[Chronic infections and osteochondrosis of the spine].
Out of 144 patients suffering from cervical osteochondrosis, single or multiple foci of chronic infection (ENT infection, bronchitis, pneumonia, cholecystitis, pyelonephritis, ect.) were found in 99. All of them had various combinations of symptoms indicating lesions of the radices spinales, cervical spine, insufficient circulation in the vertebrobasilar area. Literature and first-hand experience suggest a conclusion on the underlying infection and allergic processes in development of the disk ossification. Relevant treatment modalities are recommended.


Hybrid intelligent systems for time series prediction using neural networks, fuzzy logic, and fractal theory.
In this paper, we describe a new method for the estimation of the fractal dimension of a geometrical object using fuzzy logic techniques. The fractal dimension is a mathematical concept, which measures the geometrical complexity of an object. The algorithms for estimating the fractal dimension calculate a numerical value using as data a time series for the specific problem. This numerical (crisp) value gives an idea of the complexity of the geometrical object (or time series). However, there is an underlying uncertainty in the estimation of the fractal dimension because we use only a sample of points of the object, and also because the numerical algorithms for the fractal dimension are not completely accurate. For this reason, we have proposed a new definition of the fractal dimension that incorporates the concept of a fuzzy set. This new definition can be considered a weaker definition (but more realistic) of the fractal dimension, and we have named this the "fuzzy fractal dimension." We can apply this new definition of the fractal dimension in conjunction with soft computing techniques for the problem of time series prediction. We have developed hybrid intelligent systems combining neural networks, fuzzy logic, and the fractal dimension, for the problem of time series prediction, and we have achieved very good results.


Optimization of Electronically Monitored Non-Adherence in Highly Adherent Renal Transplant Recipients by Reducing the Dosing Frequency - A Prospective Single-Center Observational Study.
Non-adherence (NA) after renal transplantation poses a major risk for allograft rejection, graft loss, and patient mortality. Yet, there is still ambiguity about its etiology and its possible relationships with patient-related factors. In order to prevent poor outcomes after transplantation, it is crucial to gain a more refined understanding of potential determinants, to identify patients at risk, and to intervene accordingly. The objective of this study was to assess potential risk factors of NA by prospectively applying electronic monitoring. This was a single-center prospective observational study. Prior to study initiation, sociodemographic, biomedical, and psychosocial variables (depression, health-related quality of life, self-efficacy, social support, attachment, experiences and attitudes towards immunosuppressive medication, emotional responses after organ transplantation, satisfaction with information about immunosuppressive medication, and perceptions and beliefs about medications) were assessed. Thereafter, immunosuppressive adherence behavior was measured prospectively via electronic monitoring (EM, VAICA©) during a 3-month period to receive the percentage frequency of Taking and Timing Adherence (±2h, ±30min) for each patient. Focus of this study was the phase of medication implementation. A total of 78 patients participated in our study (mean age 55.28, 56% male). We found rates of 99.39% for Taking Adherence, 98.34% for Timing Adherence ±2h, and 93.34% for Timing Adherence ±30min, respectively. Multiple regression analyses revealed that the type of medication could significantly predict Taking Adherence. Patients receiving Advagraf© (once daily) depicted better Taking Adherence than patients receiving Prograf© (twice daily) (p=0.04). No associations were found for Timing Adherence (±2h, ±30min). Sociodemographic, biomedical, or psychosocial variables were not found to be associated with adherence behavior. In highly adherent populations, only a few factors can be altered to improve adherence. Changing the immunosuppressive regimen from twice-daily to once-daily could be an option for optimizing adherence. However, risk factors for NA could be different in a less adherent population.


Brucellosis: serological methods compared.
At least 12 persons contracted clinical, and 4 persons subclinical Brucella melitensis infection during a brucellosis epidemic in the spring and summer of 1983 in Southern Germany, a region which had been free of this disease for the past 20 years. All cases of illness were traced to one infected herd of sheep. The presence of antibodies against B. melitensis was examined in 72 sera of infected patients using the following tests: agglutination, Coomb's test, two complement fixation tests with different antigen preparations (CFT 1 and 2), IgG and IgM enzyme-linked immunosorbent assay (ELISA), and opsonophagocytosis; and the occurrence of cross-reacting antibodies against Yersinia enterocolitica O 9 was investigated in the agglutination and complement fixation tests. Sera from 100 blood donors and 112 other people with close contact with sheep were also examined. The results revealed the need to consider an intermediate range in the interpretation of ELISA results--due to elevated values of persons in groups at risk but without clinical signs of illness. In all other tests, however, such persons revealed the same cut-off levels as the general population. Results from all initial sera of infected persons revealed titres of optical densities above the baseline levels determined in the present study, with the exception of the Coomb's and CFT2 tests. The agglutination test, but not brucella CFT2, revealed complete cross-reactivity between Y. enterocolitica O 9 and B. melitensis. ELISA stood out as the only test which is suited to diagnosis of both recent and past infection, since ELISA IgM determination permits conclusions about the time of the onset of illness, and determination of IgG may still yield values above the cut-off level up to 623 days after the onset of illness. In 2 of the 16 infected persons, IgG ELISA was the only test revealing previous infection 424 and 528 days after the onset of illness. A procedural scheme is presented which may help to simplify the diagnosis of brucellosis.


Postsynaptic Ca2+ influx mediated by three different pathways during synaptic transmission at a calyx-type synapse.
Whole-cell recordings and Ca2+ flux measurements were made at a giant calyx-type synapse in rat brainstem slices to determine the contribution of glutamate receptor (GluR) channels and voltage-dependent Ca2+ channels (VDCCs) to postsynaptic Ca2+ influx during synaptic transmission. A single presynaptic action potential (AP) evoked an EPSP, followed by a single AP. The EPSP-AP sequence caused a postsynaptic Ca2+ influx of approximately 3.0 pC, primarily through VDCCs ( approximately 70%) and NMDA-type (up to 30%) channels but also through AMPA-type (<5%) GluR channels. At -80 mV, the fractional Ca2+ current (Pf) mediated by AMPA receptor (AMPAR) and NMDA receptor (NMDAR) channels was 1.3 and 11-12%, respectively. Simulations of the time course of Ca2+ influx through GluR channels suggested that the small contribution of AMPAR channels occurred only during the first few milliseconds of an EPSP, whereas influx through NMDAR channels dominated later. The NMDAR-mediated Ca2+ influx was localized in regions covered by the presynaptic terminal, whereas the Ca2+ influx mediated by VDCCs was more homogeneously distributed. Because of the temporal and spatial differences, calcium ions entering through the three different pathways are likely to activate different intracellular targets in the postsynaptic cell.


Osteitis fibrosa cystica mistaken for malignant disease.
A 65-year-old man with back pain had plain radiographs that showed multiple osteolytic bone lesions of the pelvis, femur and L-spine; an magnetic resonance imaging scan of the L-spine showed extensive bony resorption with a posterior epidural mass involving the L1 spinous process; these findings suggested multiple myeloma or bony metastasis. However, all serology testing was negative. The parathyroid hormone and serum calcium levels were found to be abnormally elevated. A fine needle aspiration biopsy suggested that the L-spine lesion was consistent with the diagnosis of osteitis fibrosa cystica. A pathological fracture of the spine compressed the spinal cord, and surgical intervention was required. The neck computed tomography and Tc-99m sestamibi scan showed a solitary parathyroid mass. A minimally invasive parathyroidectomy using intraoperative parathyroid hormone monitoring was performed and two enlarged parathyroid glands identified. This case illustrates the importance of the consideration of a rare brown tumor associated with primary hyperparathyroidism in patients with the bone lesions suggestive of a malignancy.


Investigation of chicken intestinal bacterial communities by 16S rRNA targeted fluorescence in situ hybridization.
The aim of the investigation was to quantify selected dominant bacterial groups in the chicken intestinal tract. Conventional production was used as model and the effect of the supplement with Salinomycin was evaluated. Hybridization conditions were optimized for published probes with respect to a panel of reference bacteria. In chicken intestinal samples bacteria were quantified by fluorescence in situ hybridization with 16S rRNA oligonucleotides directed towards bacteria related to Lactobacillus, Bacillus, Enterococcus-Streptococcus-Lactococcus, Enterobacteriaceae, Bacteroides, Clostridium and the domain Bacteria in lumen of ileum and cecum as well as on the intestinal wall including mucus of four individuals. Salinomycin in feed reduced counts of the Lactobacillus-, Enterobacteriaceae- and Clostridium-like bacteria in lumen of ileum compared to the conventional control. Increased or decreased bacterial counts were registered by Salinomycin in the ceca compared to the control. Relatively higher counts of Bacteroides- and Clostridium-like bacteria were found on the intestinal wall including mucus compared to lumen. The increase in numbers of some bacterial groups as well as the expected reduction by Salinomycin and the observed difference in the relative distribution of bacteria between lumen and intestinal wall are new observations that will need further investigation.


[Electrolyte imbalance in suckling with broncho - pneumonia].
The authors describe responsable mechanisms leading to electrolyte imbalance of the suckling with broncho - pneumonia. They outline the physiopathological and etiological nursing problems and present, as far as they believe, an adequate nursing treatment, focalyzing specific areas, such as: vital signs, skin and mucosa, nutrition and hidra-tion, voiding, sleep and rest, including sensory and phycho-social conditions.


Implementation and validation of swept density reflectometry for integrated data analysis at ASDEX Upgrade.
In the tokamak ASDEX Upgrade, Integrated Data Analysis (IDA) is used to infer plasma quantities, such as electron density, using heterogeneous data sources. Essential is forward modeling from the parameter space into the data space with physically reasonable models for probabilistic evaluation. This paper presents a new forward model for O-mode profile reflectometry, a necessary prerequisite for Bayesian inference and inclusion in IDA. An efficient forward model based on the analytic solution for a piece-wise linear density description allows IDA to overcome problems associated with the established determination of cut-off locations via Abel inversion and Bottollier-Curtet's method. Instead of using a hard-coded initialization for densities below the first measured cut-off density, other diagnostics, such as the lithium beam, are used to analyze the shape of the initial part of the profile. Error propagation from the measured data, and other uncertain sources, to the uncertainties in the density profile and also its gradient is an intrinsic property of the probabilistic approach, which benefits from the joint analysis. Missing or ambiguous data do not prevent the profile evaluation, but only increase the uncertainty for densities in the affected range. Density profiles together with their uncertainties are determined by the joint analysis of complementary diagnostics, with the newly added reflectometry closing a gap in the outer core region. A stand-alone inversion based on the new forward model, including uncertainty quantification, is introduced, optionally providing an n(R) profile with uncertainties and a gradient. This method is a candidate for real-time analysis, providing error bars.


Cranial Melioidosis Presenting as Osteomyelitis and/or Extra-Axial Abscess: Literature Review.
Central nervous system (CNS) melioidosis is rare. Clinical presentations depend on the region of endemicity. Despite treatment, neurologic disease has relatively high mortality rates. Less than 80 cases of CNS involvement have been reported. A literature review was performed by searching online databases for melioidosis presenting as osteomyelitis or scalp/extra-axial abscess (OSEAA). In addition, 3 similar cases managed at my institute have been presented. Including this report of 3 cases, 20 additional cases have been reported. Of these, 12 cases (60%) were from India. The mean age of patients was 45.5 years (range, 29-74 years), and none were in the pediatric age group. Patients in the fifth to sixth decades were most frequently affected. The male to female ratio was 5.3:1. Eleven patients had predisposing factors. Fever, headache, and scalp swelling were the most common features. Five cases had history of previous melioid infection. Seven cases had systemic disease. Debridement was performed in 11 cases. The average intensive phase treatment duration was 4.6 weeks (range, 2-8 weeks) and 5.5 months (range, 3-12 months) for the maintenance phase. Mean follow-up duration was 13.5 months (range, 2 weeks-40 months). Two deaths (10%) were reported, and 1 case of residual frontal abscess had relapse. Cranial melioidosis presenting as OSEAA is associated with good outcome, in contrast with other neurologic presentations. Intensive phase for at least 2-3 weeks followed by maintenance phase for 3-6 months is the standard treatment, similar to other melioid presentations. A high degree of suspicion and accurate identification of the organism is crucial. Patients need to be monitored for recurrences, both clinically and radiologically.


Von Recklinghausen neurofibromatosis and acute leukemia.
The leukemias are neoplastic processes that have been associated with a variety of genetic disorders. A case of an adolescent with both acute myelomonocytic leukemia and von Recklinghausen disease is presented, and the literature reviewed to show that these two diseases are associated. Although the number of cases in the literature suggests that in children with von Recklinghausen disease there is a greater risk of leukemia developing, prospective studies are needed to prove this point.


Development and Pretesting of a Questionnaire to Assess Patient Experiences and Satisfaction with Medications (PESaM Questionnaire).
The aim of this study was to develop, together with the Lung Foundation Netherlands and Dutch Kidney Patients Association, patients and clinicians, a measure to evaluate patient experiences with the orphan drugs pirfenidone (for idiopathic pulmonary fibrosis [IPF]) and eculizumab (for atypical haemolytic uraemic syndrome [aHUS]), as well as a generic measure of patient experiences and satisfaction with medications. Development of the Patient Experiences and Satisfaction with Medications (PESaM) questionnaire consisted of four phases: literature review (phase I); focus groups and individual patient interviews (phase II); item generation (phase III); and face and content validity testing (phase IV). Literature review aimed to identify existing disease-specific and generic patient experience measures to provide guidance on the domains of medication use relevant to patients, the number of items and type of response categories, and to generate an initial pool of items. Subsequent focus groups and patient interviews were conducted to gain insight into the perceived effectiveness of the therapies, the burden of side effects, and how the medication impacted on a patient's daily life. Focus groups and interviews were recorded and transcribed verbatim. Coding was carried out by highlighting passages in the text and assigning each passage a code representing the following predefined categories: (1) perceived effectiveness; (2) side effects; (3) ease of use; and (4) impact of medication. Using data from phase I and II, a panel of experts selected items relevant for inclusion in the questionnaire. Individual patient interviews with IPF and aHUS patients (n = 18), using a retrospective verbal probing technique, were conducted to assess face validity, time needed to fill out the questionnaire, and content validity. The PESaM questionnaire that was developed consisted of two disease-specific modules that assessed patient experiences with pirfenidone for the treatment of IPF, and eculizumab for the treatment of aHUS, a generic module, applicable to any medication, and a module to assess patient expectations. Review of the literature identified multiple disease- or medication-specific questionnaires and two generic patient satisfaction questionnaires. Common domains across most questionnaires were effectiveness, side effects, ease of use and overall satisfaction. Patient interviews revealed the social impact (e.g. unable to go outside) of side effects such as photosensitivity associated with pirfenidone and the risk of infection associated with eculizumab. Each PESaM module focuses on patients' perceived effectiveness of the medication, side effects, and ease of use, and the impact these aspects have on physical and emotional health and daily life. The generic module additionally includes items related to satisfaction with the medication. Individual interviews with patients in phase IV confirmed, in general, that questions and response options of the modules were clear and content validity was good. The mean time to complete the modules ranged from 6 min for the disease-specific (aHUS) module to 9 min for the generic module. We developed the PESaM questionnaire to quantitatively assess patient experiences and satisfaction with medications. A validation study is currently underway to examine the psychometric properties of the PESaM questionnaire.


Influence of clinical therapy and nutritional counseling on the recurrence of urolithiasis.
To evaluate the influence of combined clinical therapy and nutritional guidance on the recurrence of urolithiasis. From our registry of patients with recurrent urolithiasis we selected 57 who had at least 5-years of follow-up. We collected 24h urine samples in order to analyze Ca, Na, uric acid, citrate, oxalate, and Mg concentrations and to assess urine volume. Patients filled out a clinical questionnaire before treatment, and abdominal radiographs and/or ultrasound were performed both before treatment and during the follow-up period. During follow-up, specific and individualized dietary advice was given based on the individual's metabolic disorders. Patients also received specific pharmacological treatment for their metabolic alterations. Outcome measures were metabolites in urine and the urolith recurrence rate. Pre- and post- intervention values were compared using tests as appropriate. Fifty six of the patients were male and the majority of patients were overweight. The mean BMI was 27 kg/m(2). Urinary excretion of calcium, uric acid and sodium decreased significantly over the five year follow-up period. The number of uroliths that formed during the 5-year follow-up also decreased significantly compared to pre-treatment values. Individualized dietary advice combined with pharmacological treatment significantly reduces long-term urolithiasis recurrence.


Characteristics of the ideal sex partner: gender differences and perceptions of the preferences of the other gender.
The objective of the current study was to further examine gender differences in preferences for particular characteristics in a sexual partner and to investigate the extent to which men and women accurately estimate the preferences of the other gender. Heterosexual college students (185 men, 244 women) rated a diverse set of characteristics in a hypothetical sexual partner with whom they were presumed to be involved in an ongoing relationship. Participants also responded to the same set of items with regard to estimates of the ratings of the other gender (order of presentation was counter-balanced). Although there was notable similarity in what men and women most valued in a potential long-term sex partner, there were gender differences with regard to ratings of several of the items. Also, men and women under- or overestimated the ratings of the other gender with regard to several characteristics. Results are discussed with regard to implications for intervention as well as directions for future research.


The course of hepatitis E virus infection in pigs after contact-infection and intravenous inoculation.
Worldwide, hepatitis E virus (HEV) genotype 3 is observed in pigs and transmission to humans is implied. To be able to estimate public health risks from e.g. contact with pigs or consumption of pork products, the transmission routes and dynamics of infection should be identified. Hence, the course of HEV-infection in naturally infected pigs should be studied. To resemble natural transmission, 24 HEV-susceptible pigs were infected either by one-to-one exposure to intravenously inoculated pigs (C1-pigs; n = 10), by one-to-one exposure to contact-infected pigs (C2-pigs: n = 7; C3-pigs: n = 5) or due to an unknown non-intravenous infection route (one C2-pig and one C3-pig). The course of HEV-infection for contact-infected pigs was characterized by: faecal HEV RNA excretion that started at day 7 (95% confidence interval: 5-10) postexposure and lasted 23 (19-28) days; viremia that started after 13 (8-17) days of faecal HEV RNA excretion and lasted 11 (8-13) days; antibody development that was detected after 13 (10-16) days of faecal HEV RNA excretion. The time until onset of faecal HEV RNA excretion and onset of viremia was significantly shorter for iv-pigs compared to contact-infected pigs, whereas the duration of faecal HEV RNA excretion was significantly longer. At 28 days postinfection HEV RNA was detected less frequently in organs of contact-infected pigs compared to iv-pigs. For contact-infected pigs, HEV RNA was detected in 20 of 39 muscle samples that were proxies for pork at retail and in 4 of 7 urine samples. The course of infection differed between infection routes, suggesting that contact-infection could be a better model for natural transmission than iv inoculation. Urine and meat were identified as possible HEV-sources for pig-to-pig and pig-to-human HEV transmission.


Interleukin-11 induces Th2 polarization of human CD4(+) T cells.
Exploration of the immunomodulatory activities of the multifunctional cytokine interleukin-11 (IL-11) has prompted several therapeutic applications. The immunomodulatory effects of IL-11 on human antigen-presenting cells and on T cells were investigated. IL-11 inhibited IL-12 production by activated CD14(+) monocytes, but not by mature dendritic cells (DCs) stimulated via CD40 ligation. Moreover, IL-11 did not affect either DC maturation, as demonstrated by phenotypic analysis and evaluation of cytokine production, or DC generation from progenitor cells in the presence of specific growth factors. Molecular analysis demonstrated the expression of IL-11 receptor messenger RNA in highly purified CD14(+) monocytes, CD19(+) B cells, CD8(+), and CD4(+) T cells, and CD4(+)CD45RA(+) naive T lymphocytes. In keeping with this finding, IL-11 directly prevented Th1 polarization of highly purified CD4(+)CD45RA(+) naive T cells stimulated with anti-CD3/CD28 antibodies, as demonstrated by significant increases of IL-4 and IL-5, by significantly decreased interferon-gamma production and by flow cytometry intracellular staining of cytokines. Coincubation of naive T cells with DCs, the most potent stimulators of Th1 differentiation, did not revert IL-11-mediated Th2 polarization. Furthermore, parallel experiments demonstrated that the activity of IL-11 was comparable with that induced by IL-4, the most effective Th2-polarizing cytokine. Taken together, these findings show that IL-11 inhibits Th1 polarization by exerting a direct effect on human T lymphocytes and by reducing IL-12 production by macrophages. Conversely, IL-11 does not exert any activity on DCs. This suggests that IL-11 could have therapeutic potential for diseases where Th1 responses play a dominant pathogenic role.


Probiotics prevent death caused by Citrobacter rodentium infection in neonatal mice.
Intestinal bacterial infections are a major cause of morbidity and mortality, especially in neonates. Therefore, the aims of this study were to characterize Citrobacter rodentium infection in neonatal mice and determine the role played by specific probiotics in ameliorating disease severity. Infection of C57BL/6 mice with C. rodentium was performed at postnatal day 14. A subset of mice was pretreated orally with either a mixture of Lactobacillus rhamnosus and Lactobacillus helveticus or placebo, starting at 7 days. To study the effects of B and T cells, rag1(-/-) and JH(-/-) mice were used, with survival, colonic crypt depth, and barrier function evaluated as outcome measures. C. rodentium infection caused weight loss and death. In contrast, survival was maintained by daily treatment with Lactobacilli. Weight loss, colonic epithelial cell hyperplasia, mucosal barrier dysfunction, and elevated serum corticosterone levels in C. rodentium-infected wild-type mice were ameliorated by probiotics, but not in rag1(-/-) animals. Beneficial effects of probiotics were observed in B cell-deficient (JH(-/-)) mice, indicating the requirement of T cells in reducing the adverse sequelae of neonatal enteric infection. These findings demonstrate that C. rodentium infection in newborn mice causes death and that probiotics promote survival, but only in the presence of T cells.


[Nontuberculous mycobacterial lymphadenitis].
A 4-year-old girl was referred with a chronically enlarged left cervical lymphadenitis of the neck. This swelling appeared to be caused by a Mycobacterium avium infection. Mycobacterium avium belongs to the group of nontuberculous mycobacteria. These micro-organisms can cause a cervicofacial lymphadenitis in children in the head and neck region. The children are healthy, and are seen to have a submandibular or preauricular swelling. Early recognition of the disease is important because it gives the best chance that treatment will result in a successful outcome.


Functional and cosmetic results of a lower eyelid crease approach for external dacryocystorhinostomy.
External dacryocystorhinostomy is routinely performed through a cutaneous vertical incision placed on the lateral aspect of the nose. The lower eyelid crease approach has been seldom reported. The purpose of this study is to report the cosmetic and functional results of the lid crease approach for external dacryocystorhinostomy in a series of patients. Prospective, interventional case series. Twenty-five consecutive patients (17 women) ranging in age from 3 to 85 years (mean ± SD= 44.84 ± 23.67) were included in the study. All patients but one underwent unilateral external dacryocystorhinostomy with a 10 to 15 mm horizontal incision placed on a subciliary relaxed eyelid tension line. The inner canthus was photographed with a Nikon D70S digital camera with a macrolens and resolution of 3008 x 2000 pixels at 1, 3 and 6 months after surgery. The resulting scar was judged from the photographs by 3 observers (ophthalmologist, plastic and head and neck surgeons) according to a four level scale (1= unapparent, 2= minimally visible, 3= moderately visible, 4= very visible). The surgery was easily performed in all patients with a 90.48% success. Three of the elderly patients (ages 61, 79 and 85 yr) developed mild lacrimal punctum ectropion, which resolved with conservative treatment. One patient had a hypometric blink which spontaneously recovered within one month. The mean score for scar visibility was 2.19 (1(st) mo), 1.65 (3(th) mo) and 1.44 (6(th) mo). The eyelid crease approach is an excellent option for external dacryocystorhinostomy. It leaves an unapparent scar since the first month after surgery, even in younger patients. The functional results are excellent and comparable to other techniques. Care should be taken in elderly patients with lower eyelid laxity in order to prevent lacrimal punctum ectropion.


The transglutaminase type 2 and pyruvate kinase isoenzyme M2 interplay in autophagy regulation.
Autophagy is a self-degradative physiological process by which the cell removes worn-out or damaged components. Constant at basal level it may become highly active in response to cellular stress. The type 2 transglutaminase (TG2), which accumulates under stressful cell conditions, plays an important role in the regulation of autophagy and cells lacking this enzyme display impaired autophagy/mitophagy and a consequent shift their metabolism to glycolysis. To further define the molecular partners of TG2 involved in these cellular processes, we analysed the TG2 interactome under normal and starved conditions discovering that TG2 interacts with various proteins belonging to different functional categories. Herein we show that TG2 interacts with pyruvate kinase M2 (PKM2), a rate limiting enzyme of glycolysis which is responsible for maintaining a glycolytic phenotype in malignant cells and displays non metabolic functions, including transcriptional co-activation and protein kinase activity. Interestingly, the ablation of PKM2 led to the decrease of intracellular TG2's transamidating activity paralleled by an increase of its tyrosine phosphorylation. Along with this, a significant decrease of ULK1 and Beclin1 was also recorded, thus suggesting a block in the upstream regulation of autophagosome formation. These data suggest that the PKM2/TG2 interplay plays an important role in the regulation of autophagy in particular under cellular stressful conditions such as those displayed by cancer cells.


Iron supplementation of total parenteral nutrition: a prospective study.
A prospective study to evaluate the iron dosage needed to restore serum iron levels was performed on patients receiving prolonged total parenteral nutrition (TPN). Intravenous iron intakes of 0, 25, 87.5, and 175 mg/wk were sequentially studied. No untoward responses were seen in 42 patients studied for 2758 patient days. When compared to pre-TPN levels, serum iron levels increased significantly with increasing iron dosage (p less than 0.002). In every single patient at the two highest dosage levels, serum iron levels at 3 wk rose from the pre-TPN level. Hemoglobin, reticulocyte count, transfusion requirement, total iron binding capacity, and red cell indices were not affected by iron dosage. There was no increased incidence of sepsis in patients who received increasing iron dosage. Both the 87.5 and 175 mg/wk iron doses increased serum iron levels from pre-TPN values, but the highest dose increased serum iron levels above the normal range in 80% of patients after 3 wk of administration allowing us to recommend the 87.5 mg/wk dose.


Acquiring Hyperpolarized 129Xe Magnetic Resonance Images of Lung Ventilation.
Hyperpolarized 129Xe MRI comprises a unique array of structural and functional lung imaging techniques. Technique standardization across sites is increasingly important given the recent FDA approval of 129Xe as an MR contrast agent and as interest in 129Xe MRI increases among research and clinical institutions. Members of the 129Xe MRI Clinical Trials Consortium (Xe MRI CTC) have agreed upon best practices for each of the key aspects of the 129Xe MRI workflow, and these recommendations are summarized in a recent publication. This work provides practical information to develop an end-to-end workflow for collecting 129Xe MR images of lung ventilation according to the Xe MRI CTC recommendations. Preparation and administration of 129Xe for MR studies will be discussed and demonstrated, with specific topics including choice of appropriate gas volumes for entire studies and for individual MR scans, preparation and delivery of individual 129Xe doses, and best practices for monitoring subject safety and 129Xe tolerability during studies. Key MR technical considerations will also be covered, including pulse sequence types and optimized parameters, calibration of 129Xe flip angle and center frequency, and 129Xe MRI ventilation image analysis.


Implementation of 3D Printing and Computer-Aided Design and Manufacturing (CAD/CAM) in Craniofacial Reconstruction.
The need for precision in craniomaxillofacial surgery has necessitated the evolution of new technology to improve patient outcomes and subsequently augment the road to recovery. Surgical planning has variables that may influence outcomes, including the image quality, image acquisition and image processing. Our review focuses on the advancement of three dimensional (3D) printing to create patient-specific constructs and therefore aims to study the current trends in the implementation of 3-D printing in craniofacial surgeries, including preferred 3-D printing techniques and materials, computer-aided design and manufacturing techniques, and outcomes as measured by recent studies. The authors conducted a systematic review following PRISMA guidelines to query PubMed, Embase, Cochrane library and ProQuest electronic databases. Mesh combinations and synonyms of "3Dprinting", "3Dprinted", "Craniofacial" were used. The authors included all original human studies that focused on the surgical implementation of 3D-printed implants for craniofacial defects. After screening 1253 studies, the authors included 49 articles consisting of a total of 745 subjects for qualitative analysis. Titanium (n = 13) and polycaprolactone (n = 6) were the most common 3D printed materials studied while Color Jet Printing (n = 12) and Stereolithography (n = 11) were the most common techniques. All studies that compared implants acquired by 3D printing with those acquired by conventional approaches showed a significantly better prognosis, and reductions in operative time, length of stay, and immediate complications. The use of patient-specific alternative materials, planning software and 3-D printing techniques shows satisfactory results in craniofacial reconstruction. Future studies should include standard levels of objective measurements to make better comparisons.


[Effects of dopamine administered at the time of cadaver donor conditioning on the course of acute postischemic insufficiency of the renal allotransplant].
The various doses of dopamine efficacy, applied for the inotropic support in 30 donors of kidneys, was investigated, as well as the preparation influence on the renal transplantation function. Inotropic support of donor using dopamine was needed in 21 donors. The occurrence rate of an acute necrosis of tubules have depended upon dopamine doses. Dopamine is the preparation of choice for the intensive therapy conduction and securing of cardiovascular stability of the donors kidneys.


Implementation of complex adaptive chronic care: the Patient Journey Record system (PaJR).
The Patient Journey Record system (PaJR) is an application of a complex adaptive chronic care model in which early detection of adverse changes in patient biopsychosocial trajectories prompts tailored care, constitute the cornerstone of the model. To evaluate the PaJR system's impact on care and the experiences of older people with chronic illness, who were at risk of repeat admissions over 12 months. Community-based cohort study - random assignment into intervention and usual care group, with process and outcome evaluation. Adult and older patients with multiple morbidity, one or more chronic diseases with one or more overnight hospitalizations, and seven or more general practice visits in the past 6 months. COMPLEX INTERVENTION: PaJR lay care guides/advocates call patients and their caregivers. The care guides summarize their semi-structured conversations about health concerns and well-being. Predictive modelling and rules-based algorithms trigger alerts in relation to online call summaries. Alerts are acted upon according to agreed guidelines. Descriptive and comparative statistics. Impact on unplanned emergency ambulatory care sensitive admissions (ACSC) with an overnight stay; sensitivity of alerts and predictions; rates of care guides-supported activities. Five part-time lay care guides and a care manager monitored 153 intervention patients for 500 person months with 5050 phone calls. The 153 patients in the intervention group were comparable to the 61 controls. The intervention group reported in 50% of calls that their health limited their social activities; and one-third of calls reported immediate health concerns. Predictive analytics were highly sensitive to risk of hospitalization. ACSC admissions were reduced by 50% compared to controls across the sites. The initial implementation of a complex patient-centred adaptive chronic care model using lay care guides, supported by machine learning, appeared sensitive to risk of hospitalization and capable of stabilizing illness journeys in older patients with multi-morbidity. Actions based on alerts produced in this study appeared to significantly reduce hospitalizations. This paves the way for further testing of the model.


Stress-induced hyperlocomotion as a confounding factor in anxiety and depression models in mice.
Chronic stress is broadly used to model anxiety and depression. However, in chronic stress models, anxiety- and depression-like behaviors might be masked by unspecific effects of stress. We tested whether chronic stress in mice can induce unspecific changes in locomotion, and whether these changes interfere with the measurement of anxiety and forced-swimming behaviors. Also, we studied these latter behaviors in relation to the duration of stress, the lighting conditions during testing, and after the injection of diazepam. We employed a 4-week chronic stress paradigm, adopted from a model of stress-induced anhedonia and a 1-week subchronic stress, both consisting of rat exposure, restraint stress and tail suspension. Chronically stressed mice, tested under bright and moderate illumination, exhibited 'anxiolytic-like' behavior along with prolonged swimming and hyperactivity. These behaviors were not detectable under weak illumination or after the injection of diazepam (0.25 mg/kg). Instead, normal locomotion, increased anxiety and inhibited swimming were revealed under these conditions. Thus, chronic stress can induce hyperlocomotion in mice, which is triggered by acute stressors such as light, and interferes with the evaluation of anxiety and forced swimming. One week of stress did not change locomotion and forced swimming, and increased anxiety irrespective of illumination applied during testing. Our data can possibly explain previously reported contradictions in the behavioral testing of mice with chronic stress models of anxiety and depression.


Self-Assembling 2D Arrays with de Novo Protein Building Blocks.
Modular self-assembly of biomolecules in two dimensions (2D) is straightforward with DNA but has been difficult to realize with proteins, due to the lack of modular specificity similar to Watson-Crick base pairing. Here we describe a general approach to design 2D arrays using de novo designed pseudosymmetric protein building blocks. A homodimeric helical bundle was reconnected into a monomeric building block, and the surface was redesigned in Rosetta to enable self-assembly into a 2D array in the C12 layer symmetry group. Two out of ten designed arrays assembled to micrometer scale under negative stain electron microscopy, and displayed the designed lattice geometry with assembly size up to 100 nm under atomic force microscopy. The design of 2D arrays with pseudosymmetric building blocks is an important step toward the design of programmable protein self-assembly via pseudosymmetric patterning of orthogonal binding interfaces.


Clinical cues for detecting ictal asystole.
The occurrence of asystole during an epileptic seizure is the most dramatic manifestation of ictal bradycardia. Recognition of ictal asystole is important as treatment with both antiepileptic drugs and cardiac pacing may be necessary. The purpose of this study was to identify clinical cues to aid in the detection of ictal asystole. We analyzed the clinical and electrophysiologic features of all recorded seizures in consecutive patients diagnosed with ictal bradycardia and asystole on prolonged video-EEG/ECG monitoring over a 14 year period. Twenty-nine seizures with ictal bradycardia were identified in 13 patients. Of these, 11 seizures in seven patients were associated with asystole. Bilateral transient limb movements consisting of asymmetric posturing or jerking occurred during eight episodes of ictal asystole, and loss of muscle tone occurred during four. In contrast, neither bilateral limb movement nor loss of muscle tone was observed in any of the non-asystolic seizures, whether ictal bradycardia was present or not. All patients with ictal asystole reported a history of seizure-related falls and brief body and limb jerking. The presence of loss of muscle tone or bilateral asymmetric jerky limb movements during a seizure suggests the possibility of ictal asystole. Video-EEG/ECG monitoring should be considered in patients with epilepsy demonstrating these clinical features to determine if ictal asystole is present.


Langerhans cell histiocytosis in Turkish children.
Langerhans cell histiocytosis (LCH) is a rare disorder with diverse forms of clinical presentation ranging from a benign course to diffuse progressive disease, and descriptions of LCH generally have been limited to single case reports and small case series. Since the condition is uncommon, we aimed in this study to describe our own experience and discuss the findings, treatment and outcome in our patients with LCH in light of the current literature. The eight patients (5 boys, 3 girls) ranged in age from 2 months to 3 years (mean 18 +/- 10.8 months). Multiple organ involvement was noted in 3, isolated bone involvement in 3, orbital involvement in 1, and pituitary gland involvement with rash in 1 patient. Treatment modalities used varied from simple observation to chemotherapy. Outcome results of our study demonstrated resolution of lesions in 5 patients and death in 2 patients. One patient with pituitary gland involvement developed diabetes insipidus and is receiving intranasal desmopressin acetate. Based on our results and a review of the literature, we recommend that any child with suspected solitary LCH undergo a full diagnostic investigation to rule out multiple lesions. A biopsy is recommended for a diagnosis at the time of presentation and should be attempted in any suspicious lesion. Chemotherapy is reserved for multiple systemic lesions and central nervous system (CNS) risk lesions. Follow-up investigations should be individualized but should consist of radiography and magnetic resonance imaging (MRI). Studies suggest that follow-up of at least four years is required.


Vaccine-associated contact paralytic poliomyelitis with atypical neurological presentation.
Paralytic poliomyelitis presenting with quadriparesis, transient encephalitis and bulbar symptoms in 2 patients in close contact with recently vaccinated children with trivalent live oral polio vaccine is described. Symmetrical lower motor neuron involvement of deltoid muscles with electromyographic confirmation was found. Upper motor neuron signs, with symmetrical hyperactive deep tendon reflexes developed in the lower extremities. Poliovirus Type-2 vaccine-like strain was cultured from one patient and both patients showed significant antibody titers rises to poliovirus. Attention is drawn to the possible clinical differences between vaccine associated poliomelitis and the usual features found in wild strain poliomyelitis. It is suggested that in selected cases, non-immunized contacts be given inactivated polio-vaccine when the vaccinees are immunized with the live oral-vaccine.


[Continuous non-invasive measurement of blood pressure].
Automatic continuous non-invasive measurement of blood pressure using the Penaz' principle (Finapres) was compared with the blood pressure records using a sphygmomanometer during anaesthesia in 29 patients without significant arteriosclerosis. There were no significant differences between values recorded using the two methods. Furthermore, the changes recorded in systolic, diastolic and mean arterial pressures were not significantly different. Also, the pulse recorded with the Penaz' principle corresponded to the heart rate recorded from ECG. Automatic continuous non-invasive measurement of blood pressure using the Penaz' principle offers a valuable aid for monitoring patients during anaesthesia.


Additively manufactured high-performance polymeric materials and their potential use in the oil and gas industry.
The oil and gas industry has been tagged as among the largest revenue-generating sectors in the world. High-performance polymers (HPPs), on the other hand, are among the most useful industrial materials, while the utility of 3D printing technologies has evolved and transitioned from rapid prototyping of composite materials to manufacturing of functional parts. In this prospective, we highlight the potential uses and industrial applications of 3D-printed HPP materials in the oil and gas sector, including the challenges and opportunities present.


The thioamides methimazole and thiourea inhibit growth of M. avium Subspecies paratuberculosis in culture.
Thyrotoxicosis is conceptualized as an "autoimmune" disease with no accepted infectious etiology. There are increasingly compelling data that another "autoimmune" affliction, Crohn disease, may be caused by Mycobacterium avium subspecies paratuberculosis (MAP). Like M. tb, MAP is systemic. We hypothesized that some cases of thyrotoxicosis may be initiated by a MAP infection. Because other thioamides treat tuberculosis, leprosy and M. avium complex, we hypothesized that a mode of action of some thioamide anti-thyrotoxicosis medications may include MAP growth inhibition. The effect of the thioamides, thiourea, methimazole and 6-propo-2-thiouracil (6-PTU) were studied in radiometric Bactec culture, on ten strains of three mycobacterial species (six of MAP, two of M. avium and two of M. tb. complex). Data are presented as "cumulative growth index," (cGI) or "percent decrease in cumulative GI" (%-DeltacGI). Methimazole was the most effective thioamide at inhibiting MAP growth. At 128microg/ml: MAP UCF-4; 65%-DeltacGI & MAP ATCC 19698; 90%-DeltacGI. Thiourea inhibited MAP "Ben" maximally; 70%-DeltacGI. Neither methimazole nor thiourea inhibited M. avium or M. tb. at the doses tested. 6-PTU has no inhibition on any strain studied, although a structurally analogous control, 5-PTU, was the most inhibitory thioamide tested. We show inhibition of MAP growth by the thioamides, thiourea and methimazole in culture. These data are compatible with the hypothesis that these thioamides may have anti-prokaryotic in addition to their well-established eukaryotic actions in thyrotoxic individuals.


Computerized analysis of the distribution of occlusal contacts in individuals with Parkinson's disease and temporomandibular disorder.
The aims of the present study were to determine the prevalence of temporomandibular disorder (TMD) in a sample of patients with Parkinson's disease (PD) and to analyze the distribution of occlusal contacts. The sample was composed of patients with PD aged 50-75 years. Temporomandibular disorder was evaluated using the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). The distribution of occlusal contacts was determined using the portable T-Scan III® occlusal analysis system during maximum voluntary clenching. Fisher's exact test was used to test the association between TMD and occlusal contact symmetry. Forty-two individuals with PD were analyzed. The prevalence of TMD was 23.8%. No statistically significant association was found between TMD and occlusal contact symmetry. Moreover, no significant difference in the distribution of occlusal contacts was found between the groups with and without TMD. The present data suggest no association between TMD and occlusal contact asymmetry in individuals with PD. The results of this study identified a prevalence of 23.8% of TMD signs in subjects with PD and a high frequency of occlusal asymmetry in this sample.


[Approaches to the combined therapy of helminthiases with leukinferon and etiotropic preparations].
The results of therapy with anthelmintics in combination with leukinferon show either higher efficiency of anthelmintics (medamin) or their same efficiency (albendazole). The outcomes of combined treatment of infected animals with anthelmintics and leukinferon are different and associated with the time of leukinferon administration as to the tissue stages of parasitic development, with the host's sensitivity and susceptibility to helminth.


Immunohistochemical localization of multispecific renal organic anion transporter 1 in rat kidney.
Renal proximal convoluted tubules have an important role, i.e., to excrete organic anions, including numerous drugs and endogenous substances. Recently, multispecific organic anion transporter 1 (OAT1) was isolated from rat kidney. In this study, the cellular and subcellular localization of OAT1 in rat kidney was investigated. Kidneys from normal rats were perfused and fixed with periodate-lysine-paraformaldehyde solution and were then processed for immunohistochemical analysis using the labeled streptavidin-biotin method, preembedding horseradish peroxidase method, and immunogold method. Light microscopic examination revealed immunostaining for OAT1 in the middle portion of the proximal tubule (S2 segment), but not in the initial portion of the proximal convoluted tubule, next to the glomerulus. Nephron segments other than the S2 segment and the renal vasculature were not stained with antibody to OAT1. Electron-microscopic observation using a preembedding method revealed that OAT1 was exclusively expressed in the basolateral membrane of S2 segments of proximal tubules. The immunogold method showed no labeling for OAT1 in the cytoplasmic vesicles, suggesting that OAT1 may not move together with organic anions into the cells. These results are consistent with previous physiologic data showing that organic anions, including para-aminohippurate, are taken up by the basolateral Na+-independent organic anion/dicarboxylate exchanger and excreted at S2 segments. In conclusion, OAT1 was localized to the basolateral membrane of S2 segments of proximal tubules in rat kidneys.


Radioactive uranium in various Indian tobaccos and consumable products (snuff, chutta, bidi and cigarette).
Tobacco is chewed in the form of snuff and thus its radioactivity--if there is any--goes directly into the body. Besides normal smoking, tobacco is also smoked in reverse manner in the form of "chutta", an indigenously prepared cigar made from the home grown plants of Nicotinia tobacum in South East coastal towns and villages in India. The burnt residue and the radioactive element--if there is any--in the case of chutta smoking will also go directly in the body causing hazardous effects. Uranium traces were determined in commercially available samples of snuff, chutta, bidi and cigarette tobacco using radiation damage etch technique. The analysis showed that uranium levels varied from 7.4 to 19.1 ppm in snuff, 0.16 to 0.37 ppm in chutta, 0.13 to 0.23 in bidi and 0.037 to 0.12 ppm in cigarette tobacco.


The mechanism of alpha-proton isotope exchange in amino acids catalysed by tyrosine phenol-lyase. What is the role of quinonoid intermediates?
To shed light on the mechanism of isotopic exchange of alpha-protons in amino acids catalyzed by pyridoxal phosphate (PLP)-dependent enzymes, we studied the kinetics of quinonoid intermediate formation for the reactions of tyrosine phenol-lyase with L-phenylalanine, L-methionine, and their alpha-deuterated analogues in D2O, and we compared the results with the rates of the isotopic exchange under the same conditions. We have found that, in the L-phenylalanine reaction, the internal return of the alpha-proton is operative, and allowing for its effect, the exchange rate is accounted for satisfactorily. Surprisingly, for the reaction with L-methionine, the enzymatic isotope exchange went much faster than might be predicted from the kinetic data for quinonoid intermediate formation. This result allows us to suggest the existence of an alternative, possibly concerted, mechanism of alpha-proton exchange.


Effect of whole soy and purified daidzein on ambulatory blood pressure and endothelial function--a 6-month double-blind, randomized controlled trial among Chinese postmenopausal women with prehypertension.
Although observational studies suggest that soy foods or isoflavones are cardio-protective, clinical trials on whole soy or isoflavone daidzein (one major isoflavone and the precursor of equol) on blood pressure (BP) and endothelial function (EF) are few and have not been specifically conducted among equol producers, a population most likely to benefit from soy treatment. We performed a 6-month double-blind, randomized, placebo-controlled trial to examine the effect of whole soy (soy flour) or purified daidzein on BP and EF in prehypertensive or untreated hypertensive postmenopausal women verified to be equol producers. A total of 270 eligible women were recruited and randomized to either one of the three treatment groups, 40 g soy flour (whole soy group), 40 g low-fat milk powder+63 mg daidzein (daidzein group) or 40 g low-fat milk powder (active control group) daily, each given as a solid beverage powder for 6 months. The primary outcome measures were 24 h ambulatory BP (ABP) and EF assessed by flow-mediated dilation using brachial artery ultrasound. A total of 253 subjects completed the study according to protocol. Urinary isoflavones indicated good compliance with the interventions. Intention to treat and per-protocol analysis indicated that there was no significant difference in the 6-month changes or % changes in parameters of ABP and brachial flow-mediated dilation among the three treatment groups. A further subgroup analysis among hypertensive women (n=138) did not alter the conclusions. Whole soy and purified daidzein had no significant effect on BP and vascular function among equol-producing postmenopausal women with prehypertension or untreated hypertension.


L1 retrotransposon and retinoblastoma: molecular linkages between epigenetics and cancer.
Long interspersed nuclear elements (LINEs) are mobile sequences shown to play a fundamental role in eukaryotic genome evolution. Recently, increasing interest has been directed at unveiling molecular mechanisms by which LINE-1 (L1), a ubiquitous member of this family, regulates gene expression and mammalian cell development, differentiation, and cancer. This mini review summarizes recent studies conducted to examine stress-induced L1 reactivation, with special attention given to the role of E2F/Rb transcription factors in epigenetic silencing of L1 and its potential role as a global modifier of chromatin structure and function. The last section focuses on the impact of histone deacetylase inhibitors in the regulation of gene function, chromatin structure, and cancer treatment through alterations in epigenetic signaling.


Patterns and correlates of use of evidence-based interventions to control diabetes by local health departments across the USA.
The nearly 3000 local health departments (LHDs) nationwide are the front line of public health and are positioned to implement evidence-based interventions (EBIs) for diabetes control. Yet little is currently known about use of diabetes-related EBIs among LHDs. This study used a national online survey to determine the patterns and correlates of the Centers for Disease Control and Prevention Community Guide-recommended EBIs for diabetes control in LHDs. A cross-sectional study was conducted to survey a stratified random sample of LHDs regarding department characteristics, respondent characteristics, evidence-based decision making within the LHD, and delivery of EBIs (directly or in collaboration) within five categories (diabetes-related, nutrition, physical activity, obesity, and tobacco). Associations between delivering EBIs and respondent and LHD characteristics and evidence-based decision making were explored using logistic regression models. Among 240 LHDs there was considerable variation among the EBIs delivered. Diabetes prevalence in the state was positively associated with offering the Diabetes Prevention Program (OR=1.28 (95% CI 1.02 to 1.62)), diabetes self-management education (OR=1.32 (95% CI 1.04 to 1.67)), and identifying patients and determining treatment (OR=1.27 (95% CI 1.05 to 1.54)). Although all organizational supports for evidence-based decision making factors were related in a positive direction, the only significant association was between evaluation capacity and identifying patients with diabetes and determining effective treatment (OR=1.54 (95% CI 1.08 to 2.19)). Supporting evidence-based decision making and increasing the implementation of these EBIs by more LHDs can help control diabetes nationwide.


Combination ACE inhibitor and angiotensin II receptor antagonist therapy in diabetic nephropathy.
The benefit of angiotensin-converting enzyme (ACE) inhibitor (i) therapy in diabetic glomerulosclerosis is thought to be largely the result of attenuation of angiotensin II (AngII) effects on blood pressure, glomerular hemodynamics and hypertrophy, and tissue fibrosis. The present study was undertaken to determine whether the addition of AngII receptor antagonist therapy to ACEi therapy in diabetic nephropathy results in attenuation of AngII effects beyond that achieved by ACEi therapy alone. Seven patients were studied as inpatients on the General Clinical Research Center each for 3 consecutive weeks as follows: week 1, the patients' usual regimen which included daily oral moderate to high dose ACEi therapy; week 2, the patients' usual regimen plus oral losartan (an antagonist (a) of the angiotensin type 1 receptor, AT1) 50 mg (n = 3) or 100 mg (n = 4) daily; week 3, return to the patients' usual regimen. Diet, physical activity, and blood glucose were held as constant as possible during the three weeks of daily testing. We found that plasma renin levels increased significantly during combination therapy and then returned to baseline values with discontinuation of AT1a therapy: mean baseline renin values (week 1) 3.0 ng/ml/min +/- 1.1 SE, mean renin values during combination therapy (week 2) 7.0 ng/ml/min +/- 3.2 (p = 0.0078 by Wilcoxon rank sum test), mean renin values after discontinuation of AT1a therapy (week 3) 3.9 ng/ml/min +/- 2.0 (NS compared to baseline values). In addition, 2 patients developed transient hypotension when losartan therapy was initiated. During this short-term study, 24-hour proteinuria, serum creatinine, serum potassium, and plasma aldosterone were not changed significantly by combination therapy. We conclude that in patients with diabetic nephropathy addition of AT1a therapy to ACEi therapy attenuates AngII effects better than ACEi therapy alone. We suggest that combination therapy for the management of diabetic glomerulosclerosis merits further investigation.


Treatment of segmental vitiligo with normal-hair follicle autograft.
Segmental vitiligo is a small subset albeit persistent form of focal vitiligo with dermatomal distributionand resistant to medical therapy. In recent years, surgical therapy as hair follicle autograft transplantationhas been a hot topic in management of segmental vitiligo. In this study, we evaluated the efficacy of thismethod in segmental vitiligo lesions. The study recruited 10 patients who suffered from resistant segmental vitiligo to evaluate the effectof transplantation of pigmented hair follicles on re-pigmentation of the affected area. In this method, one or twopunched-biopsy skin sample with a diameter of 5mm were harvested from occipital area of the scalps. Graftswere trimmed and divided into the follicular segments with at least one follicle in the interior and then insertedin the depigmented areas. Follow-up plan studies were scheduled to evaluate presence of pigmentation in theperifollicular areas. After 2 weeks, re-pigmentation was detectable surrounding the grafted hair follicles in 60 % of thecases. After 6 months, all of the patients had detectable re-pigmented area of about 2-9 mm. giving the surprising result of the study, hair follicle autograft transplant is an effective treatmentoption in the persistent segmental vitiligo.


Declining incidence of episodes of asthma: a study of trends in new episodes presenting to general practitioners in the period 1989-98.
A study was undertaken to determine trends in the incidence of new episodes of asthma presented to general practitioners participating in the Weekly Returns Service of the Royal College of General Practitioners, comprising 92 practices with a registered population of approximately 680 000 persons well distributed throughout England and Wales. These practices monitor the morbidity presented at every consultation, distinguishing between new episodes of illness and ongoing consultations. Age specific weekly rates of new episodes of asthma (and of acute bronchitis) presenting to the general practitioners over the years 1989-98 were examined in four week blocks and analysed by multiple regression, separating secular from seasonal trends. Quadratic trends in episodes of asthma were evident in each of the age groups with peaks in 1993/4. Corresponding analyses for acute bronchitis disclosed similar trends generally peaking in the winter of 1993/4. Mean weekly incidence data (all ages combined) decreased in all quarters since 1993. Regional analysis (North/Central/South) showed similar decreases. There has been a gradual decrease in the incidence of asthma episodes and of acute bronchitis presenting to general practitioners since 1993. The trend of an increase before 1993 followed by a decrease cannot be explained by changes in the patterns of health care usage or diagnostic preference of doctors.


The Russian gonococcal antimicrobial susceptibility programme (RU-GASP)--national resistance prevalence in 2007 and 2008, and trends during 2005-2008.
Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major problem worldwide. In the former Soviet countries including Russia, the knowledge regarding AMR has been highly limited. However, in 2004 the Russian gonococcal antimicrobial susceptibility programme (RU-GASP) was initiated. The aims of this study were to examine and describe the prevalence of N. gonorrhoeae AMR in 2007 and 2008 in Russia, and reveal trends in the period from 2005 to 2008. Gonococcal isolates (660 in 2007 and 900 in 2008) from 36 surveillance sites were examined using agar dilution method. From 2005 to 2008, the proportion of isolates resistant to spectinomycin increased from 0% to 7.2%, and remained high for those resistant to ciprofloxacin (approximately 49%). The resistance to azithromycin was 2.3% and 0.4% in 2007 and 2008, respectively. All isolates between 2005 and 2008 were susceptible to ceftriaxone. In conclusion, the AMR of N. gonorrhoeae in Russia is high, as in most countries in the European Union, and ceftriaxone should be the first line for treatment. If there is no access to ceftriaxone or in the presence of severe beta-lactam antimicrobial allergy, spectinomycin should be used; however, the resistance to spectinomycin has increased. Regular, quality-assured national and international surveillance of AMR in N. gonorrhoeae is crucial globally for public health.


Unmet needs of siblings of pediatric stem cell transplant recipients.
In 2010, the Bioethics Committee of the American Academy of Pediatrics issued recommendations that pediatric hematopoietic stem cell donors should have an independent advocate. Formulating appropriate guidelines is hindered by the lack of prospective empirical evidence from families about the experience of siblings during typing and donation. Our aim was to provide these data. Families with a child scheduled to undergo hematopoietic stem cell transplant were recruited. All family members, including children aged 9 to 22 years, were eligible. Qualitative interviews were conducted within 3 time periods: pretransplant, 6 to 8, and 9 to 11 months posttransplant. Quantitative scales assessing decision satisfaction and regret were administered at time 2. Thirty-three families were interviewed. Of the 119 family members, 76% perceived there was no choice in the decision to HLA-type siblings; 77% perceived no choice in sibling donation; 86% had no concerns about typing other than needle sticks; and 64% had no concerns about donation. Common concerns raised were dislike of needle sticks (19%), stress before typing results (14%), and fear of donation (15%). Posttransplantation, 33% of donors wished they had been given more information; 56% of donors stated they benefited from donation. Only 1 donor expressed regret posttransplant. Most family members did not view sibling typing and donation as a choice, were positive about the experience, and did not express regrets. We recommend education for all siblings before typing, comprehensive education for the donor by a health care provider pretransplant, and systematic donor follow-up after transplantation.


Misconceptions about the three point bony relationship of the elbow.
The 3 bony point relationship of the elbow is an important surface evaluation done in all cases of elbow pathology; its importance is highlighted by the fact that significant emphasis is also laid on this during the specialty board examinations. Confusion about the exact inter relationship exists even in the standard orthopaedic books, with various authors labeling it as isosceles, equilateral or a different triangle, without any citation to back this statement. The knowledge of the three bony points relationship in elbow was verified after a survey of orthopaedic surgeons undertaken by the senior author, produced disparate answers. Most (63%) classified this as an isosceles triangle. To clarify this further, 200 elbows were prospectively evaluated to measure the distances between these points and the angles were calculated. Our observations indicate that this triangle is neither isosceles, nor equilateral, but a scalene triangle of unequal sides. There may even be a minimal difference in the 2 sides of the same individual, which has the potential to complicate routine comparison of the two elbows during examination. The analysis of data revealed that all surgeons were aware of the three bony points relationship; however 21 of the 179 (mostly senior surgeons) did not give too much importance to this evaluation in daily clinical practice. Nine surgeons were not sure what type of triangle was formed, 17 thought it was an equilateral triangle, 40 thought it was some other type of triangle while 113 (63%) thought these points formed an isosceles triangle. This is a reflection of the disparity in the perception about this triangle in the orthopaedic community in general.


Bridging May Increase the Risk of Symptomatic Intracranial Hemorrhage in Thrombectomy Patients With Low Alberta Stroke Program Early Computed Tomography Score.
Whether intravenous thrombolysis (IVT) increases the risk for symptomatic intracranial hemorrhage (sICH) in patients treated with mechanical thrombectomy (MT) is a matter of debate. Purpose of this study was to evaluate the extent of early ischemia as a possible factor influencing the risk for sICH after IVT+MT versus direct MT. An explorative analysis of the BEYOND-SWIFT (Bernese-European Registry for Ischemic Stroke Patients Treated Outside Current Guidelines With Neurothrombectomy Devices Using the SOLITAIRE FR With the Intention for Thrombectomy) multicenter cohort was performed. We hypothesized that the sICH risk between IVT+MT versus direct MT differs across the strata of Alberta Stroke Program Early CT Scores (ASPECTS). For this purpose, all patients with ICA, M1, and M2 vessel occlusions and available noncontrast computed tomography or diffusion-weighed imaging ASPECTS (n=2002) were analyzed. We used logistic regression analysis in subgroups, as well as interaction terms, to address the risk of sICH in IVT+MT versus direct MT patients across the ASPECTS strata. In 2002 patients (median age, 73.7 years; 50.7% women; median National Institutes of Health Stroke Scale score, 16), the overall rate of sICH was 6.5% (95% CI, 5.5%-7.7%). Risk of sICH differed across ASPECTS groups (9-10: 6.3%; 6-8: 5.6% and ≤5 9.8%; P=0.042). With decreasing ASPECTS, the risks of sICH in the IVT+MT versus the direct MT group increased from adjusted odds ratio of 0.61 ([95% CI, 0.24-1.60] ASPECTS 9-10), to 1.72 ([95% CI, 0.69-4.24] ASPECTS 6-8) and 6.31 ([95% CI, 1.87-21.29] ASPECTS ≤5), yielding a positive interaction term (1.91 [95% CI, 1.01-3.63]). Sensitivity analyses regarding diffusion-weighed imaging versus noncontrast computed tomography ASPECTS did not alter the primary observations. The extent of early ischemia may influence relative risks of sICH in IVT+MT versus direct MT patients, with an excess sICH risk in IVT+MT patients with low ASPECTS. If confirmed in post hoc analyses of randomized controlled trial data, IVT may be administered more carefully in patients with low ASPECTS eligible for and with direct access to MT.


[Acute acalculous cholecystitis secondary to immersion asphyxia. Implications in organ donation].
A case of acute acalculous cholecystitis in a two year-old girl that undergone drowning in sweet water is reported. Cerebral death was diagnosed and the organs donation was authorized. A biliary peritonitis secondary to gallbladder perforation was met during organs extraction. The liver was rejected.


Left atrial passive emptying function is preserved in patients with permanent atrial fibrillation--a 320-slice multidetector computed tomography study.
Left atrial (LA) mechanical function is thought to be virtually inexistent in patients with permanent atrial fibrillation (AF). Due to recent advances in multidetector computed tomography (MDCT) technology, it is now possible to acquire images of the entire heart in a single heartbeat. The objective of this study was to compare individual components of LA function assessed by MDCT in patients with permanent AF and patients in sinus rhythm (SR). 320-slice MDCT was performed in 30 patients with permanent AF. Measurements of LA volumes during the cardiac cycle were compared to 30 patients in SR, who were matched with respect to age, sex, left ventricular ejection fraction and body surface area. LA volumes were significantly larger in patients with AF than SR patients at all times during the cardiac cycle (LA maximal volume; 82 vs. 55 ml/m(2), p < 0.0001, LA minimal volume; 71 vs. 30 ml/m(2), p < 0.0001). However, except for the absence of active LA emptying, the overall trend of the LA time-volume curve was similar in patients with AF and SR. Compared to SR patients, patients with permanent AF have significantly increased LA volumes throughout the cardiac cycle. Yet, a residual hemodynamic role of LA function may be maintained during permanent AF.


The alternative respiratory pathway is involved in brassinosteroid-induced environmental stress tolerance in Nicotiana benthamiana.
Brassinosteroids (BRs), plant steroid hormones, play essential roles in modulating cell elongation, vascular differentiation, senescence, and stress responses. However, the mechanisms by which BRs regulate plant mitochondria and resistance to abiotic stress remain largely unclear. Mitochondrial alternative oxidase (AOX) is involved in the plant response to a variety of environmental stresses. In this report, the role of AOX in BR-induced tolerance against cold, polyethylene glycol (PEG), and high-light stresses was investigated. Exogenous applied brassinolide (BL, the most active BR) induced, while brassinazole (BRZ, a BR biosynthesis inhibitor) reduced alternative respiration and AOX1 expression in Nicotiana benthamiana. Chemical scavenging of H2O2 and virus-induced gene silencing (VIGS) of NbRBOHB compromised the BR-induced alternative respiratory pathway, and this result was further confirmed by NbAOX1 promoter analysis. Furthermore, inhibition of AOX activity by chemical treatment or a VIGS-based approach decreased plant resistance to environmental stresses and compromised BR-induced stress tolerance. Taken together, our results indicate that BR-induced AOX capability might contribute to the avoidance of superfluous reactive oxygen species accumulation and the protection of photosystems under stress conditions in N. benthamiana.


Experimental study of the combined effect of leukeran, degranol and predisolone.
The effect of the combined treatment with leukeran, degranol and prednisolone on the lymphoid tissue and marrow hamopoiesis in rats is studied. The simultaneous administration of these drugs is shown to cause a more effective inhibition of the lymphoid tissue and a less suppression of the marrow, as compared with their separate administration.


[Evaluation of Non-Pharmaceutical Interventions for Reducing Contact Rate in COVID-19 Pandemic: R0 Estimation and Modeling for Istanbul].
After the declaration of the coronavirus-2019 (COVID-19) pandemic and the detection of the COVID-19 case in Turkey, a series of non-pharmaceutical measures were implemented to reduce the number of contacts at the national level. The aim of this study was to determine the change in the epidemic reproduction rate (R0) with non-pharmaceutical interventions including curfews starting with the first reported case in Istanbul and to evaluate the effectiveness of interventions by estimating the number of cases and deaths using a dynamic compartmental model. While keeping transmission probability (beta) as 3% and incubation period as seven days, we developed five scenarios that represented nonpharmaceutical interventions The first scenario was "if nothing was done" and the last scenario was "curfew". The contact matrix of 16 age-groups created by Prem et al. was used in the study as the contact matrix of "if nothing was done" as scenario 1. For all other scenarios (2-5) contact matrices assumptions were created and R0 values were calculated for the whole of Istanbul according to age groups for all five scenarios. For each scenario, "the number of cases and COVID-related deaths" for one year from the day the first case was detected were calculated with the mathematical modeling method. In the absence of any intervention, R0 value was estimated as 2.86 in Istanbul. Among age-groups, the largest R0 value was observed in ages 15-19, 10-14, 5-9, 20-24 and the values were 5.22, 4.37, 3.32, and 3.33; respectively. Due to school closings and flexible work hours, R0 values decreased to 2.02, 1.84, 1.63 and 1.85 in the same age-groups. With the addition of a curfew for the population under the age of 20 to the above measures, the R0 values for all age groups were reduced to less than one. When R0 values for Istanbul was 2.86 and 1.55 based on our model results, the number of cases and deaths per year were determined as approximately 14 million and 2 million and 2.5 million and 327.000, respectively. School closures were determined as the most effective non-pharmaceutical intervention. Non-pharmaceutical measures with the addition of curfews under the age of 20 and over the age of 65 to the school closings and flexible working hours were identified as effective methods in controlling the COVID-19 epidemic in Istanbul. While the results of this study may not reflect real life data, it has the potential of helping public health policy makers to decide on which non-pharmaceutical interventions are the most effective.


Cancer and the 'other' noncommunicable chronic diseases in older people living with HIV/AIDS in resource-limited settings: a challenge to success.
There is considerable research around the morbidity and mortality related to noncommunicable diseases (NCDs), particularly cardiovascular disease and diabetes, among people living with HIV/AIDS (PLWHA) in resource-richer settings. Less is known about the burden and appropriate management of NCDs, particularly 'other' NCDs including cancer, renal, pulmonary, neurocognitive and mental health conditions, among older PLWHA in resource-limited settings (RLSs). We undertook a literature review of these other NCDs to explore what is currently known about them and identify areas of further research. Systematic literature review of published manuscripts and selected conference abstracts and reports. Although there is growing recognition of the importance of these NCDs among the aging population of PLWHA in RLSs, significant gaps remain in understanding the epidemiology and risk factors among older PLWHA in these settings. Even more concerning is the limited available evidence for effective and feasible approaches to prevention, screening and treatment of these conditions. The burden of these NCDs is related to both the aging of the population of PLWHA and an increased risk due to HIV infection, other comorbidities associated with HIV infection or transmission risk and underlying risk factors in the general community. Results from resource-richer settings and RLSs highlight malignancies, neurocognitive and mental health as well as renal disease as the most significant challenges currently and likely to increase in the future. Although some lessons can be taken from the growing experience with NCDs in older PLWHA in resource-richer settings, additional research is needed to better understand their risk and impact and identify optimal models of care to effectively address this challenge in the areas where the majority of older PLWHA will be receiving care.


On the use of multiple imputation to address data missing by design as well as unintended missing data in case-cohort studies with a binary endpoint.
Case-cohort studies are conducted within cohort studies, with the defining feature that collection of exposure data is limited to a subset of the cohort, leading to a large proportion of missing data by design. Standard analysis uses inverse probability weighting (IPW) to address this intended missing data, but little research has been conducted into how best to perform analysis when there is also unintended missingness. Multiple imputation (MI) has become a default standard for handling unintended missingness and is typically used in combination with IPW to handle the intended missingness due to the case-control sampling. Alternatively, MI could be used to handle both the intended and unintended missingness. While the performance of an MI-only approach has been investigated in the context of a case-cohort study with a time-to-event outcome, it is unclear how this approach performs with a binary outcome. We conducted a simulation study to assess and compare the performance of approaches using only MI, only IPW, and a combination of MI and IPW, for handling intended and unintended missingness in the case-cohort setting. We also applied the approaches to a case study. Our results show that the combined approach is approximately unbiased for estimation of the exposure effect when the sample size is large, and was the least biased with small sample sizes, while MI-only and IPW-only exhibited larger biases in both sample size settings. These findings suggest that a combined MI/IPW approach should be preferred to handle intended and unintended missing data in case-cohort studies with binary outcomes.


Discrepancies in identification of left atrial enlargement using left atrial volume versus left atrial-to-aortic root ratio in dogs.
Left atrial size is prognostically important in dogs with myxomatous mitral valve disease (MMVD). To compare the level of agreement in identification of left atrial enlargement (LAE) between the left atrial-to-aortic root ratio (LA : Ao) and left atrial volume using the biplane area-length method indexed to body weight (LA Vol/BW). Sixty dogs with MMVD and 22 normal dogs were prospectively studied with 2-dimensional echocardiography. The upper limit of normal for LA Vol/BW was defined as 1.1 mL/kg. LA : Ao was deemed normal if ≤1.5. To define overall disease severity, each dog was assigned a mitral regurgitation severity score (MRSS) based on echocardiographic parameters that did not include left atrial size. ACVIM staging also was utilized. Of 60 affected dogs, 20 were ACVIM Stage B1, 25 were Stage B2, and 15 were Stage C. LA Vol/BW identified LAE in 12 cases in which LA : Ao was normal; 7 of these were Stage B1 and 5 were Stage B2. This diagnostic disagreement was significant (P = .00012). Of the 12 cases in which diagnostic discrepancies were identified, 5/5 of the B2 dogs and 3/7 B1 dogs had a moderate MRSS, whereas 4/7 B1 dogs had a mild MRSS. No diagnostic discrepancies between LA : Ao and LA Vol/BW were apparent in dogs with a severe MRSS. This study shows evidence of diagnostic disagreement between LA : Ao and LA Vol/BW for assessment of LAE. LA Vol/BW may be superior to LA : Ao for identification of mild LAE.


Aln2tbl: building a mitochondrial features table from a assembly alignment in fasta format.
The sequencing, annotation and analysis of complete mitochondrial genomes is an important research tool in phylogeny and evolution. Starting with the primary sequence, genes/features are generally annotated automatically to obtain preliminary annotations in the form of a feature table. Further manual curation in a graphic alignment editor is nevertheless necessary to revise annotations. As such, the automatically generated feature table is invalidated and has to be modified manually before submission to data banks. We developed aln2tbl.py, a python script that recreates a feature table from a manually refined alignment of genes mapped on the mitochondrial genome in fasta format. The feature table is populated with notes and annotations specific to mitochondrial genomes. The table can be used to create a sqn file to be submitted directly to data banks. In summary, our scripts fills one gap in the available toolbox and, combined with other software, allows the automation of the entire process, from primary sequence to annotated genome submission, even if a manual curation step is conducted in a visual sequence editor.


Disparate peroxisome-related defects in Arabidopsis pex6 and pex26 mutants link peroxisomal retrotranslocation and oil body utilization.
Catabolism of fatty acids stored in oil bodies is essential for seed germination and seedling development in Arabidopsis. This fatty acid breakdown occurs in peroxisomes, organelles that sequester oxidative reactions. Import of peroxisomal enzymes is facilitated by peroxins including PEX5, a receptor that delivers cargo proteins from the cytosol to the peroxisomal matrix. After cargo delivery, a complex of the PEX1 and PEX6 ATPases and the PEX26 tail-anchored membrane protein removes ubiquitinated PEX5 from the peroxisomal membrane. We identified Arabidopsis pex6 and pex26 mutants by screening for inefficient seedling β-oxidation phenotypes. The mutants displayed distinct defects in growth, response to a peroxisomally metabolized auxin precursor, and peroxisomal protein import. The low PEX5 levels in these mutants were increased by treatment with a proteasome inhibitor or by combining pex26 with peroxisome-associated ubiquitination machinery mutants, suggesting that ubiquitinated PEX5 is degraded by the proteasome when the function of PEX6 or PEX26 is reduced. Combining pex26 with mutations that increase PEX5 levels either worsened or improved pex26 physiological and molecular defects, depending on the introduced lesion. Moreover, elevating PEX5 levels via a 35S:PEX5 transgene exacerbated pex26 defects and ameliorated the defects of only a subset of pex6 alleles, implying that decreased PEX5 is not the sole molecular deficiency in these mutants. We found peroxisomes clustered around persisting oil bodies in pex6 and pex26 seedlings, suggesting a role for peroxisomal retrotranslocation machinery in oil body utilization. The disparate phenotypes of these pex alleles may reflect unanticipated functions of the peroxisomal ATPase complex.


The 2.2 A resolution crystal structure of influenza B neuraminidase and its complex with sialic acid.
Influenza virus neuraminidase catalyses the cleavage of terminal sialic acid, the viral receptor, from carbohydrate chains on glycoproteins and glycolipids. We present the crystal structure of the enzymatically active head of influenza B virus neuraminidase from the strain B/Beijing/1/87. The native structure has been refined to a crystallographic R-factor of 14.8% at 2.2 A resolution and its complex with sialic acid refined at 2.8 A resolution. The overall fold of the molecule is very similar to the already known structure of neuraminidase from influenza A virus, with which there is amino acid sequence homology of approximately 30%. Two calcium binding sites have been identified. One of them, previously undescribed, is located between the active site and a large surface antigenic loop. The calcium ion is octahedrally co-ordinated by five oxygen atoms from the protein and one water molecule. Sequence comparisons suggest that this calcium site should occur in all influenza A and B virus neuraminidases. Soaking of sialic acid into the crystals has enabled the mode of binding of the reaction product in the putative active site pocket to be revealed. All the large side groups of the sialic acid are equatorial and are specifically recognized by nine fully conserved active site residues. These in turn are stabilized by a second shell of 10 highly conserved residues principally by an extensive network of hydrogen bonds.


Salts promote activation of fat cell adenylate cyclase by GTP: special role for sodium ion.
The effects of GTP on adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 22.214.171.124] of human and rat fat cell membranes ("ghosts" and purified membranes) were examined in the absence and presence of added inorganic salts. With human ghosts GTP alone (0.1 mM) inhibited enzyme activity by 40% at 30 degrees C and had no significant effect at 37 degrees C. At both temperatures Na+ salts of Cl-, N3-, and SO2-(4) stimulated activity (up to 4-fold basal activity for 200 mM NaN3), with maximal effects at salt concentrations of 100-200 mM. Over the same concentration range these salts also allowed temperature-dependent stimulation by GTP. GTP increased the maximal activity produced by salt alone by about 2-fold at 30 degrees C and about 4-fold at 37 degrees C. Na+ (added as Cl-) was much more effective than other alkali metal cations in promoting activation by GTP. Na+ salts allowed activation of the human enzyme by the GTP analog 5'-guanylyl imidodiphosphate and also promoted stimulation of rat fat cell adenylate cyclase by both nucleotides. In time course studies of human and rat fat cell ghosts, GTP appeared to sustain an initial high rate of salt-stimulated activity, which in the absence of nucleotide subsequently fell to a lower rate, suggesting that salts might activate adenylate cyclase by promoting the stimulatory effect of endogenous membrane-bound GTP. However, with purified human fat cell membranes and a GTP-free system, salts were still stimulatory and promoted activation by added GTP. These results differ from those of previous reports in other systems in which Na+ has promoted only inhibitory effects in GTP regulation of adenylate cyclase.


High fluoroquinolone MIC is associated with fluoroquinolone treatment failure in urinary tract infections caused by fluoroquinolone susceptible Escherichia coli.
Suboptimal clinical response to fluoroquinolone (FQ) therapy has been clearly documented in patients with Salmonella typhi infection with reduced FQ susceptibility. However, the clinical impact of reduced FQ susceptibility on other infections including E. coli urinary tract infections (UTIs) has never been evaluated. We conducted a retrospective cohort study of female patients with fluoroquinolone susceptible E. coli (FQSEC) UTIs who received FQ therapy at outpatient services within University of Pennsylvania Health System, Philadelphia. Exposed patients were those with high MIC-FQSEC UTIs (the levofloxacin MIC > 0.12 but ≤ 2 mg/L) while unexposed patients were those with low MIC-FQSEC UTIs (the levofloxacin MIC ≤ 0.12 mg/L). The primary treatment outcome was treatment failure within 10 weeks after initiation of FQ therapy. From May 2008 to April 2011, we enrolled 29 exposed patients and 246 unexposed patients. Two patients in each group experienced treatment failure; exposed vs. unexposed (6.9 vs. 0.8%; p = 0.06). Risk difference and risk ratio (RR) for treatment failure were 0.06 [95% CI -0.03-0.15; exact-p = 0.06] and 8.48 [95% CI 1.24-57.97; exact-p = 0.06], respectively. After adjusting for underlying cerebrovascular disease, the RR was 7.12 (95% CI 1.20-42.10; MH-p = 0.04). Our study demonstrated the negative impact of reduced FQ susceptibility on the treatment response to FQ therapy in FQSEC UTIs. This negative impact may be more intensified in other serious infections. Future studies in other clinical situations should be conducted to fill the gap of knowledge.


Indirect enzyme-linked immunosorbent assay (ELISA) for the detection of Coxsackievirus group B antibodies.
An indirect, solid phase, microplate enzyme-linked immunosorbent assay (ELISA) was found to be highly sensitive and reliable for detecting antibodies to the group B Coxsackieviruses and other picornaviruses. Conditions for obtaining maximum sensitivity and reproducibility of the indirect ELISA are described. Antibody titres were comparable to those obtained by the virus neutralization test and over 50 times higher than those obtained by the complement-fixation test. Purified virions used in the indirect ELISA reacted with low levels of cross-reacting heterotypic antibodies elicited by each of the six group B Coxsackieviruses, although homotypic reactions resulted in highest titres.


A Current Overview of Cyclodextrin-Based Nanocarriers for Enhanced Antifungal Delivery.
Fungal infections are an extremely serious health problem, particularly in patients with compromised immune systems. Most antifungal agents have low aqueous solubility, which may hamper their bioavailability. Their complexation with cyclodextrins (CDs) could increase the solubility of antifungals, facilitating their antifungal efficacy. Nanoparticulate systems are promising carriers for antifungal delivery due to their ability to overcome the drawbacks of conventional dosage forms. CD-based nanocarriers could form beneficial combinations of CDs and nanoparticulate platforms. These systems have synergistic or additive effects regarding improved drug loading, enhanced chemical stability, and enhanced drug permeation through membranes, thereby increasing the bioavailability of drugs. Here, an application of CD in antifungal drug formulations is reviewed. CD-based nanocarriers, such as nanoparticles, liposomes, nanoemulsions, nanofibers, and in situ gels, enhancing antifungal activity in a controlled-release manner and possessing good toxicological profiles, are described. Additionally, the examples of current, updated CD-based nanocarriers loaded with antifungal drugs for delivery by various routes of administration are discussed and summarized.


Links Between Sexual Orientation and Disclosure Among Black MSM: Sexual Orientation and Disclosure Matter for PrEP Awareness.
The HIV epidemic in the United States has disproportionately burdened Black men who have sex with men (MSM), particularly in the South. While pre-exposure prophylaxis (PrEP) has high demonstrated efficacy, uptake is low among Black MSM. We utilized a sample of 345 HIV-negative or unknown HIV status Black MSM from Atlanta, Georgia. Bivariate and multivariable logistic regression models examined the effects of sexual orientation and disclosure on PrEP awareness and use. Despite the majority of the sample reporting PrEP awareness (91%), few Black MSM in our sample had ever used PrEP (10%). Bisexual Black MSM were less likely to have been aware of PrEP compared to their same-gender loving/gay counterparts. Black MSM who had disclosed their sexual orientation to some or all of the members of their networks were more aware of PrEP compared to their counterparts who reported lower levels of disclosure, but were not more likely to actually use PrEP. Alarmingly, the gap in PrEP awareness and use has not decreased over the past 5 years. These findings suggest that disclosure may be a relevant characteristic to consider for PrEP awareness, but there may be more to consider in closing the awareness-uptake gap among Black MSM.


Global Initiative for Childhood Cancer: progress and challenges in Panama.
Despite being classified as a high-income country, Panama still faces challenges in providing care for children and adolescents with cancer. Annually, 170 new cases of childhood cancer are diagnosed in Panama, and the survival rate is around 60%. To improve this, the establishment of a Pediatric Cancer Commission comprised of healthcare professionals and nonprofit organizations has been a critical step toward the objectives outlined in the CureAll framework of the World Health Organization Global Initiative for Childhood Cancer (GICC). To improve childhood cancer care in Panama, a workshop for cancer in children and adolescents was conducted with the support of St. Jude Children's Research Hospital, Children's Hospital Colorado, the Ministry of Health of Panama, and the Pan American Health Organization. The commissions established were on: Nursing, Palliative Care, Psychosocial, Hospital Registry, Early Diagnosis, and Health Services. Each commission has a specific project to be implemented in the period 2021-2029 to continue the progress toward improving childhood cancer care. Since the start of implementation of the GICC in Panama, important achievements have included the launch in 2021 of the Guide for the Diagnosis of Cancer in Children and Adolescents, and training programs for primary care health personnel. Through these programs, more than 1 000 health professionals have been trained on diagnosis of cancer in childhood and adolescence. Challenges remain, such as access to quality care, and it is essential to continue efforts to improve childhood cancer care.


Parasite communities and feeding ecology of the European sprat (Sprattus sprattus L.) over its range of distribution.
The metazoan parasite fauna and feeding ecology of 165 Sprattus sprattus (L., 1758) was studied from different geographic regions (Baltic Sea, North Sea, English Channel, Bay of Biscay, Mediterranean Sea). A total of 13 metazoan parasite species were identified including six Digenea, one Monogenea, two Cestoda, two Nematoda and two Crustacea. Didymozoidae indet., Lecithocladium excisum and Bomolochidae indet. represent new host records. The parasite species richness differed according to regions and ranged between 3 and 10. The most species-rich parasite fauna was recorded for sprats from the Bay of Biscay (North Atlantic), and the fishes from the Baltic Sea contained the lowest number of parasite species. More closely connected geographical regions, the North Sea, English Channel and Bay of Biscay, showed more similar parasite component communities compared with more distant regions. From the examined stomachs of S. sprattus, a total of 11 different prey items were identified, including Mollusca, Annelida, Crustacea and Tunicata. The highest number of prey organisms belonged to the crustaceans. The variety of prey items in the stomach was reflected by the parasite community differences and parasite species richness from the different regions. The feeding ecology of the fish at the sampled localities was responsible for the observed parasite composition and, secondarily, the zoogeographical distribution of the parasites, questioning the use of the recorded sprat parasites as biological indicators for environmental conditions and change.


Radioactive iodine therapy for goitrous Hashimoto's thyroiditis.
Hashimoto's thyroiditis is an autoimmune disease that can produce marked clinical symptoms when patients have large diffuse goiters. This retrospective cohort study was designed to evaluate whether radioactive iodine (RAI) is effective for Hashimoto's thyroiditis with a large goiter. Starting in November 1999, 13 Hashimoto's patients with large goiters, whose thyroiditis was refractory to TSH suppression therapy with thyroid hormone administration [two men and 11 women with a mean age of 61.2 +/- 8.9 yr (50-79 yr)], were recruited for the present study. The duration of symptomatic goiter before undergoing RAI was 12.0 +/- 7.9 yr (4-33 yr). Thirteen millicuries of 131I was administered two to six times, at an interval of 1-6 months on an outpatient basis. Thyroid weight was measured ultrasonographically, or by computed tomography if ultrasound was not possible due to the large size of the goiter. RAI was administered an average of 4.7 +/- 1.4 times (two to six times), with a total dose of 59.8 +/- 17.3 mCi (25.0-78.0 mCi). The observation period was 47.9 +/- 13.4 months (26-66 months) after the first RAI. The average weight of the thyroid gland was 125.3 +/- 57.7 g (42.9-269.4 g) before the first RAI, decreasing significantly to 49.7 +/- 25.8 g (18.3-93.3 g) after the last RAI (P < 0.001, paired Student's t test). The percent reduction from baseline was 58.7 +/- 14.2% (35.7-84.0%). None of the patients showed an increase in goiter size or complained of a pressure sensation after any of the RAI treatments. RAI is effective in Hashimoto's thyroiditis with a large goiter.