remarkable ability to regenerate following injury, which is driven by obligate tissue resident muscle stem cells. Following injury, the muscle stem cell is activated and undergoes cell proliferation to generate a pool of myoblasts, which subsequently differentiate to form new muscle fibers. In many muscle wasting conditions, including muscular dystrophy and ageing, this process is impaired resulting in the inability of muscle to regenerate. The process of muscle regeneration in zebrafish is highly conserved with mammalian systems providing an excellent system to study muscle stem cell function and regeneration, in muscle wasting conditions such as muscular dystrophy. Here, we present a method to examine muscle regeneration in zebrafish models of muscle disease. The first step involves the use of a genotyping platform that allows the determination of the genotype of the larvae prior to eliciting an injury. Having determined the genotype, the muscle is injured using a needle stab, following which polarizing light microscopy is used to determine the extent of muscle regeneration. We therefore provide a high throughput pipeline which allows the examination of muscle regeneration in zebrafish models of muscle disease.


A novel MEMS compatible lab-on-a-tube technology.
We present a novel lab-on-a-tube technology, which is a combination of three-dimensional (3D) cylindrical photolithography and nanoimprint processes, for fabricating microfunctional structures on a tiny tube substrate directly. As an example, electrochemical electrodes, which consisted of Pt work and Ag/AgCl reference electrodes, were successfully fabricated on a 330-μm-diameter polyimide capillary. Using thermal nanoimprint technology, a microdome array with a diameter of 2 μm to about 600 nm was prepared in the work and reference electrodes. The nanoimprinted domes greatly enhanced the electrochemical activity and there were much higher oxidation and reduction current peaks observed in cyclic voltammetry curves of the nanoimprinted electrode than those of the blank electrode without the nanoimprint modification. The nanoimprinted patterns exhibited complicated effects, e.g. the 600-nm-diameter dome sample has higher electrochemical activity than the 2-μm-diameter dome, while the latter has a larger surface. By using the new lab-on-a-tube technology, new bio- and nanomaterials could be integrated directly into electronic devices on tiny tube substrates so that many interesting applications could be expected in medical and life technologies.


Expanding the spectrum of Gorham Stout disease exploring a single center pediatric case series.
Gorham-Stout Disease (GSD), also named vanishing bone disease, is an ultrarare condition characterized by progressive osteolysis with intraosseous lymphatic vessel proliferation and bone cortical loss. So far, about 300 cases have been reported. It may occur at any age but more commonly affects children and young adults. The aim of this study is to retrospectively review our internal patient series and to hypothesize a diagnostic-therapeutic protocol for earlier diagnosis and treatment. Clinical datasets from our center were examined to identify all GSD patients for collection and analysis. We identified 9 pediatric cases and performed a retrospective case-series review to examine and document both diagnosis and treatment. We found that delay in diagnosis after first symptoms played a critical role in determining morbidity and that multidisciplinary care is key for proper diagnosis and treatment. Our study provides additional insight to improve the critical challenge of early diagnosis and highlights a multidisciplinary treatment approach for the most appropriate management of patients with rare GSD disease. Although GSD is an ultrarare disease, physicians should keep in mind the main clinical features since neglected cases may result in potentially fatal complications.


Definition and refinement of a region of loss of heterozygosity at 11q23.3-q24.3 in epithelial ovarian cancer associated with poor prognosis.
Previous cytogenetic and loss of heterozygosity (LOH) data suggest that disruption of chromosome 11q23-qter occurs frequently in epithelial ovarian cancer and is associated with an adverse clinicopathological phenotype. Ten polymorphic microsatellite repeat loci were analyzed by PCR from the 11q22-q25 region between D11S35 and D11S968 in 40 ovarian tumors (including 31 epithelial ovarian cancers). Two distinct regions of loss were detected, suggesting possible sites for genes involved in epithelial ovarian neoplasia: a large centromeric region between D11S35 and D11S933 (11q22-q23.3) and a telomeric 8.5-Mb region lying between D11S934 and D11S1320 (11q23.3-24.3) not previously defined. LOH of the latter region but not the former one was significantly associated with poor survival, despite all tumors in this study having LOH somewhere on chromosome 11. This analysis provides a starting point for positional cloning.


Single-cell genomic profile-based analysis of tissue differentiation in colorectal cancer.
Colorectal cancer (CRC) progression is associated with cancer cell dedifferentiation and sternness acquisition. Several methods have been developed to identify sternness signatures in CRCs. However, studies that directly measured the degree of dedifferentiation in CRC tissues are limited. It is unclear how the differentiation states change during CRC progression. To address this, we develop a method to analyze the tissue differentiation spectrum in colorectal cancer using normal gastrointestinal single-cell transcriptome data. Applying this method on 281 tumor samples from The Cancer Genome Atlas Colon Adenocarcinoma dataset, we identified three major CRC subtypes with distinct tissue differentiation pattern. We observed that differentiation states are closely correlated with anti-tumor immune response and patient outcomes in CRC. Highly dedifferentiated CRC samples escaped the immune surveillance and exhibited poor outcomes; mildly dedifferentiated CRC samples showed resistance to anti-tumor immune responses and had a worse survival rate; well-differentiated CRC samples showed sustained anti-tumor immune responses and had a good prognosis. Overall, the spectrum of tissue differentiation observed in CRCs can be used for future clinical risk stratification and subtype-based therapy selection.


[Genital actinomycosis. Diagnostic and therapeutic difficulties. Report of three cases].
Genital actinomycosis is a rare bacterial infection affecting women of child-bearing age, which is sometimes related to the use of an IUD or an intra-vaginal pessary. Nevertheless, this relationship is at best tenous and actinomycosis is not the only bacterial infection caused by IUD use. Genital actinomycosis often occurs as a pelvic tumour which is sometimes difficult to correctly diagnose and consequently treat accordingly. Rapid diagnosis is essential in order to avoid any irreparable tissue damage. Treatment of this condition consists of a combination of antibiotics and surgery to achieve complete recovery. Three cases are described.


The combination of chlorthalidone with nifedipine does not exert an additive antihypertensive effect in essential hypertensives: a crossover multicenter study.
To evaluate whether the combination of nifedipine with chlorthalidone exerts an additive antihypertensive effect when compared to single-drug treatment, 66 uncomplicated essential hypertensives, whose diastolic blood pressure was greater than 100 and less than 115 mm Hg at the end of a 1-month washout placebo period, received, according to a randomized, double-blind, crossover design, nifedipine (20 mg b.i.d.), chlorthalidone (25 mg o.d.), the two drugs combined at the same doses, and the corresponding placebo. When compared to the randomized placebo the three active treatments significantly (p less than 0.001) reduced blood pressure without changing heart rate and body weight. However, blood pressure values were similarly reduced under nifedipine and the combination and were significantly lower (p less than 0.05) than those under chlorthalidone. Moreover, the percentage of responders and normalized patients under nifedipine and the two drugs combined were similar and significantly (normalized, p less than 0.0001; responders, p less than 0.02) greater than those under chlorthalidone. Under chlorthalidone and its combination with nifedipine, plasma potassium tended to decrease and blood glucose and serum uric acid were significantly (p less than 0.05) increased. These data show that the combination of nifedipine with chlorthalidone does not exert any additive antihypertensive effect when compared to nifedipine alone and that this combination increases both blood glucose and serum uric acid. Taken together these findings indicate that the combination of a dihydropyridine calcium antagonist with a thiazide diuretic is devoid of any clinical significance in the treatment of uncomplicated essential hypertensives.


Phomoxanthone A--From Mangrove Forests to Anticancer Therapy.
Mangrove associated endophytes are treasure chests for bioprospecting especially in light of the need for new anticancer leads that are necessary to overcome drug resistance of cancer cells. This review highlights the potent anti-tumour compound phomoxanthone A (PXA), which represents a tetrahydroxanthone atropisomer derived from the mangrove-associated fungus Phomopsis longicolla. PXA displayed strong anti-tumour activity when tested against a panel of solid (including cisplatin resistant) tumour cell lines or of blood cancer cell lines with IC50 values in the submicromolar range whereas it was up to 100 folds less active against peripheral blood mononuclear cells (PBMC) from healthy donors. The anti-tumour activity of PXA was demonstrated to be due to an induction of caspase 3 dependent apoptosis. At the same time PXA was shown to activate immune cells such as murine T-lymphocytes, NK cells and macrophages which might help in fighting resistance during cancer chemotherapy. Structure activity studies that involved several naturally occurring as well as semisynthetic derivatives of PXA indicated the position of the biaryl linkage and the acetyl substituents as structural features that are important for the activity of this natural product.


Eye fluke-induced cataract formation in fish: quantitative analysis using an ophthalmological microscope.
We examined the parasite-induced cataract formation in rainbow trout (Oncorhynchus mykiss) using slit-lamp microscopy to determine the relationship between cataract intensity and number of Diplostomum spathaceum parasites that were established in the lens. Cataract intensity increased significantly with parasite burden, but was also affected by the pattern of exposure to the parasite cercariae. The slit-lamp methodology proved useful in scoring the cataracts since it provides a 3-dimensional view into the lens and gives an actual picture of the location and intensity of the cataracts, which allows detailed investigations of mechanisms underlying cataract formation in various fish species. Potential applications of the method in fish farming and parasitological studies are discussed.


Characterization of the Weekly External Load Profile of Professional Soccer Teams from Portugal and the Netherlands.
The purpose of this study was to analyze the day-to-day variance of a typical weekly external training workload of two professional soccer teams from different countries. Twenty-nine players from two professional teams from Portugal and the Netherlands participated in this study. The players' external load was monitored for 7 weeks, by means of portable GPS devices (10 Hz, JOHAN, Noordwijk, Netherlands). Results revealed that match day -1 (MD-1), i.e. the training day before a match, had significantly (p = 0.001) less training volume (4584.50 m) than the other days. MD-5 (training five days before a match), MD-4 (four days before a match) and MD-3 (three days before a match) were the most intense (390.83, 176.90 and 247.32 m of sprinting distance, respectively) and with large volume (7062.66, 6077.30 and 6919.49 m, respectively). Interestingly, significant differences were found between clubs of different countries (p < 0.05) with the Portuguese team showing significantly higher intensity (sprinting distance) and volume (total distance) in all days with exception of MD-1 than the Dutch team. The results of this study possibly allow for the identification of different training workloads and tapering strategies between countries in relation to volume and intensity. It should be noted, however, that both clubs used a significant tapering phase in the last two days before the competition in an attempt to reduce residual fatigue accumulation.


Hyponatremia and long-term outcomes in chronic heart failure--an observational study from the Duke Databank for Cardiovascular Diseases.
Hyponatremia is a well known predictor of short-term outcomes in heart failure (HF); however, its impact on long-term survival in HF patients with systolic dysfunction is not well established. Using the Duke Databank for Cardiovascular Diseases, we identified 1,045 patients with HF and systolic dysfunction undergoing cardiac catheterization from January 2000 through December 2008. The effect of hyponatremia as independent predictor of all-cause death and cardiovascular death/rehospitalization was examined using a multivariable Cox proportional regression model. Hyponatremia was present in 107/1,045 patients (10.2%). Hyponatremic patients were older, more likely to be anemic, with higher heart rate and levels of blood urea nitrogen, lower blood pressure, and more severe HF. Using an unadjusted analysis, hyponatremia was associated with higher risk of all-cause death (hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.44-2.49; P < .0001) and of cardiovascular death/rehospitalization (HR 1.40, 95% CI 1.11-1.77; P = .005) at 4.5 years. When entered into a multivariable Cox model, hyponatremia remained significant for all-cause death (HR 1.42, 95% CI 1.07-1.88) and for cardiovascular death/rehospitalization (HR 1.45, 95% CI 1.14-1.86). Hyponatremia is relatively common in HF patients with LV dysfunction and is independently associated with increased risk of all-cause mortality and cardiovascular mortality/rehospitalization.


Violence and sexual dysfunction among infertile Egyptian women.
To evaluate domestic violence and sexual dysfunction in infertile women. We recruited women complaining of infertility (primary or secondary infertility). A control group of fertile women attending the outpatient clinic for any concern was recruited. Domestic violence was evaluated using the Arabic validated NorVold Domestic Abuse Questionnaire (NORAQ). Female sexual function was evaluated using the Arabic validated female sexual function index. There was no significant difference between both groups in rates of exposure to violence (p-value 0.830). Primary infertility was a significant contributing factor in infertile women's exposure to violence (p-value 0.001). All the studied population had female sexual dysfunction, with more dysfunction was reported by the infertile women (total score 18.87 ± 5.92, 19.51 ± 5.42, p-value 0.072). They differed significantly in arousal (2.83 ± 1.33, 3.13 ± 1.29, p-value 0.001) and satisfaction (3.98 ± 1.27, 4.28 ± 1.28, p-value 0.003) which were impaired in infertile women. The recruited infertile women were exposed to violence. Emotional abuse was the most common reported type of violence. Sexual dysfunction was reported in the entire studied population with no significant difference relating to fertility.


Purification and characterization of an extracellular 29-kilodalton phospholipase C from Listeria monocytogenes.
We purified and characterized an extracellular phospholipase produced by Listeria monocytogenes. This enzyme was separated as a homogeneous protein of 29 kDa by chromatography on DEAE-52 cellulose and Bio-Gel P100 columns. It is a zinc-dependent phospholipase C (PLC) that is mainly active at pH 6 to 7 and expresses lecithinase activity and a weaker sphingomyelinase activity. The exoenzyme also hydrolyzed phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and sphingomyelin but not phosphatidylinositol. It was distinct from the 36-kDa phosphatidylinositol PLC produced by L. monocytogenes and from the L. ivanovii sphingomyelinase. The pure protein expressed a weak, calcium-independent hemolytic activity and was not toxic in mice. Western immunoblot analysis using a rabbit immune serum raised against the enzyme showed that all virulent strains of L. monocytogenes tested produced in the culture supernatant a 29-kDa PLC. In contrast, no proteins antigenically related to the 29-kDa PLC were detected in supernatants of L. ivanovii, L. seeligeri, L. innocua, or L. welshimeri. The role in virulence of the 29-kDa PLC specifically produced by L. monocytogenes remains to be established.


Skin necrosis in a critically ill patient due to a blood pressure cuff.
The non-invasive method of blood pressure measurement is regarded as a safe procedure and the reports of any serious complications are rare. We report a unique case of extensive skin necrosis due to an intermittently inflating blood pressure cuff in a 65-year-old critically ill lady following a third time redo mitral valve surgery. A brief review of the literature on complications associated with noninvasive method of measurement of blood pressure is presented along with possible mechanisms of skin injury and ways to avoid it.