Facilitators and Barriers to Recruiting Ambulatory Oncology Practices Into a Large Multisite Study: Mixed Methods Study.
Practice-based research is essential to generate the data necessary to understand outcomes in ambulatory oncology care. Although there is an increased interest in studying ambulatory oncology care, given the rising patient volumes and complexity in those settings, little guidance is available on how best to recruit ambulatory oncology practices for research. This paper aimed to describe the facilitators and barriers to recruiting ambulatory oncology practices into a large multisite study. Using a mixed methods design, we sought to recruit 52 ambulatory oncology practices that have participated in a state-wide quality improvement collaborative for the quantitative phase. We used 4 domains of the Consolidated Framework for Implementation Research (CFIR) to describe facilitators and barriers to recruitment. We successfully recruited 28 of the 52 collaborative-affiliated practices, collecting survey data from 2223 patients and 297 clinicians. Intervention attributes included multimodal outreach and training activities to assure high fidelity to the data collection protocol. The implementation process was enhanced through interactive training and practice-assigned champions responsible for data collection. External context attributes that facilitated practice recruitment included partnership with a quality improvement collaborative and the inclusion of a staff member from the collaborative in our team. Key opinion leaders within each practice who could identify challenges to participation and propose flexible solutions represented internal context attributes. We also reported lessons learned during the recruitment process, which included navigating diverse approaches to human subjects protection policies and understanding that recruitment could be a negotiated process that took longer than anticipated, among others. Our experience provides other researchers with challenges to anticipate and possible solutions for common issues. Using the CFIR as a guide, we identified numerous recruitment barriers and facilitators and devised strategies to enhance recruitment efforts. In conclusion, researchers and clinicians can partner effectively to design and implement research protocols that ultimately benefit patients who are increasingly seeking care in ambulatory practices.


Too large to fit? Recent developments in macromolecular imprinting.
Molecular imprinting involves the synthesis of polymers in the presence of a template to produce complementary binding sites with specific recognition ability. The technique has been successfully applied as a measurement and separation technology, producing a uniquely robust and antibody-like polymeric material. Low molecular weight molecules have been extensively exploited as imprint templates, leading to significant achievements in solid-phase extraction, sensing and enzyme-like catalysis. By contrast, macromolecular imprinting remains underdeveloped, principally because of the lack of binding site accessibility. In this review, we focus on the most recent developments in this area, not only covering the widespread use of biological macro-templates but also highlighting the emerging use of synthetic macro-templates, such as dendrimers and hyperbranched polymers.


Studying the knowledge, attitude and practice of antibiotic misuse among Alexandria population.
To assess knowledge, attitude and practice (KAP) of antimicrobial self-medication among a convenience sample of population in Alexandria, Egypt. A descriptive cross-sectional study using a self-administrated semi-constructed questionnaire. A convenience sample of 359 participants was studied using appropriate consent. The questionnaire had four sections: demographics, KAP, professional medical knowledge and attitude of children caregivers toward antimicrobial self-medication. The questionnaire was initially constructed in English and then translated into its final Arabic version. The Arabic version was pilot-tested and face-validated. Descriptive and quantitative analysis were performed using SPSS (V.20.0). Approximately 64% (231) of the studied population used antibiotics without prescription in the past 12 months. This was significantly correlated with female gender and lack of knowledge. The main reason for self-medication was due to saving time and effort (109, 47%) followed by not preferring doctor visits (89, 39%). More than 60% of cases used amoxicillin-clavulanic acid. The main sources of antibiotics were leftovers from previously prescribed pharmaceuticals and those purchased from community pharmacies. 85 participants were young children caregivers of which 18 (21%) reported administering antibiotics to their children without consulting a physician. Out of 115 who claimed attaining medical background, only 30 (26%) managed to answer section 3 correctly with 23 of them reporting antibiotic self-medication. This study showed an increased tendency towards antibiotic self-medication among Alexandrian adults and children that was not significantly decreased in population with medical background. The reasons discussed within the study should be further addressed to decrease such practice.


Transient massive trimethylaminuria associated with food protein-induced enterocolitis syndrome.
Trimethylaminuria (TMAU) is an autosomal recessive disease caused by excessive excretion into body fluids and breath of unoxidized trimethylamine (TMA) derived from the enterobacterial metabolism of dietary precursors. The condition is caused by deficiency of flavin-containing monooxygenase 3 (FMO3) which leads to impairment of hepatic TMA oxidation to the odorless trimethylamine N-oxide. Secondary TMAU is due to substrate overload in individuals with genetically determined reduced enzyme activity. Food protein-induced enterocolitis syndrome (FPIES) is characterized by recurrent episodes of emesis, diarrhea, dehydration, and lethargy after ingestion of offending foods. Its pathophysiology involves local non-IgE-mediated inflammation of the gastrointestinal tract, which leads to increased intestinal permeability. We report on an 8-month-old male who presented with typical episodes of FPIES associated with intense fish-like body odor. Further investigation in our patient revealed massive urinary TMA excretion during acute FPIES presentation and complete normalization between these episodes. The patient was found to be heterozygous for a novel, paternally inherited nonsense p.Tyr331X mutation and for two maternally inherited common polymorphisms, E158K and E308G, in the FMO3 gene. We propose that our patient was able to cope with the daily burden of TMA, but when challenged with substrate overload, he failed to oxidize TMA due to limited reserve enzyme capacity. We discuss the pathophysiology of TMAU and FPIES and suggest potential mechanisms for the clinical and biochemical findings. Our report illustrates the complex interplay of genetic and environmental factors in TMAU and sheds light on the pathophysiology of FPIES.


Structural Basis of Stereospecific Vanadium-Dependent Haloperoxidase Family Enzymes in Napyradiomycin Biosynthesis.
Vanadium-dependent haloperoxidases (VHPOs) from Streptomyces bacteria differ from their counterparts in fungi, macroalgae, and other bacteria by catalyzing organohalogenating reactions with strict regiochemical and stereochemical control. While this group of enzymes collectively uses hydrogen peroxide to oxidize halides for incorporation into electron-rich organic molecules, the mechanism for the controlled transfer of highly reactive chloronium ions in the biosynthesis of napyradiomycin and merochlorin antibiotics sets the Streptomyces vanadium-dependent chloroperoxidases apart. Here we report high-resolution crystal structures of two homologous VHPO family members associated with napyradiomycin biosynthesis, NapH1 and NapH3, that catalyze distinctive chemical reactions in the construction of meroterpenoid natural products. The structures, combined with site-directed mutagenesis and intact protein mass spectrometry studies, afforded a mechanistic model for the asymmetric alkene and arene chlorination reactions catalyzed by NapH1 and the isomerase activity catalyzed by NapH3. A key lysine residue in NapH1 situated between the coordinated vanadate and the putative substrate binding pocket was shown to be essential for catalysis. This observation suggested the involvement of the ε-NH2, possibly through formation of a transient chloramine, as the chlorinating species much as proposed in structurally distinct flavin-dependent halogenases. Unexpectedly, NapH3 is modified post-translationally by phosphorylation of an active site His (τ-pHis) consistent with its repurposed halogenation-independent, α-hydroxyketone isomerase activity. These structural studies deepen our understanding of the mechanistic underpinnings of VHPO enzymes and their evolution as enantioselective biocatalysts.


Burn injuries among children aged up to seven years.
We investigated characteristics of burns in children aged up to seven years and hospitalized at our Burn Unit between 1 January 2000 and 31 December 2007 in order to detect risk factors and prepare a program for prevention of burn injuries in children. There were 119 boys and 81 girls (ratio 1:0.67) and the mean total body surface area burned was 16.6 +/- 12.5%. Sixty-nine percent (n = 138) of the burn-injured children were under three years old. Scalds accounted for more than 60% of the pediatric burns occurring in all age groups. The anterior trunk was the most frequently affected body part (51.5%). The overall mortality rate was 4% (8 deaths). The children included in this study were younger than seven years and they were supposed to be under the care of their parents. Parental neglect might have played a role in burn injuries in these children. In developing countries like Turkey, parents should be offered education about prevention of burn injuries in childhood.


Genetic influences on smoking behavior and nicotine dependence: a review.
Molecular epidemiologic studies suggest genetic factors in the etiology of smoking behavior. Dopamine receptor genes, transporter genes (serotonin and dopamine), and other genes related to metabolism of nicotine are plausible functional candidate genes. Research examining the role of allelic variation in those genes is being actively pursued with respect to nicotine dependence as well as personality characteristics and mental disorders. Some of these genes were reported to be connected with schizophrenia. Although nicotine dependence itself is one of the mental disorders according to the fourth edition of Diagnostic and Statistical Manual of Mental Disorders and the World Health Organization's International Statistical Classification of Diseases and Related Health Problems-10 nomenclature, the high comorbidity between nicotine dependence and other mental disorders such as schizophrenia or affective disorders has been noted. Therefore, the relationship between those mental disorders and tobacco addiction should be cleared up considering the interactive effect of genetic and environmental factors.


Pathologizing Ugliness: A Conceptual Analysis of the Naturalist and Normativist Claims in "Aesthetic Pathology".
Pathologizing ugliness refers to the use of disease language and medical processes to foster and support the claim that undesirable features are pathological conditions requiring medical or surgical intervention. Primarily situated in cosmetic surgery, the practice appeals to the concept of "aesthetic pathology", which is a medical designation for features that deviate from some designated aesthetic norms. This article offers a two-pronged conceptual analysis of aesthetic pathology. First, I argue that three sets of claims, derived from normativist and naturalistic accounts of disease, inform the framing of ugliness as a disease. These claims concern: (1) aesthetic harms, (2) aesthetic dysfunction, and (3) aesthetic deviation. Second, I introduce the notion of a hybridization loop in medicine, which merges the naturalist and normative understanding of the disease that potentially enables pathologizing practices. In the context of cosmetic surgery, the loop simultaneously promotes the framing of beauty ideals as normal biological attributes and the framing of normal appearance as an aesthetic ideal to legitimize the need for cosmetic interventions. The article thus offers an original discussion of the conceptual problems arising from a specific practice in cosmetic surgery that depicts ugliness as the disease.


A series of vascular tumors and tumorlike lesions of the bladder.
Vascular tumors of the bladder are rare and a subject of small series and case reports. We retrospectively identified vascular tumors of the urinary bladder from the consultation files from one of the authors. We identified 13 lesions that included 3 hemangiomas, 3 intravascular papillary endothelial hyperplasias (Masson vegetant hemangioendotheliomas), 2 arteriovenous malformations (AVMs), 1 epithelioid hemangioendothelioma (EHE), and 4 angiosarcomas. One of the angiosarcomas was associated with conventional high-grade urothelial carcinoma (sarcomatoid carcinoma). All patients were adults with a range in age from 18 to 85 years old (mean 63.3). There was no statistical difference among the various lesions in terms of age, although angiosarcomas tended to arise in older patients (mean 71 y vs. 60 y of the remainder). Hematuria was the most common presentation of both benign and malignant lesions. Other symptoms included voiding irritation, pelvic pain, and obstruction. Histologically, benign and malignant lesions were similar to their counterparts in other organ systems. Two hemangiomas were of the capillary type and a third one of the cavernous subtype. They measured 1.1, 2.4, and 3.2 cm. Both AVMs were clinically large broad-based masses measuring 5.5 and 5.8 cm in greatest diameter. One of the AVMs was associated with pseudoepitheliomatous hyperplasia of the urothelium. All 3 patients with Masson lesion had history of radiation therapy for other causes. These presented as raised lesions and were all <1.0 cm. Patients with hemangiomas, papillary endothelial hyperplasias, and AVM had an invariably benign prognosis and needed no further therapy. These benign lesions had consistent involvement of the submucosa and spared the muscularis propria of the organ. All cases of angiosarcoma and EHE involved the muscularis propria. Two of four patients with angiosarcoma had a history of prior radiation therapy and all 4 were dead of disease at 6 months. Angiosarcomas measured 3, 4.5, 5, and 5.8 cm in greatest diameter at cystoscopy. The patient with EHE had a single nodule treated by transurethral resection of the bladder and no evidence of disease at 4 years of follow-up. None of the patients experienced marked gross hematuria that resulted in morbidity or mortality. A wide spectrum of benign, intermediate malignant, and malignant vascular lesions primarily involved the bladder. Despite the potential for marked hemorrhage, none of the tumors resulted in marked hematuria. Papillary endothelial hyperplasia occurs in the bladder and must be differentiated from angiosarcoma, which has a rapidly fatal outcome.


Physical activity associated with prayer regimes improves standing dynamic balance of healthy people.
[Purpose] Preparing for prayers, practicing religious meditation and performing prayers are believed to stimulate the visual, vestibular and somatosensory systems, which provide the sensory information that influences human balance. The purpose of this study was to determine the effect of the Islamic prayer regime on balance. [Subjects and Methods] Sixty healthy male subjects with a mean age of 31 ± 5 years and a mean body mass index of 27 ± 2 kg/cm(2) voluntarily participated in this study. The subjects were divided into two equal groups: one group of subjects who regularly practiced Islamic prayer, and another group of non-practicing subjects. The dynamic balance of individuals in both groups was measured using a Balance Master. [Results] Adult healthy subjects practicing Islamic prayer regimes exhibited statistically significantly better dynamic balance than the non-practicing healthy subjects. [Conclusions] The results of this study support the hypothesis that religious meditation and prayers benefit human physiological function, especially balance.


Expression level of proteoglycan, collagen and type II collagen in osteoarthritis rat model is promoted and degradation of cartilage is prevented by glucosamine methyl ester.
In the current study, the effect of glucosamine methyl ester on cartilage degeneration in osteoarthritis rat model was investigated. Forty Sprague-Dawley rats were assigned into 5 groups of 8 animals each. Osteoarthritis was induced in 4 groups using medial parapatellar incision followed by anterior cruciate ligament transection and meniscectomy. Normal and model osteoarthritis groups were given normal saline. The three treatment groups received 2, 5 and 10 mg/kg doses of glucosamine methyl ester daily for one month. Microscopic examination of the knee cartilage showed a significant reduction in degeneration score in the treatment groups. Enzyme-linked immunosorbent assay revealed inhibition of interleukin-1β expression and nitric oxide generation on treatment with glucosamine methyl ester. Expressions of matrix metalloproteinase-3 and -13 in the treatment groups were significantly lower compared to the model osteoarthritis group. Polymerase chain reaction revealed an increased expression of tissue inhibitor of metalloproteinases 1 on treatment of rats with glucosamine methyl ester. In the osteoarthritis rats treated with various doses of glucosamine methyl ester staining, the level of toluidine blue and Masson's trichrome increased. In addition, the level of type II collagen was also higher in the rats of treatment group. The level of proteoglycan, collagen and type II collagen in OA rats treated with 10 mg/kg doses was ~3.2- (p<0.01), 2.4- (p<0.02), and 3.6- (p<0.05) fold, respectively higher compared to the untreated animals. Glucosamine methyl ester, therefore, prevents degeneration of cartilage in osteoarthritis rats. It exhibits its effect by promoting proteoglycan, collagen, type II collagen, tissue inhibitor of metalloproteinases 1, and decreasing matrix metalloproteinase. Therefore, glucosamine methyl ester exhibits therapeutic effect against osteoarthritis.


Initial review of Electronic Residency Application Service charts by orthopaedic residency faculty members. Does applicant gender matter?
Orthopaedic surgery is a male-dominated field. As of 1998, women accounted for 42% of medical school graduates, yet only 6.9% of the total number of orthopaedic residents were female. The purpose of our study was to determine whether the Electronic Residency Application Service charts of female candidates for orthopaedic residencies are ranked lower by faculty reviewers than are those of male candidates with similar qualifications. After we obtained permission from the applicants, the Electronic Residency Application Service applications submitted by ninety male and ten female candidates for admission to a university orthopaedic residency program for the 1998 National Residency Matching Program were randomly divided into ten groups, consisting of the charts of nine male candidates and one female candidate. Each chart from a female candidate was altered into a "male" version, in which all names and personal pronouns were changed but which was otherwise identical to the original female version. Therefore, each group of ten charts existed as a paired set: one containing the true female chart and one, the altered "male" chart. The paired sets acted as their own control. One hundred and twenty-one faculty reviewers from fourteen orthopaedic residency programs around the United States each reviewed either the "male" or the female version of one set, without knowledge of the goals of the study, and ranked the ten charts in the order in which they would like to have the candidates as residents in their own programs. Each version of the sets was reviewed by at least five separate reviewers. Reviewers at a given institution were randomized to review different sets, so that there was no overlap among them. The rankings of the female-"male" pairs were compared with use of a standard paired t test. No significant difference was detected in the rankings of the female and "male" charts (p = 0.5). The mean difference in rankings was -0.33, with a 95% confidence interval ranging from -1.41 (favoring females) to 0.74 (favoring "males"). The low percentage of female residents is not due to bias against female applicants in the initial chart-review phase of the orthopaedic residency selection process. It is possible that bias is introduced in other stages of the selection process, such as the interview.


DNA-centered approaches to characterize regulatory protein-DNA interaction complexes.
Gene regulation is mediated by site-specific DNA-binding proteins or transcription factors (TFs), which form protein complexes at regulatory loci either to activate or repress the expression of a target gene. The study of the dynamic properties of these regulatory DNA-binding complexes has so far been dominated by protein-centered methodologies, aiming to characterize the DNA-binding behavior of one specific protein at a time. With the emerging evidence for a role of DNA in allosterically influencing DNA-binding protein complex formation, there is renewed interest in DNA-centered approaches to capture protein complexes on defined regulatory loci and to correlate changes in their composition with alterations in target gene expression. In this review, we present the current state-of-the-art in such DNA-centered approaches and evaluate recent technological improvements in the purification as well as in the identification of regulatory DNA-binding protein complexes within or outside their biological context. Finally, we suggest possible areas of improvement and assess the putative impact of DNA-centered methodologies on the gene regulation field for the forthcoming years.


Acellular biomaterials: an evolving alternative to cell-based therapies.
Acellular biomaterials can stimulate the local environment to repair tissues without the regulatory and scientific challenges of cell-based therapies. A greater understanding of the mechanisms of such endogenous tissue repair is furthering the design and application of these biomaterials. We discuss recent progress in acellular materials for tissue repair, using cartilage and cardiac tissues as examples of applications with substantial intrinsic hurdles, but where human translation is now occurring.


The truly healthy adult survivor of childhood cancer: inside feelings and behaviors.
People cured from a cancer are not only the previous patients out from the dark tunnel of the disease, in particular if we speak of youngsters. In order for a person to be considered completely cured of childhood cancer, his/her physical conditions, as well as the many associated psychological and social issues must be evaluated. Nowadays, the majority of sick children can expect to be cured, and the number of adult survivors is rapidly becoming a new population requiring special care. Most of them appear to lead normal adult lives. They have obtained high school degrees, good jobs, and several have families and children. Nevertheless, a small percentage show some psychological or social problems, such as anxiety, depression, fear of the future or of relapse, fear of a second primary, or sterility. The most vulnerable among them include females, people in poor financial conditions, the unemployed, and those with low education. There are still some open questions. What will their old age be like? Are they really cured? The most important data in the literature are reported herein. Post-traumatic stress disorder is also discussed. We believe that, in the future, survivors will have two possible outcomes which will be related to the risk of disease and treatment. Those who suffered from low and standard risk disease will reach and enjoy a normal life, while those who underwent very aggressive treatment, with or without stem cell transplantation, might have to cope with a more vulnerable life. We mainly stress the need to avoid all types of psychological and social distress. We recommend providing patients and their families with the information they need and strengthening their coping ability starting from the time of diagnosis and carrying on throughout the whole treatment period.


Antiangiogenic therapy with anti-vascular endothelial growth factor modalities for diabetic macular oedema.
Diabetic macular oedema (DMO) is a common complication of diabetic retinopathy. Although grid or focal laser photocoagulation has been shown to reduce the risk of visual loss in DMO or clinically significant macular oedema (CSMO), vision is rarely improved. Antiangiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) modalities has recently been proposed for improving vision in people with DMO. To assess the effectiveness, safety and cost-effectiveness of anti-VEGF therapy for preserving or improving vision in people with DMO. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 6), MEDLINE (January 1946 to June 2012), EMBASE (January 1980 to June 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 13 June 2012. We included randomised controlled trials (RCTs) comparing any antiangiogenic drugs with an anti-VEGF mechanism of action versus another treatment, sham treatment, or no treatment in patients with DMO. We also included economic evaluations to assess cost-effectiveness. Two review authors independently extracted the data. The risk ratio (RR) of visual loss and visual gain of three or more lines was estimated at least six months after treatment. Each economic analysis was described narratively using a structured format. Eleven studies provided data on three comparisons of interest in this review. We based our conclusions on the RR of gain or loss of three or more lines of vision at about one year, which was more consistently reported as follow-up.Compared with sham treatment, there was evidence of moderate quality in three studies (497 participants, follow-up 8 to 12 months) that antiangiogenic therapy (pegaptanib: two studies, 246 participants; ranibizumab: one study, 151 participants) doubled and, respectively, halved, the chance of gaining or losing three or more lines of vision (RR: 2.19, 95% confidence interval (CI) 1.36 to 3.53; RR: 0.28, 95% CI: 0.13 to 0.59). In meta-analyses, the benefit was larger for ranibizumab compared to pegaptanib, but no significant subgroup difference could be demonstrated regarding our primary outcome.Compared with grid laser photocoagulation, there was evidence of moderate quality that antiangiogenic therapy (bevacizumab: two studies, 167 participants; ranibizumab: two studies, 300 participants; aflibercept: one study, 221 participants, 89 used for data extraction) more than doubled and, respectively, reduced by at least two thirds, the chance of gaining or losing three or more lines of vision (RR: 3.20, 95% CI 2.07 to 4.95 and RR: 0.13, 95% CI: 0.05 to 0.34, respectively). In meta-analyses, no significant subgroup difference could be demonstrated between bevacizumab, ranibizumab and aflibercept regarding our primary outcome, but, again, there was little power to detect a difference.Compared with grid laser photocoagulation alone, there was high quality evidence that ranibizumab plus photocoagulation (three studies, 783 participants) doubled and, respectively, at least halved, the chance of gaining or losing three or more lines of vision (RR: 2.11, 95% CI 1.67 to 2.67; RR: 0.29, 95% CI: 0.15 to 0.55).Systemic and ocular adverse events were rare in the included studies. Meta-analyses conducted for all antiangiogenic drugs compared with either sham or photocoagulation (nine studies, 104 events in 2159 participants) did not show a significant difference regarding arterial thromboembolic events (RR: 0.85 (0.56 to 1.28). Similarly, no difference was suggested regarding overall mortality (53 events, RR: 0.95 (0.52 to 1.74), but clinically significant differences could not be ruled out. There is moderate quality evidence that antiangiogenic drugs provide a definite, but small, benefit compared to current therapeutic options for DMO, i.e. grid laser photocoagulation, or no treatment when laser is not an option. The quality and quantity of the evidence was larger for ranibizumab, but there was little power to investigate drug differences. Most data were obtained at one year, and a long-term confirmation is needed, since DMO is a chronic condition. Safety of both drug and the intravitreal injection procedure were good in the trials, but further long-term data are needed to exclude small, but clinically important differences regarding systemic adverse events.


SMRT analysis of MTOC and nuclear positioning reveals the role of EB1 and LIC1 in single-cell polarization.
In several migratory cells, the microtubule-organizing center (MTOC) is repositioned between the leading edge and nucleus, creating a polarized morphology. Although our understanding of polarization has progressed as a result of various scratch-wound and cell migration studies, variations in culture conditions required for such assays have prevented a unified understanding of the intricacies of MTOC and nucleus positioning that result in cell polarization. Here, we employ a new SMRT (for sparse, monolayer, round, triangular) analysis that uses a universal coordinate system based on cell centroid to examine the pathways regulating MTOC and nuclear positions in cells plated in a variety of conditions. We find that MTOC and nucleus positioning are crucially and independently affected by cell shape and confluence; MTOC off-centering correlates with the polarization of single cells; acto-myosin contractility and microtubule dynamics are required for single-cell polarization; and end binding protein 1 and light intermediate chain 1, but not Par3 and light intermediate chain 2, are required for single-cell polarization and directional cell motility. Using various cellular geometries and conditions, we implement a systematic and reproducible approach to identify regulators of MTOC and nucleus positioning that depend on extracellular guidance cues.


Endoscopic evaluation of the colorectum in patients presenting with haematochezia at korle-bu teaching hospital accra.
Colorectal endoscopy is the gold standard investigation of the large bowel in patients with rectal bleeding and is employed as a means of secondary prevention of colorectal cancer. To determine the frequency of benign lesions and carcinomas in patients who underwent colorectal endoscopy because of rectal bleeding and to evaluate the role of endoscopy in secondary prevention of colorectal carcinoma in our centre. A retrospective study was undertaken on patients who underwent colorectal endoscopy between January 1995 and December 2000 for rectal bleeding. Five hundred and ninety six (596) patients were studied. Males were 403 and females 93, mean age 50.9 (SD 7.07). Three hundred and ten patients (52%) had rigid proctosigmoidoscopy, flexible sigmoidoscopy 105 (17.6%) and colonoscopy 181 (30.4%). Of those who had colonoscopy complete examination of the colon was achieved in 55 patients (30.4%). Those in whom colonoscopy was incomplete had double contrast barium enema. Haemorrhoids were the commonest disease diagnosed, 316 patients (53%). Colorectal carcinoma 39 patients (6.7%), non-specific colitis 34 patients (5.7%), diverticular disease 27 patients (4.5%) and adenomatous polyps 17 patients (2.9%) were the next common disease. Less common conditions were ulcerative colitis, rectal schistosomiasis and angiodysplasia. In 125 patients (21.0) the cause of bleeding could not be found. An appreciable number of the patients with rectal bleeding had serious pathology that was diagnosed early by endoscopy confirming the important role of endoscopy in secondary prevention of colorectal carcinoma. The low success rate of full colonoscopy underscores the need for training in this procedure.


Pancreatic beta-cell web: its possible role in insulin secretion.
A cortical band of fine microfilaments is consistently observed in the beta cells of the rat pancreas. Alteration of this cell web by cytochalasin B is associated with an enhancement of glucose-induced secretion of insulin by isolated islets. The microfilamentous web of the beta cell may play an important role in the emiocytosis of insulin secretory granules, by controlling their access to the cell membrane.


Central sensory-motor crosstalk in the neural gut-brain axis.
The neural gut-brain axis consists of viscerosensory and autonomic motor neurons innervating the gastrointestinal (GI) tract. Sensory neurons transmit nutrient-related and non-nutrient-related information to the brain, while motor neurons regulate GI motility and secretion. Previous research provides an incomplete picture of the brain nuclei that are directly connected with the neural gut-brain axis, and no studies have thoroughly assessed sensory-motor overlap in those nuclei. Our goal in this study was to comprehensively characterize the central sensory and motor circuitry associated with the neural gut-brain axis linked to a segment of the small intestine. We injected a retrograde (pseudorabies; PRV) and anterograde (herpes simplex virus 1; HSV) transsynaptic viral tracer into the duodenal wall of adult male rats. Immunohistochemical processing revealed single- and double-labeled cells that were quantified per nucleus. We found that across nearly all brain regions assessed, PRV + HSV immunoreactive neurons comprised the greatest percentage of labeled cells compared with single-labeled PRV or HSV neurons. These results indicate that even though sensory and motor information can be processed by separate neuronal populations, there is neuroanatomical evidence of direct sensory-motor feedback in the neural gut-brain axis throughout the entire caudal-rostral extent of the brain. This is the first study to exhaustively investigate the sensory-motor organization of the neural gut-brain axis, and is a step toward phenotyping the many central neuronal populations involved in GI control.


The effects of inorganic additives to calcium phosphate on in vitro behavior of osteoblasts and osteoclasts.
This study describes a medium-throughput system based on deposition of calcium phosphate films in multi-well tissue culture plates that can be used to study the effect of inorganic additives on the behavior of osteoblasts and osteoclasts in a standardized manner. All tested elements, copper, zinc, strontium, fluoride and carbonate were homogenously deposited into calcium phosphate films in varying concentrations by using a biomimetic approach. The additives affected morphology and composition of calcium phosphate films to different extent, depending on the concentration used. The effect on proliferation and differentiation of MC3T3-E1 osteoblasts depended on the compound and concentration tested. In general, copper and zinc ions showed an inhibitory effect on osteoblast proliferation, the effect of strontium was concentration dependent, whereas films containing fluoride and carbonate, respectively, augmented osteoblast proliferation. Copper and zinc had no effect or were mild inhibitory on osteoblast differentiation, while strontium, fluoride and carbonate ions demonstrated a clear decrease in differentiation in comparison to the control films without additives. Primary osteoclasts cultured on calcium phosphate films containing additives showed a significantly decreased resorptive activity as compared to the control, independent on the element incorporated. No cytotoxic effect of the elements in the concentrations tested was observed. The system presented in this study mimics bone mineral containing trace elements, making it useful for studying fundamental processes of bone formation and turnover. The present results can be used for modifying bone graft substitutes by addition of inorganic additives in order to affect their performance in bone repair and regeneration.


Mosaic zebrafish transgenesis for evaluating enhancer sequences.
The completion of the human genome sequence, along with that of many other species, has highlighted the challenge of ascribing specific function to non coding sequences. One prominent function carried out by the non coding fraction of the genome is to regulate gene transcription; however, there are no effective methods to broadly predict cis-regulatory elements from primary DNA sequence. We have developed an efficient protocol to functionally evaluate potential cis-regulatory elements through zebrafish transgenesis. Our approach offers significant advantages over cell-culture based techniques for developmentally important genes, since it provides information on spatial and temporal gene regulation. Conversely, it is faster and less expensive than similar experiments in transgenic mice, and we routinely apply it to sequences isolated from the human genome. Here we demonstrate our approach to selecting elements for testing based on sequence conservation and our protocol for cloning sequences and microinjecting them into zebrafish embryos.


Physical fighting among school-going Portuguese adolescents: social and behavioural correlates.
The purpose of this study was to estimate the frequency and to assess the determinants of physical fighting among Portuguese school-going adolescents. A cross-sectional evaluation of urban adolescents born in 1990 and enrolled in public and private schools of Porto was performed in 2007. We identified 3161 17-year-old eligible adolescents and 73.3% accepted to participate. Information was collected using a self-administered questionnaire assessing socio-demographic, behavioural, family and health-related characteristics. The magnitude of the associations between those characteristics and physical fighting was estimated using logistic regression. Overall, 33.8% of adolescents (48.6% of boys and 20.1% of girls; p < 0.001) engaged in a physical fight during the previous 12 months. The school premises were the most frequently reported setting where fights occurred (girls--41.2% and boys--46.7%, p = 0.179). After adjustment, and in both genders, we found statistically significant associations between physical fighting and grade retention, smoking, drinking and age at first sexual intercourse. Physical fighting among school-going adolescents is frequent, tends to occur at school premises and to cluster with other well recognized adverse health behaviours.


Lymphatic drainage of the superficial tissues of the head and neck: anatomical study and clinical implications.
Current knowledge of the anatomy of the lymphatic system does not match or explain some of the unexpected clinical and lymphoscintigraphic findings seen in head and neck cancer patients. There is the need, therefore, to remap the lymphatic network of the superficial tissues of the head and neck region. Eighteen halves of the superficial tissues of the head and neck from nine fresh human cadavers were studied over a 20-month period using a mixture of 6% hydrogen peroxide (Orion Laboratories, Balcatta, Australia) with and without India ink to detect the lymphatic vessels and then inject them with a radiopaque lead oxide mixture (AJAX Chemicals, Sydney, Australia). These unique studies showed (1) lymph capillaries arising from the skin and the galea layers draining sequentially into precollecting lymph vessels, collecting lymphatics, and the first-tier lymph nodes; (2) collecting vessels averaging 0.2 mm in diameter with unusual "lymphatic ampullae" structures and inactive lymph nodes observed often along their course; (3) different network patterns between subjects and between sides of the same subject; (4) similar relationships between lymphatic and venous systems; (5) a lymphaticovenous shunt in the occipital region; (6) lymphatics sometimes bypassing the expected nodes to reach sentinel nodes in the root of the neck; and (7) the lymphatics of the anterior neck lying above the platysma and coursing horizontally, obliquely, and upward toward the mandible. A map of the head and neck lymphatics is presented to aid clinicians with the management of trauma and malignancies in the region.


Etiology, diagnosis, and prognosis of positive blood cultures.
The case records of 516 patients with 613 organisms from positive blood cultures at Detroit General Hospital (1975) and Harper-Grace Hospitals (first half of 1979) were analyzed. Gram-negative bacilli predominated by 46 per cent at Detroit General Hospital and 39 per cent at Harper-Grace Hospital. The gram-negative bacteremias also had higher mortality rates (47 per cent at Detroit General Hospital and 39 per cent at Harper-Grace Hospital) than the other organisms (27 per cent at Detroit Hospital and 25 per cent at Harper-Grace Hospital). The lung was the most frequent source for positive blood cultures at Detroit General Hospital (42%), whereas the urinary tract was the major primary site at Harper-Grace Hospital (30%). If sepsis was not diagnosed and operated upon aggressively prior to the development of shock or organ failure, the mortality rate rose from 12 per cent to 64-88 per cent. Increased efforts must be made to diagnose sepsis early and drain any collections of pus, particularly in anergic patients who may show little or no evidence of sepsis even after the development of multiple organ failure or shock.


Psychoanalytic Psychotherapy for Children and Adolescents with Severe Externalising Psychopathology: An Effectiveness Trial.
This partly waitlist-controlled prospective field study aimed to evaluate the effectiveness of psychoanalytic psychotherapy for children and adolescents with severe externalising symptoms. Externalising symptoms are associated with diagnoses of conduct disorders, hyperkinetic disorders, and disorders of social functioning. Participants were 93 children and adolescents in psychoanalytic therapy with a diagnosed psychiatric disorder with externalising symptomatology (intervention group: n = 65; minimal supportive treatment/waitlist control group: n = 28). Data was collected from parents and patients (≥ 11 years) at beginning/end of treatment, 6- and 12-month follow-up. The effects of long-term psychoanalytical treatment were analysed using a longitudinal design. At the end of therapy, externalising symptoms were significantly reduced rated by both parents and patients (parent-rated: d = .69, patient-rated: d = .63). This effect was stable at the 1-year follow-up (parent-rated: d = .77, patient-rated: d = .68). About 70% of the patients may be considered as recovered or improved by the end of therapy. Psychoanalytic therapy may be successful in alleviating psychiatric disorders with externalising symptoms with effects stable at the 1-year follow-up.


Abolition of digitalis tachyarrhythmias by caffeine.
Digitalis-induced ventricular tachyarrhythmias (VTAs) are believed to be due to oscillatory afterpotentials (OAPs) generated by an oscillatory release of calcium from the sarcoplasmic reticulum (SR). Caffeine blocks the calcium uptake into the SR and then may influence VTAs by depleting the SR stores of calcium. We studied the action of digitalis and caffeine, singly and in combination, in the isolated guinea pig heart perfused by means of a modified Langendorff apparatus. Digitalis (beta-methyldigoxin 1.27 X 10(-6) M) caused VTAs and ventricular fibrillation (VF) in all the hearts. Caffeine alone decreased heart rate but never caused VTAs. With the administration of digitalis and caffeine (1 mM), VTAs rarely developed and VF never occurs. With digitalis and higher concentration of caffeine (10 mM), neither VTAs nor VF were observed. In hearts with complete atrioventricular block, digitalis increased the ventricular rate from 143 +/- 10 to 270 +/- 13 beats/min (n = 8) in 12 +/- 1.9 min and provoked the appearance of multiple ventricular pacemakers. The addition of 10 mM caffeine to the digitalis-containing solution reduced the ventricular rate to 171 +/- 12 beats/min (P less than 0.001 vs. digitalis alone, not significant vs. control, n = 8) and abolished the digitalis-induced multiple pacemakers. Ventricular asystole was occasionally observed during the perfusion with digitalis + 10 mM caffeine. Caffeine alone did not modify the diastolic pressure, whereas caffeine and digitalis rapidly increase it. These results represent indirect evidence to support that SR plays an important role in the origin of the digitalis-induced VTAs.


Does performance on United States national board of medical examiners reflect student clinical experiences in United Arab Emirates?
This article was migrated. The article was marked as recommended. Background: A number of medical schools around the world use the United States National Board of Medical Examiners Subject Examinations as a clerkship assessment of student performance, yet these exams were blueprinted against the United States national core clerkship curriculum which might not be the same as the local curricula to which they are applied in other parts of the world. In this study, we investigated the correlations between the internal medicine clinical experiences at United Arab Emirates University with student performance on the National Board of Medical Examiners subject of internal medicine (NBME). Methods: One hundred and seven junior clerkship students out of 145 (74%) who finished their Internal Medicine clerkship during academic years 2014-2015 and 2015-2016 participated in this study. The students' clinical experiences were measured by the clinical learning evaluation questionnaire (CLEQ) and by the logged number of meaningful patient contacts during their internal medicine clerkship. Results: Linear regression analysis showed no significant association between performance on the subject test and student clinical experiences measured by the CLEQ or the number of logged patients. NBME scores were weakly correlated with OSCEs scores (ɸ 0.20). Conclusions: The study findings raised uncertainties about the suitability of using NBME in the clerkship assessment program in the United Arab Emirates.


Effect of smoking on cerebrovascular reactivity.
Current smoking is a risk factor for stroke. The aim of this study was to evaluate the effect of smoking one cigarette on cerebral hemodynamics. Using transcranial Doppler ultrasound, we studied the changes of flow velocity after hypercapnia in the middle cerebral arteries (MCAs) of 24 healthy young smokers and 24 healthy controls matched for age and sex. We obtained hypercapnia with breath-holding and evaluated cerebrovascular reactivity with the breath-holding index. In smokers, the evaluation was performed during basal condition, immediately after smoking one cigarette, and at 10-, 20-, and 30-min intervals thereafter. In controls, the evaluation was performed at corresponding time intervals. Breath-holding index (BHI) values at rest were similar for both controls and smokers. In the former, breathholding index values remained constant for each of the different evaluations. On the contrary, in smokers, breath-holding index values were significantly lower immediately (p < 0.0001), at 10 min (p < 0.001), and at 20 min (p < 0.0001) after smoking with respect to baseline values. Smoking also caused more short-lasting changes, in this case increases in mean flow velocity (MFV), heart rate (HR), and mean blood pressure (MBP). These results suggest that a failure of cerebrovascular regulation occurs after smoking. This phenomenon might contribute to the increased risk of cerebrovascular disease in current smokers.


Renal function, neurohormonal activation, and survival in patients with chronic heart failure.
Because renal function is affected by chronic heart failure (CHF) and it relates to both cardiovascular and hemodynamic properties, it should have additional prognostic value. We studied whether renal function is a predictor for mortality in advanced CHF, and we assessed its relative contribution compared with other established risk factors. In addition, we studied the relation between renal function and neurohormonal activation. The study population consisted of 1906 patients with CHF who were enrolled in a recent survival trial (Second Prospective Randomized study of Ibopamine on Mortality and Efficacy). In a subgroup of 372 patients, plasma neurohormones were determined. The baseline glomerular filtration rate (GFR(c)) was calculated using the Cockroft Gault equation. GFR(c) was the most powerful predictor of mortality; it was followed by New York Heart Association functional class and the use of angiotensin-converting enzyme inhibitors. Patients in the lowest quartile of GFR(c) values (<44 mL/min) had almost 3 times the risk of mortality (relative risk, 2. 85; P<0.001) of patients in the highest quartile (>76 mL/min). Impaired left ventricular ejection fraction (LVEF) was only modestly predictive (P=0.053). GFR(c) was inversely related with N-terminal atrial natriuretic peptide (ANP; r=-0.53) and, to a lesser extent, with ANP itself (r=-0.35; both P<0.001). Impaired renal function (GFR(c)) is a stronger predictor of mortality than impaired cardiac function (LVEF and New York Heart Association class) in advanced CHF, and it is associated with increased levels of N-terminal ANP. Moreover, impaired renal function was not related to LVEF, which suggests that factors other than reduced cardiac output are causally involved.


Regulation of ATP-dependent surfactant secretion and activation of second-messenger systems in alveolar type II cells.
Several different classes of agonists are known to stimulate exocytosis in type II cells. These agonists cause increases in second messengers, such as adenosine 3',5'-cyclic monophosphate (cAMP) or cytosolic Ca2+, and/or stimulate protein kinase C. We studied generation of cAMP and phosphoinositide (PI) turnover in monolayer cultures of type II cells and measured [Ca2+]i in single cultured cells. ATP [10(-4) M], which stimulates secretion of phosphatidylcholine (PC) and increases cellular cAMP, also stimulated PI turnover and increased [Ca2+]i. 12-O-tetradecanoylphorbol-13-acetate (TPA), which stimulates PC secretion and activates protein kinase C, did not increase [Ca2+]i. Pretreatment of type II cells with the calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) inhibited the PC secretion induced by ATP and TPA and blocked the increase in PI turnover caused by ATP. ATP-dependent surfactant secretion and stimulation of PI turnover could also be inhibited by pretreatment of the cells with pertussis toxin. We used the fluorescent probe indo-1 to measure [Ca2+]i in single cultured type II cells. ATP produced rapid transient increases in [Ca2+]i, which could be prevented by pretreatment of the cells with either TPA or W-7. Our data suggest that pertussis toxin-sensitive G protein(s) are involved in ATP-dependent activation of PI turnover and in secretion of surfactant in type II cells. Activation of protein kinase C blocks the ATP-stimulated increase in [Ca2+]i. Finally, calmodulin may be involved in the regulation of ATP-dependent increase in [Ca2+]i, the activation of PI turnover, and the secretion of surfactant in type II cells.


Physical exercise for people with cirrhosis.
Loss of muscle mass and muscle weakness are common complications to cirrhosis and are associated with increased morbidity and mortality. Therefore, physical exercise may benefit people with cirrhosis. To assess the beneficial and harmful effects of physical exercise versus sham exercise or no exercise for people with cirrhosis. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Embase Ovid, and three other databases, including manual searches through reference lists, abstracts, and presentations at conferences and meetings, Google Scholar, and online trial registers in February 2018. We included randomised clinical trials regardless of publication status or language. Inclusion criteria were cirrhosis irrespective of the aetiology or stage. Interventions were physical exercise compared with sham exercise or no intervention. Three review authors independently extracted data. We undertook meta-analyses and presented results using risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, both with 95% confidence intervals (CI) and I2 values as markers of imprecision and heterogeneity. We assessed bias control using the Cochrane Hepato-Biliary Group domains and determined the credibility of the evidence using GRADE. We included six randomised clinical trials with 173 participants. All participants had Child-Pugh stage A or B cirrhosis. The intervention groups participated in eight to 14 weeks of physical exercise (aerobic: three trials; resistance: one trial; or aerobic plus resistance training: two trials). Control groups underwent sham exercise (supervised relaxation: one trial) or no intervention (five trials). None of the 89 participants allocated to exercise versus two of 84 participants in the control group died (RR 0.19, 95% CI 0.01 to 3.73; moderate-quality evidence). The cause of death was acute-on-chronic liver disease for both participants. Nine participants in the exercise group and 13 in the control group experienced serious adverse events (RR 0.61, 95% CI 0.19 to 1.94; low-quality evidence).Physical exercise showed no beneficial or detrimental effect on health-related quality of life assessed by the Chronic Liver Disease Questionnaire (MD 0.11, 95% CI -0.44 to 0.67; low-quality evidence). Likewise, physical exercise had no clear effect on physical fitness measured by peak exercise oxygen uptake (MD 0.3 mL/kg/minute, 95 % CI -2.74 to 3.35; low-quality evidence) and Six-Minute Walk Test (MD 56.06 min, 95% CI -9.14 to 121.26; very low-quality evidence). Physical exercise showed no clear effect on mid-thigh circumference (MD 1.76 cm, 95% CI -0.26 to 3.77; low-quality evidence), but showed an increase in mid-arm circumference (MD 2.61 cm, 95% CI 0.36 to 4.85; low-quality evidence). We found no clear beneficial or harmful effect of physical exercise on mortality, morbidity, or health-related quality of life. Further evidence is needed to evaluate the beneficial and harmful effects of physical exercise on clinical outcomes.


Investigate the relation between Adiponectin gene variants and cardiovascular comorbidities and diabetes.
This study aimed to study the relationship between the adiponectin gene and coronary artery disease as well as myocardial infarction, hypertension and diabetes in the Saudi population in Riyadh. This was a cohort study of Saudi patients from the Coronary Artery Disease (CAD) registry maintained at King Faisal Specialist Hospital and Research Centre. Samples were genotyped for target Single Nucleotide Polymorphisms (SNPs) by real time polymerase chain reaction (PCR). Furthermore, Chi Square test was used for comparing the variables. Out of 860 CAD patients compared with 467 non-CAD. The prevalence of the minor G allele of +45T>G in CAD patients was 934 compared to 786 in controls, and it shows no significant difference (p=0.598) between the two groups. The possibility tested that this variant might be associated with one or more of the CAD risk factors, such as hypertension, myocardial infarction, hypertension and diabetes mellitus. Nevertheless, the study did not show any significance between the two groups in CAD, gender and hypertension. On the other hand, the difference in MI was borderline and significant in diabetes mellitus. This study showed a relationship between adiponectin and diabetes only as compared to results from other countries which also showed relationship with coronary artery disease, myocardial infarction and hypertension.


Phorbol ester-induced lymphocyte adherence: selective action on NK cells.
Treatment of human peripheral blood lymphocytes (PBL) with phorbol dibutyrate (PDBU) for 20 to 45 min at 37 degrees C induces adherence of 5 to 30% of the cells to plastic. The adherent cells (pAd) were highly enriched in NK cells on the basis of the following findings: 1) they exhibit high NK and ADCC activity but do not lyse the NK-resistant cell line, Daudi; 2) cytotoxic activity is enhanced by pretreatment with interferon-alpha (IFN-alpha); 3) the surface markers of these cells, as determined with monoclonal antibodies, are consistent with NK cells; and 4) they are enriched with cells morphologically similar to large granular lymphocytes. Conversely, the PDBU-nonadherent cells were substantially depleted of NK cells. The fact that the pAd cells do not lyse the Daudi line and that their NK activity can be further augmented by IFN-alpha would suggest that the pAd are enriched for NK cells rather than changed in their characteristics as a result of the separation procedure. Moreover, no consistent and appreciable modulation of NK activity induced by PDBU was observed. This report therefore demonstrates that PDBU selectively induces NK adherence of NK cells, which may have practical as well as biological implications.


Selectivity and potential interference from phenolic compounds in chemiluminescence methods for the determination of synephrine.
Three recently reported chemiluminescence methods (based on reactions with alkaline luminol and hexacyanoferrate(III); acidic cerium(IV) and rhodamine B; and acidic permanganate with polyphosphates) for the determination of synephrine were re-evaluated in terms of their selectivity towards this analyte in comparison to other phenolic compounds. A fourth reagent system, acidic soluble manganese(IV) and formaldehyde, was also examined. Each set of reagents was sensitive towards synephrine (limits of detection were 3 x 10(-9), 5 x 10(-8), 1 x 10(-8) and 1 x 10(-8) mol/L, respectively) but also responded with numerous other phenolic compounds, including some that are present in citrus fruit extracts, dietary supplements and/or biological fluids. It is therefore recommended that the determination of synephrine in these matrices should incorporate physical separation of sample components (e.g. chromatography or electrophoresis). In more general terms, this study illustrates that accurate percentage recoveries for an analyte in spiked samples (without validation against another analytical method) are insufficient to confirm the analytical utility of new flow-injection analysis (FIA) procedures.


Retrospective analysis of antihypertensive drug therapy using various pharmacokinetic and pharmacodynamic methods.
A retrospective analysis of blood pressure data from 42 published studies representing 23 different drug regimens and 971 patients was used to test various pharmacokinetic and pharmacodynamic methods for analyzing the effectiveness of antihypertensive drug therapy. The methods assume that a plot of the drug-induced decrement in diastolic pressure versus the pretreatment diastolic pressure yields an "ideal response line" that has a slope of 1.0 and an intercept on the pretreatment axis, representing the therapeutic endpoint of 90 mm Hg. The plot was used to test the congruence of each regimen with the "ideal" relationship, the percent of patient responses to each regimen that were successful in achieving the therapeutic endpoint, and the mean performance values for each regimen. The results obtained suggest that what is the ideal response in theory is not observed in practice. Six regimens showed no statistically significant difference between the calculated regression line and the ideal regression line. Seven regimens demonstrated overall success rates of 67% or greater in reducing pretreatment diastolic pressure to 90 mm Hg. Only one regimen--reserpine, hydralazine, plus hydrochlorothiazide--achieved combined performance factors of r2 greater than or equal to 0.67 and a success rate greater than or equal to 67%. Although interpatient variation in response is observed with all treatments studied, some regimens were markedly more effective and predictable than others in reducing diastolic pressure to the desired treatment endpoint.


In situ identification of mycobacteria in Crohn's disease patient tissue using confocal scanning laser microscopy.
The diversity in the methodology employed to investigate Crohn's disease (CD) etiology has added significantly to the controversy of the mycobacterial role in this chronic inflammatory bowel disease. Mycobacterium avium subsp paratuberculosis (MAP), a proposed and suspected agent in many CD patients, is a fastidious and very slow grower bacillus, which causes Johne's disease (JD) in cattle. The methodology that has been widely and successfully used for isolation and identification of MAP from and in JD animals is not reliable and has proven to be unsuccessful in achieving the same objectives for CD diagnosis. In this study, a Confocal Scanning Laser Microscopy (CSLM) system has been employed in an attempt to detect MAP in CD patient. In situ hybridization was performed on full thickness tissue using rabbit anti-MAP polyclonal antibody that was adsorbed with E. coli protein extracts. Consequently, MAP was detected in the microvilli region in tissue specimens from CD patient and not in the controls. In the same CD tissue specimen, MAP was not detected when isotype normal rabbit sera was employed. The polyclonal antibody marker may be replaced with monoclonal antibodies, if available, or with MAP-specific-DNA or RNA probes. This technique adds an additional approach to investigate MAP role in CD etiology especially when the culture approach is long and inconsistent.


Selective processing of vestibular reafference during self-generated head motion.
The vestibular sensory apparatus and associated vestibular nuclei are generally thought to encode head-in-space motion. Angular head-in-space velocity is detected by vestibular hair cells that are located within the semicircular canals of the inner ear. In turn, the afferent fibers of the vestibular nerve project to neurons in the vestibular nuclei, which, in head-restrained animals, similarly encode head-in-space velocity during passive whole-body rotation. However, during the active head-on-body movements made to generate orienting gaze shifts, neurons in the vestibular nuclei do not reliably encode head-in-space motion. The mechanism that underlies this differential processing of vestibular information is not known. To address this issue, we studied vestibular nuclei neural responses during passive head rotations and during a variety of tasks in which alert rhesus monkeys voluntarily moved their heads relative to space. Neurons similarly encoded head-in-space velocity during passive rotations of the head relative to the body and during passive rotations of the head and body together in space. During all movements that were generated by activation of the neck musculature (voluntary head-on-body movements), neurons were poorly modulated. In contrast, during a task in which each monkey actively "drove" its head and body together in space by rotating a steering wheel with its arm, neurons reliably encoded head-in-space motion. Our results suggest that, during active head-on-body motion, an efferent copy of the neck motor command, rather than the monkey's knowledge of its self-generated head-in-space motion or neck proprioceptive information, gates the differential processing of vestibular information at the level of the vestibular nuclei.


Study of cutaneous leishmaniasis in the State of Campeche (Yucatan Peninsula), Mexico, over a period of two years.
To study cutaneous leishmaniasis (CL), in the Calakmul municipality of the Campeche State, during two years. Individuals with skin lesions were evaluated. Aspirates taken from the lesions were cultured, PCR was performed to diagnose the Leishmania species. The culture detected 42% of the samples. PCR diagnosed CL in 76% of the samples; of those 38% were from children and 62% from adults. 89% of the patients were infected with L. mexicana; 14.4% with Mexican strains of L. mexicana; 7% with L. braziliensis; 3.6% with L. mexicana and L. braziliensis. The most affected villages with CL were Dos Lagunas Sur with 12.3%, La Mancolona with 6.5% and La Guadalupe with 2.2% of prevalence, respectively. After the treatment with Glucantime, 96% of the patients were healed. CL is an important public health concern in Calakmul, and the parasite causing it belongs to Leishmania mexicana and Leishmania braziliensis complexes.


Effects of spray-dried porcine plasma on growth performance, immune response, total antioxidant capacity, and gut morphology of nursery pigs.
Two experiments were conducted to evaluate the effects of spray-dried porcine plasma (SDPP) on growth performance, immunity, antioxidant capacity, and gut morphology of nursery pigs. In Exp. 1, 96 weaned pigs (Nebraska female × Danbred sire; 20 ± 1 d of age; initial BW = 6.06 ± 0.02 kg) were assigned to 16 pens and randomly allotted to the control (CTL; no SDPP) or the CTL + SDPP treatment in 2 phases (phase 1: d 0 to 14, 5% SDPP; phase 2: d 14 to 28, 2.5% SDPP). Blood samples were collected on d 0 and weekly thereafter to quantify IgG, IgA, and total antioxidant capacity. On d 14, pigs (n = 16; 8 pigs/treatment) were selected and euthanized for small intestine tissue and alveolar macrophage collection. On d 7, pigs fed SDPP had greater ADG, ADFI (P = 0.001), and G:F (P = 0.019) compared with CTL pigs. On d 28, pigs fed SDPP had greater BW (P = 0.024) and tended to have greater ADG (P = 0.074) and ADFI (P = 0.062) compared with CTL pigs. There were no differences between treatments for serum IgG, IgA, and total antioxidant capacity. On d 14, greater villus height (P = 0.011) and villus:crypt (P = 0.008) were observed in duodenal tissue sections obtained from SDPP-fed pigs compared with CTL pigs. To evaluate effects of SDPP on immune biomarkers, alveolar macrophages collected from 3 pigs/treatment on d 14 were cultured in vitro and challenged with lipopolysaccharide (LPS; 10 ng/mL). Therefore, 4 treatments included 1) CTL diet with no LPS, 2) CTL diet with LPS (CTL+), 3) SDPP diet with no LPS, and 4) SDPP diet with LPS. There were no diet effects on tumor necrosis factor-α gene expression or secretion by alveolar macrophages. For IL-10 gene expression, a diet × LPS interaction (P = 0.009) was observed where CTL+ had greater (P < 0.05) IL-10 mRNA abundance compared with other treatments. A second experiment was conducted to evaluate the in vitro effects of porcine plasma using model porcine jejunal epithelial cells (IPEC-J2). The treatments applied to the IPEC-J2 cells were 1) CTL, 2) CTL + 10% porcine plasma, 3) CTL + 5% porcine plasma, 4) CTL + 2.5% porcine plasma, or 5) CTL + 5% fetal bovine serum. The addition of porcine plasma increased (P < 0.001) proliferation of IPEC-J2 cells at 24 and 48 h following exposure to the respective treatments. In conclusion, dietary SDPP increased growth performance of nursery pigs during the first week postweaning and provide benefits to gut morphology possibly via increased proliferation of enterocytes.


Conversion of a scorpion toxin agonist into an antagonist highlights an acidic residue involved in voltage sensor trapping during activation of neuronal Na+ channels.
Gating modifiers constitute a large group of polypeptide toxins that interact with the voltage-sensing module of ion channels. Among them, scorpion beta-toxins induce a negative shift in the voltage dependence of sodium channel activation. To explain their effect, a "voltage sensor trapping" model has been proposed in which the voltage sensor of domain-II (DIIS4) is trapped in an outward, activated position by a prebound beta-toxin upon membrane depolarization. Whereas toxin effect on channel activation was enhanced upon neutralization of the two outermost arginines in DIIS4, toxin residues involved in sensor trapping have not been identified. Using the scorpion excitatory beta-toxin, Bj-xtrIT, we found two conserved acidic residues, Glu15 and Glu30, mandatory for toxin action. Whereas mutagenesis of Glu30 affected both toxicity and binding affinity, substitutions E15A/F abolished activity but had minor effects on binding. Complete uncoupling of activity from binding was obtained with mutant E15R, acting as an efficient antagonist of Bj-xtrIT. On the basis of the voltage sensor trapping model and our results, we propose that Glu15 interacts with the emerging gating charges of DIIS4 upon membrane depolarization. Conserved acidic residues found in a variety of gating modifiers from scorpions and spiders may interact similarly with the voltage sensor.


Water absorption in the proximal tubule: effect of bicarbonate, chloride gradient, and organic solutes.
Simultaneous in vivo capillary and luminal microperfusion studies were performed in the superficial proximal convoluted tubule of the rat to determine the effect of intraluminal bicarbonate, the imposition of a transepithelial chloride gradient, and the addition of organic solutes to the luminal perfusion solution on the rates of water absorption (Jv). The capillary perfusion solution contained NaCl, NaHCO3, and KCl. Perfusion of both capillary and lumen with the same solution resulted in a Jv of 3.01 +/- 0.24 nl/min/mm. Imposition of a transepithelial chloride gradient (equimolar substitution of NaCl for NaHCO3 in the luminal solution) resulted in a Jv of 3.18 +/- 0.21 nl/min/mm (P = NS). Addition of cyanide to both solutions in the presence of a chloride gradient resulted in a significantly lower Jv of 2.21 +/- 0.19 nl/min/mm. Luminal substitution of Na cyclamate for NaHCO3 resulted in a solution containing no bicarbonate and no chloride gradient. Jv averaged 0.34 +/- 0.08 nl/min/mm. Addition of cyanide to the solution totally inhibited Jv. The addition of D-glucose, L-alanine, or both, to luminal solutions containing bicarbonate or in the presence of a chloride gradient did not significantly affect Jv. Addition of both organic solutes to the NaCl-Na cyclamate luminal solution resulted in a significantly higher Jv of 0.77 +/- 0.14 nl/min/mm. These studies indicate that Jv in the rat superficial proximal tubule is influenced by active sodium transport, by the presence of bicarbonate in the lumen, and/or by the imposition of a transepithelial chloride gradient. The organic solutes D-glucose and L-alanine also influence water absorption, but this effect could only be demonstrated under some experimental conditions.


Dorsal transfer of the brachioradialis to the flexor pollicis longus enables simultaneous powering of key pinch and forearm pronation.
To show biomechanically that the brachioradialis (BR) muscle can be transferred to restore key pinch and forearm pronation simultaneously. Nine fresh-frozen forearms were thawed and instrumented with a custom muscle-tendon excursion jig. Maximum BR muscle-tendon excursion was measured with the wrist and thumb mobile. Muscle-tendon excursion then was measured from 60 degrees of supination to 60 degrees of pronation in 15 degrees increments with the wrist and thumb fixed. Measurements were performed in 3 configurations: the native BR, the BR transferred volarly to the flexor pollicis longus (FPL) tendon, and the BR transferred dorsally (posterior to the radius) through the interosseous membrane to the FPL tendon. Muscle excursion-joint angle data were differentiated to compute pronation/supination moment arms. Two-way analyses of variance and post hoc Tukey tests were used to compare transfer conditions. Maximum muscle excursion was nearly identical when volar and dorsal transfer conditions were compared. When pronation/supination motions were isolated, however, the volar transfer was associated with muscle shortening and small pronation moment arms through 30 degrees +/- 9 degrees of supination. Importantly, the dorsal transfer was associated with muscle shortening and larger pronation moment arms through 28 degrees +/- 10 degrees of pronation, a significant difference of 58.0 degrees +/- 16.0 degrees compared to the traditional volar transfer. These data suggest that dorsal BR-to-FPL transfers can power key pinch and forearm pronation simultaneously even in the absence of other functional pronators. This transfer can be accomplished without changes to total muscle excursion compared with the traditional volar BR-to-FPL transfer. This result may enable the use of the BR-to-FPL transfer in patients who need key pinch but who lack functional pronation muscle groups (eg, ocular cutaneous 3). As result a larger patient population may benefit from the BR-to-FPL reconstructive procedure.


[Risks and resources for mental health of children and adolescents].
Children's and adolescents' mental health is an epidemiological outcome of considerable public health relevance. This is based on a comparably high prevalence of mental health problems and disorders in children and adolescents. The supplementary study 'Mental Health', which is a modular part of the Health Survey for Children and Adolescents conducted by the Robert Koch Institute, aims at assessing the prevalence of specific mental health problems and disorders in a representative sample of children and adolescents in Germany. Furthermore, determinants of mental health will be studied in a developmental context. Screening to assess mental health problems will be performed in a representative sub-sample of the National Health Survey for Children and Adolescents. The sub-sample will comprise approximately 4,000 children and adolescents aged 7 to 17 years. Participants are interviewed once to assess the occurrence of risk factors and available assets (protective factors) for mental health, thus providing valuable data for health monitoring and planning (cross-sectional part of the study). A sub-group of this cross-sectional sample as well as an additional clinical sample are repeatedly studied in a longitudinal design. This part of the study is carried out to estimate the effect size of risk and protective factors on mental health, and to analyse their combined effects on the developmental process. From the findings, clues to effective prevention and intervention strategies can be derived.


[Establishment of a new human endometrial adenocarcinoma cell line, Ishikawa cells, containing estrogen and progesterone receptors].
A new human endometrial adenocarcinoma cell line, Ishikawa cells, was established from an endometrial adenocarcinoma from a 39-year-old woman and has been maintained in vitro for more than 3 years. The cells were found to form a monolayer in a mosaic fashion and to tend to pile up. Population doubling time was calculated to be about 36, 29 and 27 hours at the 9th, 40th and 50th generations, respectively. The modal chromosomal number of the cells fell in a diploid range. Histology of the tumor induced in athymic nude mice showed it to be a well differentiated adenocarcinoma which closely resembled the original human tumor. Estrogen receptor and progesterone receptor were demonstrated to occur not only in the induced tumor in athymic nude mice but also in in vitro culture cells. From the fact that the cell growth was maintained in an estrogen-free medium, it appeared that the cells had no estrogen dependency.


Elimination of Simulium neavei-Transmitted Onchocerciasis in Wambabya-Rwamarongo Focus of Western Uganda.
Wambabya-Rwamarongo onchocerciasis focus is one of the eight foci Uganda verified using the WHO verification guidelines. The approach for elimination was twice yearly treatment with ivermectin for every round, treating at least 90% of all the eligible population. This was in combination with vector elimination using Abate® (BASF SE, Limburgerhof, Germany) since elimination nationwide policy was launched. From 2008 to 2013, the program distributed ivermectin with a mean treatment coverage of the ultimate treatment goal (UTG) or eligible population of 91.2%, with a range of 85-96%. In 2009, vector elimination based on ground larviciding had a dramatic impact on the Simulium vectors, as the last fly was observed in October 2009. No more Simulium vectors were observed during a period of at least 7 years, including the 3-year posttreatment surveillance (PTS) until the focus was reclassified as eliminated in August 2017. During the PTS period, none of the 10,578 trapped crabs were found infested with the aquatic stages of the vector. The last infested crab was observed in March 2010, and for at least 7 years, no infested crabs were observed. Serological surveys showed that of 2,978 young children examined in 2013, only one was OV16 positive (0.0%; 95% CI: 0-0.21). In 2017, after the PTS period, all 3,079 young children examined were negative for OV16 (95% CI: 0-0.16). Therefore, entomological and serological results provided evidence that resulted in the reclassification of Wambabya-Rwamarongo focus from "transmission interrupted" to "transmission eliminated" with no possibility of recrudescence.


Aspects of tests and assessment of filtering materials used for respiratory protection against bioaerosols. Part II: sweat in the environment, microorganisms in the form of a bioaerosol.
The second part of the article presents the results of a study of antimicrobial activity of filter nonwovens with an addition of biocides, as a function of the presence of sweat in the environment and the method of microbe deposition on a nonwoven in the form of a liquid and a bioaerosol. At the same time, the filtration efficiency of nonwovens against microorganisms in the form of a bioaerosol was tested with the dynamic method. The results showed that the addition of sweat on the surface of a nonwoven resulted in an insignificant decrease of biological activity that still remained high. Moreover, an active nonwoven showed biostatic and biocidal activity only when microbes were deposited on the surface in the form of a solution. The nonwoven did not show any biological activity after deposition of microorganisms with the dynamical method in the form of a bioaerosol.


Correlates of social problem solving during the first year after traumatic brain injury in children.
Effects of pediatric traumatic brain injury (TBI) on social problem-solving were examined in a longitudinal study of 103 children with moderate-to-severe TBI (n = 52) or orthopedic injury (OI; n = 51) using the Interpersonal Negotiation Strategies task (INS). Children solved age-appropriate hypothetical social conflicts, with responses for four problem-solving steps scored by developmental level. The OI group performed better than the TBI group, but rate of change in performance over time did not differ between groups, suggesting improvement in children with TBI was not due to recovery from injury. Strong relations between INS performance and memory and language skills emerged, but emotional processing was only weakly related to INS performance. Frontal focal lesions influenced INS performance in younger (but not older) children with TBI. Diffusion tensor imaging (DTI), revealed strong relationships between the INS and increased apparent diffusion coefficient (ADC) measures indexing connectivity in the dorsolateral and cingulate regions in both TBI and OI groups, and in the temporal and parietal regions in the TBI group. These findings inform studies of social problem-solving skills during the first year post TBI. (PsycINFO Database Record (c) 2008 APA, all rights reserved).


Miliary tuberculosis in a young Caucasian adult.
A young Caucasian adult presented to the Accident and Emergency department with small bowel obstruction, which necessitated an exploratory laparotomy. Multiple firm nodules were found with biopsies leading to a diagnosis of peritoneal tuberculosis (TB). Retrospectively, the patient was noted to have classical radiological pulmonary TB findings on a chest radiograph 3 months previously, and 2 weeks later had developed bony infiltration, paravertebral abscesses and likely TB skin lesions. This case illustrates an unusual presentation in a patient with minimal risk factors yet widespread extra-pulmonary disease. It also highlights the importance of attentive reviewing of x-rays.


Suspected Synthetic Cannabinomimetic Intoxication: Case Series and Review.
The purpose of this work was to retrospectively review patient cases presenting to the University of Kentucky Chandler Medical Center (UKCMC) emergency department (ED) with symptoms of suspected synthetic cannabinomimetic (SC) intoxication. These drugs, currently undetected by standard urine drug screen tests, comprise a structurally diverse group of compounds designed to mimic the psychoactive effects of Δ9-tetrahydrocannabinol (Δ9-THC), the primary psychoactive cannabinoid in marijuana. Fourteen cases of suspected SC intoxication were identified between July 1, 2015, through September 30, 2015. The median patient age was 25.5 years (range: 13-45 years), and most (64%) patients were males. The most common psychoactive symptom was agitation (n = 6, 42.9%), while the most common physical symptoms were altered level of consciousness (n = 9, 64.3%) and mydriasis (n = 3, 21.4%). Most cases resolved without complication in 24 hours; 2 patients required hospitalization. Recent legislation has failed to curb the public health concerns emanating from SC misuse. Education about the risks of SC use along with additional regulation may be required to remove the false sense of safety that some individuals, especially adolescents and young adults, may associate with these compounds, which are often misconstrued as "herbal marijuana." Clinicians need to be prepared to identify and treat symptoms of SC intoxication as incidents of toxicity continue to rise.


Modulation of the expression of mimivirus-encoded translation-related genes in response to nutrient availability during Acanthamoeba castellanii infection.
The complexity of giant virus genomes is intriguing, especially the presence of genes encoding components of the protein translation machinery such as transfer RNAs and aminoacyl-tRNA-synthetases; these features are uncommon among other viruses. Although orthologs of these genes are codified by their hosts, one can hypothesize that having these translation-related genes might represent a gain of fitness during infection. Therefore, the aim of this study was to evaluate the expression of translation-related genes by mimivirus during infection of Acanthamoeba castellanii under different nutritional conditions. In silico analysis of amino acid usage revealed remarkable differences between the mimivirus isolates and the A. castellanii host. Relative expression analysis by quantitative PCR revealed that mimivirus was able to modulate the expression of eight viral translation-related genes according to the amoebal growth condition, with a higher induction of gene expression under starvation. Some mimivirus isolates presented differences in translation-related gene expression; notably, polymorphisms in the promoter regions correlated with these differences. Two mimivirus isolates did not encode the tryptophanyl-tRNA in their genomes, which may be linked with low conservation pressure based on amino acid usage analysis. Taken together, our data suggest that mimivirus can modulate the expression of translation-related genes in response to nutrient availability in the host cell, allowing the mimivirus to adapt to different hosts growing under different nutritional conditions.


Variation in mitochondrial translation products associated with male-sterile cytoplasms in maize.
Mitochondria were isolated under sterile conditions from maize lines with normal cytoplasm and with T, C, and S sources of cytoplasmic male sterility. Protein synthesis by these mitochondria was dependent upon the presence of ADP and an oxidizable substrate or an energy generating system and displayed characteristic sensitivity towards inhibitors of protein synthesis. Approximately 20 polypeptides were detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis of the [(35)S]methionine-labeled mitochondrial translation products. Mitochondria from the T and C cytoplasms were characterized by the synthesis of a single additional or variant polypeptide.These observations are discussed with reference to the possible mechanisms of male sterility and the susceptibility of plants with T cytoplasm to Helminthosporium maydis, race T. Our results also suggest a potentially rapid method of classifying sources of cytoplasmic male sterility that could be used in conjunction with existing methods, which depend on patterns of fertility restoration after an extended breeding program.


The Efficacy of Gabapentin in Patients with Central Post-stroke Pain.
Thalamic pain syndrome, a type of central post-stroke pain (CPSP), may develops after a hemorrhagic or ischemic stroke and results in impairment of the thalamus. There is limited experience about gabapentin in treatment of central pains like CPSP. In a prospective observational study, the intensity of pain was recorded using the Numeric Rating Scale (NRS) at the entrance to the study. Patients eligible for treating with gabapentin, received gabapentin 300 mg twice-daily. The pain intensity was measured at entrance to the study and after one month using NRS. Decrease of 3 points from the initial NRS considered being clinically significant. From a total of 180 primarily screened patients, 84 (44 men and 40 women) were recruited. There was a significant difference between pre-treatment and post-treatment NRS (5.9 ± 2.51 vs. 4.7 ± 3.01; 95% CI: 0.442-1.962, p = 0.002). Fisher's exact test showed no statistically significant effect of clinical and demographic characteristics of patients on their therapeutic response to gabapentin. Given the safety, efficacy, well tolerability and lack of interaction with other drugs we suggest gabapentin to be more considered as a first line therapy or as add-on therapy for reducing the pain severity in patients with thalamic syndrome.


Alternative methods for testing treatment effects on the basis of multiple outcomes: simulation and case study.
In clinical trials multiple outcomes are often used to assess treatment interventions. This paper presents an evaluation of likelihood-based methods for jointly testing treatment effects in clinical trials with multiple continuous outcomes. Specifically, we compare the power of joint tests of treatment effects obtained from joint models for the multiple outcomes with univariate tests based on modeling the outcomes separately. We also consider the power and bias of tests when data are missing, a common feature of many trials, especially in psychiatry. Our results suggest that joint tests capitalize on the correlation of multiple outcomes and are more powerful than standard univariate methods, especially when outcomes are missing completely at random. When outcomes are missing at random, test procedures based on correctly specified joint models are unbiased, while standard univariate procedures are not. Results of a simulation study are reported, and the methods are illustrated in an example from the Clinical Antipsychotic Trials of Intervention Effectiveness for schizophrenia.


Publishing in physical and rehabilitation medicine.
This article presents the panel discussion from the "Meet the Editor" symposium held at the 4th World Congress of the International Society of Physical and Rehabilitation Medicine in Seoul in June 2006. It includes contributions by four Editors of international journals in rehabilitation. Some of the topics discussed are of a general nature but will provide useful guidance for the more junior scientific author. Some specific information about the four journals is also presented. Topics discussed include the reasons for publishing in peer-reviewed journals, important considerations in submitting a manuscript, the peer-review process, the effect of electronic publishing (which leads to shorter publication times and the opportunity to preview articles), and the trend toward more open access to journals. The discussion concludes that the field of physical and rehabilitation medicine will continue to expand, with an audience with a broader range of scientific and clinical interests. The International Classification of Functioning, Disability and Health (ICF) may be increasingly used as a framework in reporting. New journals may be started, particularly in regions of the world other than Europe and the United States, despite the fact that journals currently published in these regions are distributed worldwide.


Decreased interstitial cells of Cajal in the sigmoid colon of patients with slow transit constipation.
Slow transit constipation (STC) is a colonic motor disorder that is characterized by measurably delayed movement of materials through the colon. Although abnormalities in the neuronal networks of the colon have been demonstrated in patients with STC, the etiology of STC remains unclear. Interstitial cells of Cajal (ICC) have been shown to be the pacemaker cells of the intestine and have been implied in the pathogenesis of a number of gastrointestinal motility dysfunctions, including idiopathic STC. This study aimed to determine the normal distribution of ICC within the colon of the Chinese and also to determine if ICC are decreased in Chinese STC patients. Twelve patients with STC and eight age-matched normal controls were studied. Specimens of sigmoid colon were obtained immediately after resection. ICC were identified with a monoclonal antibody to c-kit by an indirect immunofluorescence method. Immunostained tissues were examined with a laser scanning confocal microscope and the area occupied by ICC was calculated with an image analysis system. ICC were located in the external muscle layers including myenteric plexus (MP) and submucosal border (SMB). Two types of Kit-positive ICC were observed: bipolar cells characterized by one or two long processes and multipolar cells characterized by long stellate processes extending in various directions. A higher percentage of ICC was present in the MP regions and circular muscle (CM) layers compared with the SMB and longitudinal muscle (LM) layers. Tissues from STC patients showed a considerable decrease in the number of ICC located in the four regions (ICC-LM, ICC-MP, ICC-CM, ICC-SMB), especially the ICC-SMB, in which ICC almost completely disappeared. Similar distribution of ICC was observed in the normal sigmoid colon of the Chinese. Decreased area of c-kit+ ICC may play an important role in the pathophysiology of STC. It remains to be determined whether the loss of ICC is primary or secondary to another lesion.


Blood-brain barrier modeling with co-cultured neural progenitor cell-derived astrocytes and neurons.
In vitro blood-brain barrier (BBB) models often consist of brain microvascular endothelial cells (BMECs) that are co-cultured with other cells of the neurovascular unit, such as astrocytes and neurons, to enhance BBB properties. Obtaining primary astrocytes and neurons for co-culture models can be laborious, while yield and heterogeneity of primary isolations can also be limiting. Neural progenitor cells (NPCs), because of their self-renewal capacity and ability to reproducibly differentiate into tunable mixtures of neurons and astrocytes, represent a facile, readily scalable alternative. To this end, differentiated rat NPCs were co-cultured with rat BMECs and shown to induce BBB properties such as elevated trans-endothelial electrical resistance, improved tight junction continuity, polarized p-glycoprotein efflux, and low passive permeability at levels indistinguishable from those induced by primary rat astrocyte co-culture. An NPC differentiation time of 12 days, with the presence of 10% fetal bovine serum, was found to be crucial for generating NPC-derived progeny capable of inducing the optimal response. This approach could also be extended to human NPC-derived astrocytes and neurons which similarly regulated BBB induction. The distribution of rat or human NPC-derived progeny under these conditions was found to be a roughly 3 : 1 mixture of astrocytes to neurons with varying degrees of cellular maturity. BMEC gene expression analysis was conducted using a BBB gene panel, and it was determined that 23 of 26 genes were similarly regulated by either differentiated rat NPC or rat astrocyte co-culture while three genes were differentially altered by the rat NPC-derived progeny. Taken together, these results demonstrate that NPCs are an attractive alternative to primary neural cells for use in BBB co-culture models.


Modification of the existing maximum residue levels for mancozeb in various crops.
In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Indofil Industries Limited submitted a request to the competent national authority in Germany to modify the existing maximum residue levels (MRLs) for the active substance mancozeb in garlic, broccoli, cauliflowers and leeks. The data submitted in support of the request were found to be sufficient to derive MRL proposals for the crops under consideration. Based on the risk assessment results, EFSA derived recommendations for further consideration by the risk managers. Adequate analytical methods for enforcement are available to control the residues of mancozeb in the crops under consideration.


Development and validation of an HPLC method for determination of rofecoxib in bovine serum albumin microspheres.
A simple and reliable HPLC method was developed and validated for determination of rofecoxib in bovine serum albumin microsphere. The analyses were performed on a C18 column (150 x 4.6 mm, 5 μm particle size) at room temperature with UV detection at 272 nm. The mobile phase was composed of acetonitrile-0.1% o-phosphoric acid solution in water (1:1, v/v) mixture, and flow rate was set to 1 mL/min. The method was validated according to the international guidelines with respect to stability, linearity range, limit of quantitation and detection, precision, accuracy, specificity, and robustness. The detection and quantification limit of the method were 1.0 μg/mL and 2.5 μg/mL, respectively. The method was linear in the range of 2.5-25 μg/mL with excellent determination coefficients (R2 >0.99). Intra-day and inter-day precision (<1.76% RSD) and accuracy (<0.55 % Bias) values of the method also fulfilled the required limits. It was concluded that the developed method was accurate, sensitive, precise, and reproducible according to the evaluation of the validation parameters. The applicability of the method was confirmed for in vitro quantification of rofecoxib in bovine serum albumin microspheres.


Ketone transformation as a pathway to inherently chiral rigidified calix[4]arenes.
The preparation of inherently chiral rigidified calix[4]arenes with an intact cavity is a synthetic challenge due to the complicated synthesis of the starting compounds. Here, we report on a novel strategy for bridging the upper rim of calix[4]arenes consisting in carbonyl group formation and subsequent "extension" into a two-atom bridge using corresponding rearrangement reactions (Baeyer-Villiger, Beckmann). The resulting inherently chiral compounds are potentially applicable in the design of novel receptors. The complexation properties towards selected quaternary ammonium salts were studied by 1H NMR titration. Unusual complexation stoichiometries can be observed depending on the enantiomeric purity (racemic mixture versus pure enantiomers) of an amidic receptor 7 used.


Mirror-image optic nerve dysplasia with associated anisometropia in identical twins.
Monozygotic (MZ) or "identical" twins arise from a single fertilized egg, which divides into two embryos at an early stage of development. As a result, MZ twins have identical genomes and are always of the same sex. A case of optic nerve hypoplasia and anisometropia, in association with mirror-image presentation in a set of 12-year-old identical twins, is reported. The monozygotic twinning event responsible for identical twins--as well as the rare phenomenon of mirror imaging--is described. The combined occurrence of anisometropia and optic nerve hypoplasia in mirror-image presentation in a set of monozygotic twins provides a unique opportunity to study the genetic versus environmental influences on the development of optic nerve hypoplasia. Although the cause of optic nerve hypoplasia remains unclear, its associated mirror-image presentation in this case suggests a possible genetic predisposition.


Risk of hand dermatitis among hairdressers versus office workers.
The risk of irritant skin damage associated with hairdressing was estimated with the individual occupational exposure and other relevant factors having been taken into consideration. A cohort of 2352 hairdressing and 111 office apprentices was prospectively followed for the duration of their vocational training (3 years), 3 examinations having been made and 3 years of recruitment having been used [1992 (hairdressers only), 1993, 1994] in 15 vocational training schools in northwest Germany. The information of the final follow-up examination was used for the analysis. A multifactorial analysis taking several (constitutional) risk factors, which were unevenly distributed between the 2 groups, into account revealed a significantly increased risk for hairdressers when compared with office workers (odds ratio approximately 4.0) with a marked decline in the most recently recruited (1994) apprentice group. Other significant factors increasing the dermatitis risk were (i) low ambient absolute humidity, (ii) young age, and (iii) a certain higher range of "atopy score". If the individual profile of occupational exposure among hairdressers was also considered, unprotected wet work of more than 2 hours per day was found to be a significant risk factor. Good skin protection, as operationalized in the present study, can diminish, but not eliminate, the risk of occupational irritant hand dermatitis among hairdressers.


Reflex sympathetic dystrophy after modified radical mastectomy: a case report.
Despite the long history of descriptions of reflex sympathetic dystrophy (RSD), much confusion remains regarding its pathogenesis, diagnosis, and treatment. It most commonly occurs after trauma and is more frequent in women, white persons, and the elderly. The first case of RSD after mastectomy is reported and the proposed pathophysiology and management of RSD are reviewed.