Trends in cost and consumption of essential medicines for non-communicable diseases in Azerbaijan, Georgia, and Uzbekistan, from 2019 to 2021.
Access to medicines is a global priority. Azerbaijan, Georgia, and Uzbekistan have different approaches to pricing policies for pharmaceuticals. The aim of this study was to analyze recent trends in the consumption and prices of non-communicable disease (NCD) medicines in Azerbaijan, Georgia, and Uzbekistan, in the outpatient setting. We included medicines for asthma and COPD, cancer, cardiovascular disease, diabetes, epilepsy, and mental disorders. Sales data for pharmaceutical products in community pharmacies were extracted from a commercial database. Changes in consumption and prices were analyzed across all included NCD medicines, by disease category and pharmacological group. Consumption of NCD medicines was highest in Georgia, at twice the levels in Azerbaijan, and four times levels in Uzbekistan. Average prices of NCD medicines, weighted by consumption, increased by 26% in Georgia, but decreased by 3% in Azerbaijan and by 0.1% in Uzbekistan. Prices increased for all disease groups in Georgia (from +13% for epilepsy medicines to +86% for cancer), varied by group in Uzbekistan (from -22% for epilepsy medicines to +47% for cancer), while changes in Azerbaijan were smaller in magnitude (from -4% for medicines for cardiovascular disease to +11% for cancer). Cancer medicines had markedly higher prices in Uzbekistan, and asthma and COPD medicines had markedly higher prices in Azerbaijan and Uzbekistan. Georgia showed the highest outpatient consumption of NCD medicines, suggesting the broadest access to treatment. However, Georgia also saw marked price increases, greater than in the other countries. In Georgia, where there was no price regulation, widespread price increases and increases in consumption both contribute to increasing pharmaceutical expenditures. In Azerbaijan and Uzbekistan, increases in outpatient pharmaceutical expenditures were primarily driven by increases in consumption, rather than increases in price. Comparing trends in consumption and pricing can identify gaps in access and inform future policy approaches.


Is phlorizin or its aglycon the inhibitor of intestinal glucose transport? A study in normal and lactase deficient man.
Inhibition of glucose transport by phlorizin was examined in man by perfusion of an isolated small bowel segment. Inhibition was similar in normal and lactase deficient subjects. Since the small bowel of lactase deficient subjects contains only very small amounts of phlorizin hydrolase, phlorizin and not a product of enzymatic cleavage is the inhibitor of the small intestinal glucose carrier.


Twelve quick tips for designing sound dynamical models for bioprocesses.
Because of the inherent complexity of bioprocesses, mathematical models are more and more used for process design, control, optimization, etc. These models are generally based on a set of biochemical reactions. Model equations are then derived from mass balance, coupled with empirical kinetics. Biological models are nonlinear and represent processes, which by essence are dynamic and adaptive. The temptation to embed most of the biology is high, with the risk that calibration would not be significant anymore. The most important task for a modeler is thus to ensure a balance between model complexity and ease of use. Since a model should be tailored to the objectives, which will depend on applications and environment, a universal model representing any possible situation is probably not the best option.


Developing Cognitive Task Analysis-based Educational Videos for Basic Surgical Skills in Plastic Surgery.
To describe the development of cognitive task analysis (CTA)-based multimedia educational videos for surgical trainees in plastic surgery. A needs assessment survey was used to identify 5 plastic surgery skills on which to focus the educational videos. Three plastic surgeons were video-recorded performing each skill while describing the procedure, and were interviewed with probing questions. Three medical student reviewers coded transcripts and categorized each step into "action," "decision," or "assessment," and created a cognitive demands table (CDT) for each skill. The CDTs were combined into 1 table that was reviewed by the surgeons performing each skill to ensure accuracy. The final CDTs were compared against each surgeon's original transcripts. The total number of steps identified, percentage of steps shared, and the average percentage of steps omitted were calculated. Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada, an urban tertiary care teaching center. Canadian junior plastic surgery residents (n = 78) were sent a needs assessment survey. Four plastic surgeons and 1 orthopedic surgeon performed the skills. Twenty-eight residents responded to the survey (36%). Subcuticular suturing, horizontal and vertical mattress suturing, hand splinting, digital nerve block, and excisional biopsy had the most number of residents (>80%) rank the skills as being skills that students should be able to perform before entering residency. The number of steps identified through CTA ranged from 12 to 29. Percentage of steps shared by all 3 surgeons for each skill ranged from 30% to 48%, while the average percentage of steps that were omitted by each surgeon ranged from 27% to 40%. Instructional videos for basic surgical skills may be generated using CTA to help experts provide comprehensive descriptions of a procedure. A CTA-based educational tool may give trainees access to a broader, objective body of knowledge, allowing them to learn decision-making processes before entering the operating room.


Understanding the Impact of Population and Cancer Type on Tumor Mutation Burden Scores: A Comprehensive Whole-Exome Study in Cancer Patients From India.
The purpose of this study was to understand the impact of population diversity and geographic variation on tumor mutation burden (TMB) scores across cancers and its implication on stratification of patients for immune checkpoint inhibitor (ICI) therapy. This retrospective study used whole-exome sequencing (WES) to profile 1,233 Indian patients with cancer across 30 different cancer types and to estimate their TMB scores. A WES-based pipeline was adopted, along with an indigenously developed strategy for arriving at true somatic mutations. A robust unsupervised machine learning approach was used to understand the distribution of TMB scores across different populations and within the population. The results of the study showed a biphasic distribution of TMB scores in most cancers, with different threshold scores across cancer types. Patients with cancer in India had higher TMB scores compared with the Caucasian patients. We also observed that the TMB score value at 90th percentile (predicting high efficacy to ICI) was high in four different cancer types (sarcoma, ovary, head and neck, and breast) in the Indian cohort as compared with The Cancer Genome Atlas or public cohort. However, in lung and colorectal cancers, the TMB score distribution was similar between the two population cohorts. The findings of this study indicate that it is crucial to benchmark both cancer-specific and population-specific TMB distributions to establish a TMB threshold for each cancer in various populations. Additional prospective studies on much larger population across different cancers are warranted to validate this observation to become the standard of care.


A systematic approach to a self-generating fuzzy rule-table for function approximation.
In this paper, a systematic design is proposed to determine fuzzy system structure and learning its parameters, from a set of given training examples. In particular, two fundamental problems concerning fuzzy system modeling are addressed: 1) fuzzy rule parameter optimization and 2) the identification of system structure (i.e., the number of membership functions and fuzzy rules). A four-step approach to build a fuzzy system automatically is presented: Step 1 directly obtains the optimum fuzzy rules for a given membership function configuration. Step 2 optimizes the allocation of the membership functions and the conclusion of the rules, in order to achieve a better approximation. Step 3 determines a new and more suitable topology with the information derived from the approximation error distribution; it decides which variables should increase the number of membership functions. Finally, Step 4 determines which structure should be selected to approximate the function, from the possible configurations provided by the algorithm in the three previous steps. The results of applying this method to the problem of function approximation are presented and then compared with other methodologies proposed in the bibliography.


Review of Treatment and Prognosis of Stage IVB Cervical Carcinoma.
In most patients, stage IVB cervical cancer is incurable, and the outcomes are poor. There is significant individual variation in patients with stage IVB cervical cancer, in whom standard treatment has not been well defined. This study aims to review the outcomes and discuss treatment strategies in patients with stage IVB cervical cancer. From January 1, 1992, to December 31, 2011, we retrospectively reviewed the data of patients with stage IVB cervical cancer who were given a diagnosis at the Department of Gynecology of the Cancer Institute Hospital. A total of 111 patients were enrolled. At the time of analysis, the median overall survival (OS) was 16.6 months (range, 0.2-120.9 months), and the 5-year OS rate was 20.2%. The 5-year OS rate was 59.4% for those with only para-aortic lymph node metastases; 24.8% for those with lymphogenous metastases, excluding those with only para-aortic lymph node metastases; 6.1% for those with hematogenous metastases; and 0% for those with disseminated metastases. The OS in patients with lymphogenous metastases was better compared with that of those with either hematogenous or disseminated metastases (P < 0.0001). In multivariate analysis, the performance status, site of metastases (only lymph node or other metastases), and local stage were all independent prognostic factors. We determined performance status, site of metastases (only lymph node or other metastases), and local stage as independent prognostic factors in patients with stage IVB cervical cancer. Regarding treatment, we confirmed that the effectiveness of chemotherapy was also of significance.


Cutaneous tumoural melanosis: a presentation of complete regression of cutaneous melanoma.
Partial regression is common in cutaneous melanoma; however, complete regression manifesting as tumoural melanosis is rare, conceptually challenging and under-reported. In this study we report on clinical, histological and molecular findings in four cases of completely regressed cutaneous melanoma with nodal or brain metastasis, followed by a comprehensive review of the literature. Our series included three women and one man with an average age of 60 years, and clinical presentation with hyper-pigmented cutaneous lesions. The main histological findings were expansile aggregates of melanophages with complete absence of malignant melanocytes on microscopic and immunohistochemical examination of the entire primary skin lesions, as well as substantial reduction in the number of junctional melanocytes in the overlying epidermis. NRAS mutant/BRAF wild type metastatic deposits were identified in three patients, with one patient having a BRAF V600E mutant metastatic tumour. Tumoural melanosis likely represents a partially effective immunological response to melanoma, with complete eradication of cutaneous disease and less effective systemic results. Patients with tumoural melanosis should be managed as potential completely regressed cutaneous melanoma, with comprehensive physical examination, imaging work up and close follow up.


Self-repelling bipedal exploration process.
A self-repelling two-leg (biped) spider walk is considered where the local stochastic movements are governed by two independent control parameters β_{d} and β_{h}, so that the former controls the distance (d) between the legs positions, and the latter controls the statistics of self-crossing of the traversed paths. The probability measure for local movements is supposed to be the one for the "true self-avoiding walk" multiplied by a factor exponentially decaying with d. After a transient behavior for short times, a variety of behaviors have been observed for large times depending on the value of β_{d} and β_{h}. Our statistical analysis reveals that the system undergoes a crossover between two (small and large β_{d}) regimes identified in large times (t). In the small β_{d} regime, the random walkers (identified by the position of the legs of the spider) remain on average in a fixed nonzero distance in the large time limit, whereas in the second regime (large β_{d}), the absorbing force between the walkers dominates the other stochastic forces. In the latter regime, d decays in a power-law fashion with the logarithm of time. When the system is mapped to a growth process (represented by a height field which is identified by the number of visits for each point), the roughness and the average height show different behaviors in two regimes, i.e., they show a power law with respect to t in the first regime and logt in the second regime. The fractal dimension of the random walker traces and the winding angle are shown to consistently undergo a similar crossover.


Spatial structure and pH-dependent conformational diversity of dimeric transmembrane domain of the receptor tyrosine kinase EphA1.
Eph receptors are found in a wide variety of cells in developing and mature tissues and represent the largest family of receptor tyrosine kinases, regulating cell shape, movements, and attachment. The receptor tyrosine kinases conduct biochemical signals across plasma membrane via lateral dimerization in which their transmembrane domains play an important role. Structural-dynamic properties of the homodimeric transmembrane domain of the EphA1 receptor were investigated with the aid of solution NMR in lipid bicelles and molecular dynamics in explicit lipid bilayer. EphA1 transmembrane segments associate in a right-handed parallel alpha-helical bundle, region (544-569)(2), through the N-terminal glycine zipper motif A(550)X(3)G(554)X(3)G(558). Under acidic conditions, the N terminus of the transmembrane helix is stabilized by an N-capping box formed by the uncharged carboxyl group of Glu(547), whereas its deprotonation results in a rearrangement of hydrogen bonds, fractional unfolding of the helix, and a realignment of the helix-helix packing with appearance of additional minor dimer conformation utilizing seemingly the C-terminal GG4-like dimerization motif A(560)X(3)G(564). This can be interpreted as the ability of the EphA1 receptor to adjust its response to ligand binding according to extracellular pH. The dependence of the pK(a) value of Glu(547) and the dimer conformational equilibrium on the lipid head charge suggests that both local environment and membrane surface potential can modulate dimerization and activation of the receptor. This makes the EphA1 receptor unique among the Eph family, implying its possible physiological role as an "extracellular pH sensor," and can have relevant physiological implications.


Do Current Measures of Polygenic Risk for Mental Disorders Contribute to Population Variance in Mental Health?
The polygenic risk score (PRS) allows for quantification of the relative contributions of genes and environment in population-based studies of mental health. We analyzed the impact of transdiagnostic schizophrenia PRS and measures of familial and environmental risk on the level of and change in general mental health (Short-Form-36 mental health) in the Netherlands Mental Health Survey and Incidence Study-2 general population sample, interviewed 4 times over a period of 9 years, yielding 8901 observations in 2380 individuals. Schizophrenia PRS, family history, somatic pain, and a range of environmental risks and social circumstances were included in the regression model of level of and change in mental health. We calculated the relative contribution of each (group of) risk factor(s) to the variance in (change in) mental health. In the combined model, familial and environmental factors explained around 17% of the variance in mental health, of which around 5% was explained by age and sex, 30% by social circumstances, 16% by pain, 22% by environmental risk factors, 24% by family history, and 3% by PRS for schizophrenia (PRS-SZ). Results were similar, but attenuated, for the model of mental health change over time. Childhood trauma and gap between actual and desired social status explained most of the variance. PRS for bipolar disorder, cross-disorder, and depression explained less variance in mental health than PRS-SZ. Polygenic risk for mental suffering, derived from significance-testing in massive samples, lacks impact in analyses focusing on prediction in a general population epidemiological setting. Social-environmental circumstances, particularly childhood trauma and perceived status gap, drive most of the attributable variation in population mental health.


Laparoscopic rectopexy for solitary rectal ulcer syndrome without overt rectal prolapse: a case report and review of the literature.
Solitary rectal ulcer syndrome is a rare clinical entity. Several treatment options has been described. However, there is no consensus yet on treatment algorithm and standard surgical procedure. Rectopexy is one of the surgical options and it is generally performed in patients with solitary rectal ulcer accompanied with overt prolapse. Various outcomes have been reported for rectopexy in the patients with occult prolapse or rectal intussusception. In the literature; outcomes of laparoscopic non-resection rectopexy procedure have been reported in the limited number of case or case series. No study has emphasized the outcomes of laparoscopic non-resection rectopexy procedure in the patients with solitary rectal ulcer without overt prolapse. In this report we aimed to present clinical outcomes of laparoscopic non-resection posterior suture rectopexy procedure in a 21-year-old female patient with solitary rectal ulcer without overt prolapse.


An investigation into the cause of orientation-sensitivity in haptic object recognition.
Object orientation influences visual and haptic recognition differently. This could be caused by the two modalities accessing different object representations or it could be due to differences in how each modality acquires information. These two alternatives were investigated using sequential haptic matching tasks. Matches presented the same object twice. Mismatches presented two similarly-shaped objects. Objects were either both placed at the same orientation or were rotated 90° in depth from each other. Experiment 1 manipulated exploration time to test if longer durations weakened orientation-sensitivity by allowing orientation-invariant representations to be extracted. This hypothesis was not supported. Experiment 2 investigated whether the same-orientation advantage resulted from general spatial or motor action cueing rather than the involvement of orientation-specific object representations. To distinguish between these two possibilities, people did a secondary task interleaved within the matching task. They reported the orientation of a fork or spoon which was presented in between the first and second objects. The main axis of the fork/spoon was the same as that of the final object, equating spatial and motor cueing across the same-orientation and orientation-change conditions. Nevertheless, matching remained orientation-sensitive. Together these results suggest that there are separate visual and haptic stored, orientation-specific perceptual representations of objects.


Synthesis of a family of solids through the building-block approach: a case study with Ag(+) substitution in the ternary Na-Ge-Se system.
A new family of Ag-substituted pseudoquaternary alkali-seleno-germanates has been synthesized by two solid-state routes: the conventional flux method and metathesis. This family includes a series of semiconductors with varying amounts of Ag+ substituted for Na+ in Na8Ge4Se10 to form AgxNa(8-x)Ge4Se10, [x = 0.31 (I), 0.67 (II), 0.77 (III), 0.87 (IV), 1.05 (V), 1.09 (VI)] and another phase with a different composition AgxNa(6-x)Ge2Se7 (x = 1.76), VII, related to Na6Ge2Se7. In I-VI, Ge4Se10(8-) constitutes a 6-membered chairlike unit with a Ge-Ge bond, while in VII, a corner-shared dimer of GeSe4 tetrahedra (Ge2Se76-) acts as the building unit. The single-crystal structure analysis indicates that there is a phase transition from P to C2/c, in changing from pure Na8Ge4Se10 to AgxNa(8-x)Ge4 Se10 (I-VI), while there is no phase transition between pure Na6Ge2Se7 and AgxNa(6-x)Ge2Se7 (x = 1.76). The structures of I-VI may be described in terms of layers of cubic close-packed Se2- anions. In between the Se layers, octahedral holes fully occupied by Na+ and mixed Ag+/Na+ cations alternate with layers formed of octahedral holes fully occupied by Na+ and Ge26+ cations. Two adjacent Ge26+ cations form a chairlike Ge4Se10(8-) anion in which Ge-Ge bonds are oriented almost parallel to the Se layers. In contrast, VII does not have close-packed anions. Corner-shared GeSe4 tetrahedra (Ge2Se7(6-) dimer) and AgSe4 tetrahedra form layers that are cross-linked by Na/AgSe4 tetrahedra to form a 3-dimensional (3-D) structure. An optical property investigation indicates a red shift in the band gap of AgxNa(8-x)Ge4Se10 (x = 0.67)(II) as compared to that of pure Na8Ge4Se10. Raman data also indicate a red shift of the Ge-Se stretching mode in the Ag+-substituted phase II (x = 0.67) compared to that of Na8Ge4Se10.


[Effect of Type 2 Diabetes on Results of Endovascular Treatment of Ischemic Heart Disease With Drug Covered Stents (Results of 1 Year Follow-up).].
Aim of the study was to determine the impact of sirolimus-eluting stents (SES) on clinical outcomes in patients with type 2 diabetes mellitus (DM) undergoing coronary revascularisation. The study enrolled 99 diabetic patients with de novo lesions in native coronary arteries. Medically treated DM was present in 61 patients (62%), 7 (7%) of whom required insulin. 53 patients received 78 SES and 46 patients received 57 bare metal stents. The differences in clinical outcomes between diabetic patients treated with SES and bare metal stents were assessed. Major adverse cardiac events (MACE) defined as death, myocardial infarction (MI), repeat revascularizations, and recurrences of angina were analyzed at 12-month follow-up. In the SES group the rate of recurrence of angina was 17%, the rate of coronary artery bypass surgery was 3,8%, the rate of repeat coronary angioplasty was 5,7%. In the bare metal stent group the rate of recurrence of angina was 37,8%, the rate of coronary artery bypass surgery was 2,2%, the rate of MI was 4,4%, the rate of repeat coronary angioplasty was 22,2%. Implantation of SES in patients with type 2 diabetes mellitus reduces recurrence of angina and major adverse cardiac events during first year after coronary angioplasty.


Influence of the Calcium Hydroxide Intracanal Dressing on Dentinal Tubule Penetration of Two Root Canal Sealers.
The aim of this study was to evaluate the effect of a calcium hydroxide (CH) dressing on the tubular penetration of two endodontic sealers, AH Plus (Dentsply Maillefer, Ballaigues, Switzerland) and MTA Fillapex (Angelus, Londrina, Brazil). Seventy-two mandibular premolars with a single root canal were prepared with ProFile.04 rotary instruments (Dentsply Maillefer) and divided into four groups. In two groups, an intracanal CH dressing was placed for 15 days. The obturations were performed with lateral condensation of gutta-percha in combination with one of the tested sealers. The roots were transversely sectioned at the apical and middle levels. The percentage of sealer penetration in the root canal walls and the percentage of impregnated dentin area in the transverse sections were obtained using confocal laser scanning microscopy. Statistical analysis was performed using one-way analysis of variance (ANOVA) and Games-Howell test. The CH dressing reduced the mean value of tubular penetration in the middle third of teeth obturated with AH Plus (P<0.01), whereas no difference was observed at the apical sections for both sealers. The CH dressing did not interfere with the apical penetration of both tested sealers, however, decreased the tubular penetration in the middle third of the AH Plus root canal fillings. Overall, MTA Fillapex presented higher tubular penetration than AH Plus obturations.


[Effects of cigarette smoke on phagocytosed function of monocyte-derived macrophage in chronic obstructive pulmonary disease patients].
To explore the effects of cigarette smoke extract (CSE) on phagocytosizing function of monocyte-derived macrophages (MDMs) in patients with chronic obstructive pulmonary disease (COPD). From January 2012 to March 2013, peripheral blood monocytes were isolated from 32 stable COPD patients and 32 healthy controls at First Hospital, Lanzhou University. MDM was induced and cultured from monocytes in vitro. The MDMs from COPD patients and healthy controls were divided into 4 groups of COPD non-CSE (conventional culture), COPD CSE (4% CSE treatment for 6 h), healthy non-CSE (conventional culture) and healthy CSE (4% CSE treatment for 6 h). Flow cytometry (mean fluorescence intensity, MFI) and laser scanning confocal microscopy (fluorescence grey level) were applied to detect the ability of MDM phagocytosed fluorescein-labeled Escherichia coli (FITC-E.coli). Total antioxidative capacity (TAC) was measured by o-phenanthroline colorimetry. Malondialdehyde (MDA) was measured by thiobarbituric acid colorimetry and glutathione peroxidase (GSH-PX) by 5, 5'-dithiobis-2-nitrobenzoic acid (DTNB) method. MFI and fluorescence grey level in COPD non-CSE group (20.2 ± 2.2, 51.5 ± 5.8) significantly decreased than those in healthy non-CSE group (56.9 ± 6.7, 87.3 ± 7.3). And in COPD CSE (7.6 ± 0.7, 14.1 ± 3.4) and healthy CSE groups (48.0 ± 5.4, 69.7 ± 6.0) decreased more than those in COPD non-CSE and healthy non-CSE groups (all P < 0.01). The levels of TAC and GSH-PX in COPD non-CSE group ((4.1 ± 0.5), (47.1 ± 4.1) U/ml) were lower than those in healthy non-CSE group ((5.1 ± 0.6), (88.4 ± 2.3) U/ml). And in COPD CSE and healthy CSE groups ((3.1 ± 0.4), (26.8 ± 6.2) U/ml) and (4.5 ± 0.4), (72.3 ± 5.1) U/ml) were respectively lower than those in COPD non-CSE and healthy non-CSE groups (all P < 0.01). The content of MDA in COPD non-CSE group was higher than that in healthy non-CSE group [(4.8 ± 0.5) vs (2.1 ± 0.4) µmol/L)]. And in COPD CSE and healthy CSE groups ((7.7 ± 0.9), (3.0 ± 0.6)µmol/L) were higher than those in COPD non-CSE and healthy non-CSE groups (all P < 0.01). At basic status, positive correlations existed between MFI and TAC, GSH-PX (r = 0.523, 0.818, P = 0.038, 0.001) while negative correlations between MFI and MDA (r = -0.501, P = 0.048) in COPD patients and after CSE treatment, the above relationships still existed (r = 0.704, 0.716, -0.522, P = 0.002, 0.002, 0.038). Cigarette smoke can reduce the phagocytosizing ability of MDM in COPD patients. And it may be related with oxidative stress.


[Evaluation of consistency of tongue and pulse signs observed by traditional Chinese medicine clinicians].
To evaluate the consistency of tongue manifestation and pulse condition observed by traditional Chinese medicine clinicians. Field investigation and direct inquiry were performed in the study. Two physicians from the same department judged tongue manifestation and pulse condition independently. The consistency among observers was assessed by means of Kappa statistics. A total of 55 patients were included in the study. There were 13 inconsistent cases (23.6%) in tongue body observation and 7 cases (12.7%) in form of the tongue observation. The observation consistency of tongue body (Kappa=0.649) and form of the tongue (Kappa=0.752) were good. There were 24 inconsistent cases (43.6%) in tongue fur observation, the consistency of which was moderate (Kappa=0.525). There were 22 inconsistent cases (40%) in pulse condition diagnosis, the diagnosis consistency of which was also moderate (Kappa=0.562). Observation and diagnosis consistency of tongue manifestation and pulse condition were moderately the same between different clinicians. By analyzing the reasons of inconsistency, it is necessary to improve the consistency in three aspects, such as the detailed-oriented criterion, the attitude of researchers and better training of researchers.


Reproducibility and intermethod reliability of a calcium food frequency questionnaire for use in Hispanic, non-Hispanic Black, and non-Hispanic White youth.
A dietary assessment instrument designed for use in a nationally representative pediatric population was required to examine associations between calcium intake and bone mineral accrual in a large, multicenter study. To determine the reproducibility and intermethod reliability of a youth calcium food frequency questionnaire (FFQ) in a multiracial/ethnic sample of children and adolescents. Reproducibility (n=69) and intermethod reliability (n=393) studies were conducted by administering repeat FFQs and three unannounced 24-hour dietary recalls to stratified random samples of individuals participating in the Bone Mineral Density in Childhood Study. Children and adolescents ages 5 to 21 years. Calcium intake estimated from the FFQ and 24-hour dietary recalls. Reproducibility was assessed by the intraclass correlation coefficient (ICC). Intermethod reliability was assessed by deattenuated Pearson correlations between the FFQ and 24-hour recalls. Attenuation factors and calibration corrected effect estimates for bone density were calculated to determine the potential influence of measurement error on associations with health outcomes. The ICC (0.61) for repeat administrations and deattenuated Pearson correlation between the FFQ and 24-hour recalls (r=0.60) for all subjects indicated reproducibility and intermethod reliability (Pearson r=0.50 to 0.74 across sex and age groups). Attenuation factors were ≤0.50 for all sex and age groups and lower for non-Hispanic blacks (λ=0.20) and Hispanics (λ=0.26) than for non-Hispanic whites (λ=0.42). The Bone Mineral Density in Childhood Study calcium FFQ appears to provide a useful tool for assessing calcium intake in children and adolescents drawn from multiracial/ethnic populations and/or spanning a wide age range. However, similar to other FFQs, attenuation factors were substantially <1, indicating the potential for appreciable measurement error bias. Calibration correction should be performed and racial/ethnic differences in performance considered when analyzing and interpreting findings based on this instrument.


Development of the optimal inoculation conditions for microcarrier cultures.
The environmental conditions under which anchorage-dependent mammalian cells are grown are not necessarily those under which a culture should be initiated. Cell attachment is a physical process, and those factors which affect forces involved in cell attachment differ from the biological factors which affect cell growth. We have conducted an extensive experimental study to define clearly the optimal environmental conditions for MRC-5 cell attachment onto microcarriers. These inoculation conditions are particularly important when the serial propagation of mammalian cells on microcarriers is considered as in a human vaccine production process. The conditions which were investigated are: initial serum content (% v/v), initial pH, inoculation level (cells/bead), agitation rate (rpm), and the concentration of microcarriers (g/L). The initial distribution of attached cells was found to have a significant affect on the overall efficiency of anchorage-dependent cell cultures, and was used to evaluate attachment efficiency. Based on the experimental results, we propose an optimized protocol for the inoculation of microcarrier cultures.


Long-term effect of parasympathetic or sympathetic denervation on intestinal epithelial cell proliferation and apoptosis.
Intestinal epithelial tissue is constantly regenerated as a means to maintain proper tissue function. Previous studies have demonstrated that denervation of the parasympathetic or sympathetic nervous system to the intestine alters this process. However, results are inconsistent between studies, showing both increases and decreases in proliferation after denervation of the parasympathetic or sympathetic. The effect appears to correlate with (1) the timing post-denervation, (2) denervation-induced changes in food intake, (3) the denervation technique used, and (4) which intestinal segment is investigated. Thus, we proposed that parasympathetic or sympathetic denervation does not have an effect on intestinal epithelial regeneration when you (1) evaluate denervation after long-term denervation, (2) control for post-surgical changes in food intake, (3) use minimally invasive surgical techniques and (4) include a segmental analysis. To test this, adult male Sprague Dawley rats underwent parasympathetic denervation via subdiaphragmatic vagotomy, sympathetic denervation via celiacomesenteric ganglionectomy, a parasympathetic denervation sham surgery, or a sympathetic denervation sham surgery. Sham surgery ad libitum-fed groups and sham surgery pair-fed groups were used to control for surgically induced changes in food intake. Three weeks post-surgery, animals were sacrificed and tissue from the duodenum, jejunum, and ileum was excised and immunohistochemically processed to visualize indicators of proliferation (bromodeoxyuridine-positive cells) and apoptosis (caspase-3-positive cells). Results showed no differences between groups in proliferation, apoptosis, or total cell number in any intestinal segment. These results suggest that parasympathetic or sympathetic denervation does not have a significant long-term effect on intestinal epithelial turnover. Thus, intestinal epithelial regeneration is able to recover after autonomic nervous system injury. Impact statement This study investigates the long-term effect of autonomic denervation on intestinal epithelial cell turnover, as measured by proliferation, apoptosis, and total cell number. Although previous research has established that autonomic denervation can alter intestinal epithelial turnover under short-term conditions, here we establish for the first time that these changes do not persist long-term when you control for surgical-induced changes in food intake and use targeted denervation procedures. These findings add to the base of knowledge on autonomic control of tissue turnover, highlight the ability of the intestinal epithelium to recover after autonomic injury and reveal possible implications of the use of ANS denervation for disease treatment in humans.


Traditional treatment of human and animal salmonelloses in Southern Benin: Knowledge of farmers and traditherapists.
This study aimed to report medicinal plants that are likely to be used in the control of salmonellosis. A cross-sectional study was conducted in Southern Benin. Semi-structured questionnaires were administered to 150 farmers and 100 traditional therapists in seven high municipalities. This step helped to collect plants that are used in the treatment of animal salmonellosis and typhoid fever in human. The results revealed a low level of use of medicinal plants among breeders who prefer antibiotics such as oxytetracycline (53.55%), tylosine + sulfadimerazine (15.30%), and alphaceryl (19.13%). However, plants such as Moringa oleifera (leaves), Carica papaya (leaves and seeds), and Vernonia amygdalina (leaves) were mostly used by some farmers. From traditional therapists, 57 plant species of 32 families were identified as typhoid fever cures; among which Leguminosae, Asteraceae, and Euphorbiaceae were predominant. Persea americana (22.72%), V. amygdalina (7.57%), and Corchorus olitorius (7.57%) were the most cited by traditherapists for the treatment of typhoid fever in human. This study provides a database for further studies on the in vitro and in vivo efficacy of Benin plant species on Salmonellaspp. These evaluations will guarantee the availability of new therapeutic solutions for populations.


Chronic cocaine administration sensitizes behavioral but not neuroendocrine responses.
Many behavioral responses to cocaine become progressively exaggerated with chronic treatment. Most studies have focused on cocaine-induced locomotor stimulation and changes in the dopamine projection systems which mediate these actions. However, it is not clear if a uniform 'sensitization' develops in all dopamine systems during chronic stimulant administration. To test this possibility the neuroendocrine actions of cocaine which are mediated, in part, by hypothalamic dopamine neurons were evaluated after chronic cocaine administration. Treatment of rats with cocaine (15 mg/kg, 2x/day) markedly enhanced the locomotor response to cocaine after 3 and 7 days of chronic administration. In contrast, neither the stimulation of adrenocorticotropic hormone (ACTH)/corticosterone (CS) secretion nor the slight inhibition of prolactin caused by acute cocaine administration changed, although a small elevation of basal corticosterone secretion was observed after 7 days. These findings suggest that the marked sensitization observed in other dopamine systems does not occur in the hypothalamic dopamine neurons thought to mediate the neuroendocrine responses to cocaine during chronic administration, despite recently described commonalities in uptake and autoreceptor functions in these dopamine cell populations. This contrast suggests a role for long loop feedback systems unique to telencephalic dopamine systems or region-specific neurochemical adaptations in cocaine sensitization.


Contactless automated manipulation of mesoscale objects using opto-fluidic actuation and visual servoing.
This work describes an automated opto-fluidic system for parallel non-contact manipulation of microcomponents. The strong dynamics of laser-driven thermocapillary flows were used to drag microcomponents at high speeds. High-speed flows allowed to manipulate micro-objects in a parallel manner only using a single laser and a mirror scanner. An automated process was implemented using visual servoing with a high-speed camera in order to achieve accurately parallel manipulation. Automated manipulation of two glass beads of 30 up to 300 μm in diameter moving in parallel at speeds in the range of mm/s was demonstrated.


In vivo effects of 1,4-dioxane on genotoxic parameters and behavioral alterations in Drosophila melanogaster.
1,4-Dioxane (DXN) is used as solvent in different consumer products including cosmetics, paints, surfactants, and waxes. In addition, DXN is released as an unwanted contaminating by-product as a result of some reactions including ethoxylation of alcohols, which occurs with in personal care products. Consequently, DXN pollution was detected in drinking water and is considered as an environmental problem. At present, the genotoxicity effects attributed to DXN are controversial. The present study using an in vivo model organism Drosophila melanogaster aimed to determine the toxic/genotoxic, mutagenic/recombinogenic, oxidative damage as evidenced by ROS production, phenotypic alterations as well as behavioral and developmental alterations that are closely related to neuronal functions. Data demonstrated that nontoxic DXN concentration (0.1, 0.25, 0.5, or 1%) induced mutagenic (1%) and recombinogenic (0.1, 0.25, or 0.5%) effects in wing spot test and genotoxicity in hemocytes using comet assay. The nontoxic concentrations of DXN (0.1, 0.25, 0.5, or 1%) significantly increased oxidative stress, climbing behavior, thermal sensivity and abnormal phenotypic alterations. Our findings show that in contrast to in vitro exposure, DXN using an in vivo model Drosophila melanogaster this compound exerts toxic and genotoxic effects. Data suggest that additional studies using other in vivo models are thus warranted.


Prevention of the death of the rat axotomized hypoglossal nerve and promotion of its regeneration by bovine brain gangliosides.
We have examined the time course of the neuronal death and regeneration of rat axotomized hypoglossal nerve with various conditions of the nerve resection, and established a useful system to measure neurotrophic activities of bioactive substances. In this system, neuronal death can be evaluated by counting surviving neurons in the nucleus of hypoglossal neuron at the brain stem, and the degree of the regeneration can be measured by counting horseradish peroxidase-positive cells at the same region after injection of horseradish peroxidase into tongue. Using this system, the effects of brain gangliosides on rat hypoglossal nerve regeneration following 5 mm transection were examined. The addition of a ganglioside mixture from bovine brain as well as the autograft strongly prevented the death of neurons and promoted the regeneration of the lesioned nerve at 10 weeks after the operation. Further analyses on the dose effects and injection sites of gangliosides were performed. Although the mechanisms of the neurotrophic effects of the gangliosides are unknown, the therapeutic application of gangliosides for neuronal degeneration is a promising approach.


Pyruvate kinase isozyme M2 and glutaminase might be promising molecular targets for the treatment of gastric cancer.
The aim of this study was to analyze the significance of glucose metabolism-related enzymes in the proliferation of gastric cancer under hypoxia. Four hypoxia-resistant gastric cancer cell lines and four parent cell lines were used. Reverse transcription-PCR was used to evaluate the mRNA expression levels of the following metabolism-related enzymes: pyruvate kinase isozyme M2 (PKM2), glutaminase (GLS), enolase 1 (ENO1), glucose-6-phosphate dehydrogenase (G6PDH), and PKM1. The effects of these enzymes on the proliferation of gastric cancer cells were examined using siRNAs, shikonin as a PKM2 inhibitor, or BPTES as a GLS inhibitor, in vitro and in vivo. Levels of both PKM2 and GLS mRNA were significantly high in all hypoxia-resistant cell lines, compared with those of their parent cells. Knockdown of PKM2 and GLS significantly decreased the proliferation of all hypoxia-resistant cells. The combination of siPKM2 and siGLS significantly decreased proliferation compared with treatment by siPKM2 or siGLS alone. The knockdown of ENO1, G6PDH, or PKM1 did not decrease the proliferation of all hypoxia-resistant cells. Combination treatment using shikonin and BPTES inhibited the proliferation of all hypoxia-resistant cancer cells more than that by either agent alone. The in vivo study indicated that the tumor size treated by the combination of shikonin and BPTES was significantly smaller than that of vehicle-treated group. These findings suggested that PKM2 and GLS might play important roles in the proliferation of hypoxic gastric cancer cells. A combination of PKM2 and GLS inhibitors could be therapeutically promising for the treatment of gastric cancer.


Rituximab induces remission in refractory HCV associated cryoglobulinaemic vasculitis.
To report the successful induction of remission with the monoclonal anti-CD20 antibody rituximab in a patient with hepatitis C virus (HCV) associated cryoglobulinaemic vasculitis and a non-Hodgkin's lymphoma (NHL) resistant to previously advocated conventional treatments. The patient was a 45 year old woman with HCV associated cryoglobulinaemic vasculitis, with purpura, arthralgia, constitutional symptoms, and a polyneuropathy. A malignant NHL was found as underlying lymphoproliferative disease. At this stage the disease was refractory to interferon alpha2b and ribavirin and to subsequent immunosuppressive treatment with cyclophosphamide. Six rituximab infusions targeting the CD20 antigen on cells of the B cell lineage induced remission of the vasculitis. Bone marrow biopsy disclosed absence of the NHL. Remission has subsequently been maintained and HCV eliminated with the new pegylated interferon alpha2b and ribavirin for nearly one year. Transition of the underlying "benign" lymphoproliferative disease to a malignant lymphoma may result in difficult to treat HCV associated cryoglobulinaemic vasculitis. Rituximab offers a new possibility for inducing remission in refractory HCV associated cryoglobulinaemic vasculitis and the lymphoproliferative disorder. After remission, HCV may subsequently be eliminated with pegylated interferon alpha2b and ribavirin.


[Diagnostic and therapeutic punctures of pancreatic cavities under control of ultrasonic investigations].
Transcutaneous puncture of pancreatic cavities under ultrasonographic control was conducted in 68 patients. The cavity contents investigation using cytological, bacteriological and biochemical methods was conducted. The method permits to diagnose the cavity, its connection with ductal system of pancreas, to select the adequate antibacterial therapy, to conduct the cavity decompression before the operation. It may be applied for symptomatic treatment conduction. There were no complications observed as a consequence of the procedure.


Stick-slip of evaporating droplets: substrate hydrophobicity and nanoparticle concentration.
The dynamics of the three-phase contact line for water and ethanol is experimentally investigated using substrates of various hydrophobicities. Different evolutions of the droplet profile (contact line, R, and contact angle, θ) are found to be dependent on the hydrophobicity of the substrate. A simple theoretical approach based on the unbalanced Young force is used to explain the depinning of the contact line on hydrophilic surfaces or the monotonic slip on hydrophobic substrates. The second part of the article involves the addition of different quantities of titanium oxide nanoparticles to water, and a comparison of the evaporative behavior of these novel fluids with the base liquid (water) on substrates varying in hydrophobicity (i.e., silicon, Cytop, and PTFE) is presented. The observed stick-slip behavior is found to be dependent on the nanoparticle concentration. The evaporation rate is closely related to the dynamics of the contact line. These findings may have an important impact when considering the evaporation of droplets on different substrates and/or those containing nanoparticles.


Anti-tumor activity of an enzymatically synthesized alpha-1,6 branched alpha-1,4-glucan, glycogen.
Oral administration of an enzymatically synthesized alpha-1,4:1,6-glycogen (ESG) at a dose of 50 mug/ml significantly prolonged the survival time of Meth A tumor-bearing mice. ESG also significantly stimulated macrophage-like cells (J774.1), leading to augmented production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha). The weight-average degree of polymerization (DPw) and the ratio of branch linkage (BL) of ESG were 149,000 and 8.1% respectively. beta-Amylase-treated ESG, however, lost J774.1-activating activity although inhibited subcutaneous growth of Meth A tumor cells admixed with it. Its DPw and BL changed to 126,000 and 20% respectively. Partially degraded amylopectin [(AP), DPw: 110,000, BL; 5.1] was also effective at stimulating J774.1, but its activity was lower than that of ESG. Other alpha-glucans [cycloamylose (CA), enzymatically synthesized amylose (ESA), highly branched cyclic dextrin (HBCD), and beta-amylase-treated HBCD], of which DPw was lower than that of ESG, showed no J774.1-activating activity and weaker anti-tumor activity.


Further observations on the behavior of staphylococci within human leukocytes.
A specific serum factor was required for rapid phagocytosis of pathogenic staphylococci by human polymorphonuclear leukocytes when the ingestion process was studied in siliconed glass systems and the concentrations of staphylococci were maintained at low levels. In contrast to certain other microbes, the resistance to phagocytosis which characterized pathogenic staphylococci was relative, and phagocytosis was readily accomplished when large populations of staphylococci were present in the test system. A factor promoting phagocytosis was present in eight of eight normal adult sera. In contrast, the sera of twenty-eight of thirty normal rabbits did not promote phagocytosis. Serum obtained from 2 rabbits maintained in the rabbit colony for several months acquired the ability to opsonize pathogenic staphylococci. The phagocytosis-promoting factor was almost completely removed by prior absorption of test sera with the homologous strain. The factor was incompletely removed by absorption with heterologous strains of pathogenic staphylococci and was not significantly reduced by absorption with coagulase-negative staphylococci or unrelated microorganisms. Present evidence suggests that the factor promoting phagocytosis is a thermostable opsonin. While the activity of heated serum could not be restored by the addition of small amounts of fresh serum or complement, the addition of large amounts of complement partially restored opsonic activity. Incubation of staphylococci in fresh serum prior to heat inactivation did not reduce subsequent phagocytosis, further suggesting the heat stability of the phagocytosis-promoting factor. Preliminary studies correlating the presence of antistaphylococcal hemagglutinins and phagocytosis-promoting factor in certain sera suggest that the two factors were not necessarily related. The phagocytosis of staphylococci in fresh human serum was inhibited by the addition of fresh or inactivated rabbit serum. Further studies on the nature of such inhibition are in progress. Once ingestion was accomplished, coagulase-positive staphylococci consistently survived in significant numbers within the cytoplasm of human granulocytes. Coagulase-negative staphylococci appeared to be destroyed within the leukocyte and could not be recultured from the cytoplasm following 3 to 4 hours of intracellular residence.


Variation in Pregnancy Options Counseling and Referrals, And Reported Proximity to Abortion Services, Among Publicly Funded Family Planning Facilities.
As frontline providers, publicly funded family planning clinics represent a critical link in the health system for women seeking information about pregnancy options, yet scant information exists on their provision of relevant services. Understanding their practices is important for gauging how well these facilities serve patients' needs. A 2012 survey of 567 publicly funded family planning facilities in 16 states gathered information on referral-making for adoption and abortion services, and perceived proximity to abortion services. Chi-square, multivariable logistic regression and multinomial logistic regression analyses were performed to assess differences among facilities in referral-making and reported proximity to abortion services. Abortion referrals were provided by a significantly smaller proportion of providers than were adoption referrals (84% vs. 97%). Health departments and community health centers were significantly less likely than comprehensive reproductive health centers to refer for abortion services and to have a list of abortion providers available (odds ratios, 0.1-0.2). Rural facilities were more likely than urban ones to report a distance of more than 100 miles to the closest first-trimester abortion provider (relative risk ratio, 11.4), second-trimester abortion provider (8.7) and medication abortion provider (8.0). Health departments were more likely than comprehensive reproductive health centers not to know the location of the closest first-trimester, second-trimester or medication abortion provider (2.5-3.5). A better understanding of disparities in provision of pregnancy options counseling and referrals at publicly funded family planning clinics is needed to ensure that women get timely care.


A retrospective comparison of blood transfusion requirements during cardiopulmonary bypass with two different small adult oxygenators.
A low haematocrit during cardiopulmonary bypass (CPB) is associated with adverse outcomes and often results in homologous blood transfusions. Oxygenators with improved venous reservoir designs aid in reducing the priming volume. Recently, we changed our small adult oxygenator model from the D905 EOS oxygenator (Dideco, Mirandola, Italy) to the Capiox FX1540 (Terumo Corporation, Tokyo, Japan). We conducted a retrospective study of 42 patents to evaluate the impact of the Capiox FX 1540 on blood transfusion requirements in small patients (body surface area (BSA) up to 1.8 m(2)). The D905 EOS group had a lower minimum intraoperative haematocrit than the FX1540 group (20 ± 3 v 22 ± 4, p = 0.029) with 73% of the patients receiving intraoperative blood transfusions compared with 30% in the FX 1540 group (p = 0.012). Patients in the D905 EOS group received one blood transfusion more during CPB than the FX 1540 patients (p = 0.002). The haematocrits at the end of CPB and in the early postoperative period were identical in both groups. The postoperative ventilation time, length of stay in the intensive care unit and postoperative chest drain bleeding were similar in both groups. In conclusion, the Capiox FX1540 was effective in reducing intraoperative packed red cell transfusions.


Cardiac troponin assay classification by both clinical and analytical performance characteristics: a study on outcome prediction.
Cardiac troponin assays have been classified according to whether they measure the 99th percentile concentration of a healthy reference population with imprecision (expressed as CV) of ≤10%, between 10% and 20%, or >20%. Assays in these categories have been deemed "guideline acceptable," "clinically usable," or "not acceptable," respectively. We compared four widely used "clinically usable" cardiac troponin I (cTnI) assays with an assay designated "not acceptable" for accuracy in predicting the clinical outcome of death. Blood was collected from 259 men and 249 women, mean (SD) age 68.8 (17.8) and 70.2 (17.8) years, respectively, admitted to the emergency department for suspected myocardial infarction. We measured cTnI by the Access, Architect, i-Stat, Stratus CS, and VIDAS assays. Deaths in this population were recorded over a 31-month period. We found VIDAS cTnI assay measurement CVs of 10% and 20% at concentrations of 0.04 and 0.02 μg/L, respectively. Comparing at the 10% CV cutoff concentration, VIDAS cTnI was less sensitive than the Access and Architect assays (P < 0.001) but more sensitive than i-Stat (P < 0.001) and Stratus CS (P < 0.001) in identifying patients with poor outcomes. At the 20% CV cutoff, the VIDAS assay was equivalent to the other assays in identifying patients with poor outcomes. For outcome prediction, the VIDAS cTnI assay was clinically equivalent or superior to other cTnI assays judged to be acceptable from a pure analytical standpoint. Thus, comparison of cardiac troponin assays should consider not only analytical performance, but also clinical performance characteristics.


[Topical diagnostic methods in primary hyperparathyroidism].
The efficiency of USI of the neck, scintigraphy of the parathyroid glands (PTG) with selen-methionine and selective catheterization of veins (SCV) of the neck and mediastinum for preoperative determination of the localization of the source of hyperproduction of the parathyroid hormone was analyzed on the basis of results of examination of 149 patients including 51 patients with primary hyperparathyroidism confirmed during the operation. It was noted that none of the methods of topical diagnostics used in the work is thought to be universal for different clinical situations. A method of their complex use is proposed which foresee USI of the neck as the first step. In case of insufficient information of the results of USI the authors propose SCV of the neck and mediastinum as a method of choice which allows the size and level of the altered PTG to become more exact and which makes further search with the help of other methods of topical diagnostics more purposeful and effective.


Development of a Low-cost, High-fidelity Skin Model for Suturing.
In a survey of students at our institution, suturing was the most desired workshop for simulation; however, cost, quality, and availability of skin pads is often prohibitive for suturing workshops. In-hospital fabrication may be utilized to manufacture noncommercial, high-fidelity, and low-cost simulation models. We describe the production, value, and face validation of our simulated skin model. Using an in-hospital fabrication laboratory, we have developed a model for skin and subcutaneous tissue. Our model uses a variety of commercially available materials to simulate the epidermis, dermis, subcutaneous fat, fascia, and muscle. A cost analysis was performed by comparing it with other commonly used commercial skin models. Expert surgeons assessed the material characteristics, durability, and overall quality of our model in comparison with other commercial models. The materials cost of our novel skin pad model was 30.9% of the mean cost of five different commonly used foam and silicone-based commercial skin models. This low-cost model is more durable than the commercial models, does not require skin pad holders, and is of higher fidelity than the commercial products. In addition to skin closure, our model may be used to simulate fascial closure or fasciotomy. Model creation using in-hospital workspaces is an effective strategy to decrease cost while improving quality of surgical simulation. Our methods for creation of an inexpensive and high-fidelity skin pad may be purposed for several soft tissue models.


[Supportive therapy in oncology].
The current trend towards a more intensive cancer treatment is possible thanks to the availability of a really important and effective supportive care. It is our opinion that it would be essential for the junior staff in oncology, for the practitioners, but also for the knowledge of anyone contributing in different ways to give the cancer treatment, to have reference points to give also the best supportive care. With this aim we thought to start a study, in Italy, to investigate, first, which is the supportive care used in the most common acute toxicities during or immediately after cancer therapy. We decided to begin with a survey addressed to hematologists, medical oncologists, radiotherapists; 105 centers were contacted. In order to have a high number of people able to answer to different clinical questions we decided to use Internet to communicate with participating centers without moving people. The final goal of the project is to formulate guidelines in supportive care, but also to promote the use of Internet as much as possible in the medical world with the aim to make easier every kind of communication and exchange of information.


N-acylation of glucosamine modulates chondrocyte growth, proteoglycan synthesis, and gene expression.
To examine the effects of glucosamine (GlcN) and some N-acylated (GlcNAcyl) derivatives on the proliferation and proteoglycan (PG) synthesis of bovine articular chondrocyte (BAC); and to expand these results to human articular chondrocytes (HAC) and study the modulation of gene regulation by these compounds. The compounds tested were: glucose (Glc), GlcN.HCl, N-acetyl GlcN (GlcNAc), and N-butyryl GlcN, (GlcNBu). GlcNBu was synthesized from GlcN and butyric anhydride. For the chondrocyte cultures, both anchorage-dependent (AD) and an anchorage-independent (AI) system (alginate beads) were evaluated. Following the various additions, BAC were assessed for total cell number, DNA, or total PG synthesis at different times. Utilizing similar conditions, human cDNA microarrays were performed for the HAC after harvesting total RNA. For AD cultures, the addition of GlcN.HCl (0.1-5.0 mM) to BAC or HAC cultures inhibited cell proliferation and total PG synthesis in a dose-dependent manner. For AI cultures, the inhibitory effects of GlcN.HCl on cell proliferation were less prominent, and PG synthesis increased slightly more for the GlcNAcyl than the GlcN additions. In the AD system, the addition of GlcNAc did not result in the inhibitory effect of GlcN.HCl, while GlcNBu addition resulted in an increase in BAC proliferation and PG synthesis that could not be explained by the Bu moiety alone. For the HAC, additions of 0.1 mM GlcNBu resulted in upregulation of a large number of genes, with only a few downregulated, while GlcN addition resulted in no upregulation and one downregulated gene, for preset stringency criteria. Addition of GlcNBu to BAC or HAC to AD cultures generally stimulated cell proliferation and PG synthesis, while addition of GlcN resulted in inhibition of these indicators. The inhibitory effects of the GlcN molecule appear to be related to the unsubstituted amino group. Additions of GlcNBu, but not GlcN, to HAC resulted in upregulation in the expression of a large number of genes.


An evaluation of the applicability of crossed immunoelectrophoresis in seroepidemiological studies of hydatid disease in livestock.
Hydatidosis is both an economic and public health problem all over the world. Although various tests have been used on serodiagnosis of the disease in laboratory infected sheep, there is a problem in detecting antibody to the parasite in sheep. The antibody response of people infected with E. granulosus differs from the antibody response of livestock. Crossed immunoelectrophoresis was used to search for antibodies in 44 goats known to have had the infection. Crossed immunoelectrophoresis was able to detect two antibodies produced by a goat naturally infected with hydatid disease. Three of 44 known cases were detected by the test method. None of the naturally infected animals' sera exhibited a pattern of arcs similar to the reference pattern. The test's sensitivity was poor.


Role and regulation of class-C flavodiiron proteins in photosynthetic organisms.
The regulation of photosynthesis is crucial to efficiently support the assimilation of carbon dioxide and to prevent photodamage. One key regulatory mechanism is the pseudo-cyclic electron flow (PCEF) mediated by class-C flavodiiron proteins (FLVs). These enzymes use electrons coming from Photosystem I (PSI) to reduce oxygen to water, preventing over-reduction in the acceptor side of PSI. FLVs are widely distributed among organisms performing oxygenic photosynthesis and they have been shown to be fundamental in many different conditions such as fluctuating light, sulfur deprivation and plant submersion. Moreover, since FLVs reduce oxygen they can help controlling the redox status of the cell and maintaining the microoxic environment essential for processes such as nitrogen fixation in cyanobacteria. Despite these important roles identified in various species, the genes encoding for FLV proteins have been lost in angiosperms where their activity could have been at least partially compensated by a more efficient cyclic electron flow (CEF). The present work reviews the information emerged on FLV function, analyzing recent structural data that suggest FLV could be regulated through a conformational change.


[Dynamics of 134 + 137Cs accumulation in insects inhabiting the 30-kilometer zone of Chernobyl Nuclear Power Station].
Accumulation of the specific activity of 134 + 137Cs in insects was investigated in the most typical biogeocenoses within the 30-km zone of the Chernobyl NPP. The studied biogeocenoses had different rates of the exposure doses. It was shown that the specific activity of 134 + 137Cs in the insects inhabiting forest biotops was of the same order that in the crown, whereas in the insects inhabiting open biotops the specific activity was higher than in plants. Two periods of the increased 134 + 137Cs content in insects were found: May and September. Along with seasonal activity variations, a tendency to decreasing and stabilization of 134 + 137Cs content was observed during the period of the study.


Treatment of sexual precocity by removal of a luteinizing hormone-releasing hormone secreting hamartoma.
A 1-year-old infant was initially seen with precocious puberty that progressed rapidly and was associated with episodic gonadotropin release. A computed tomographic metrizamide cisternogram showed a pedunculated mass below the tuber cinereum; the mass was resected. His pubertal development regressed, his accelerated growth ceased, and his hormone levels returned to the normal prepubertal range. Immunocytochemical studies of the tissue demonstrated luteinizing hormone-releasing hormone (LHRH) granules in the perikaryon of neurons and axons in the hamartoma and axons connecting the hamartoma to the tuber cinereum. These data suggest that such lesions cause pubertal development by stimulating gonadotropin secretion via episodic release of LHRH. If such lesions are pedunculated, operative resection may be the treatment of choice.


Pharmacodynamic interaction between ezetimibe and rosuvastatin.
Ezetimibe is a lipid-lowering drug indicated for the treatment of hypercholesterolemia as co-administration with HMG-CoA reductase inhibitors (statins) or as monotherapy. The primary objectives of this study were to evaluate the pharmacodynamic effects and safety of the co-administration of ezetimibe and the new statin rosuvastatin. A secondary objective was to examine the potential for a pharmacokinetic interaction between ezetimibe and rosuvastatin. This was a randomized, evaluator (single)-blind, placebo-controlled, parallel-group study in healthy hypercholesterolemic subjects (untreated low-density lipoprotein cholesterol [LDL-C] > or = 130 mg/dL [3.37 mmol/L]). After the outpatient screening and NCEP Step I diet stabilization periods, 40 subjects were randomized to one of the 4 following treatments: rosuvastatin 10 mg plus ezetimibe 10 mg (n = 12); rosuvastatin 10 mg plus placebo (matching ezetimibe 10 mg) (n = 12); ezetimibe 10 mg plus placebo (matching ezetimibe 10 mg) (n = 8); or placebo (2 tablets, matching ezetimibe 10 mg) (n = 8). All study treatments were administered once daily in the morning for 14 days as part of a 16-day inpatient confinement period. Fasting serum lipids were assessed pre-dose on days 1 (baseline), 7, and 14 by direct quantitative assay methods. Safety was evaluated by monitoring laboratory tests and recording adverse events. Blood samples were collected for ezetimibe and rosuvastatin pharmacokinetic evaluation prior to the first and last dose and at frequent intervals after the last dose (day 14) of study treatment. Plasma ezetimibe, total ezetimibe (ezetimibe plus ezetimibe-glucuronide) and rosuvastatin concentrations were determined by validated liquid chromatography with tandem mass spectrometric detection (LC-MS/MS) assay methods. All active treatments caused statistically significant (p < or = 0.02) decreases in LDL-C concentration versus placebo from baseline to day 14. The co-administration of ezetimibe and rosuvastatin caused a significantly (p < 0.01) greater reduction in LDL-C and total cholesterol than either drug alone. In this 2-week inpatient study with restricted physical activity there was no apparent effect of any treatment on high-density lipoprotein cholesterol (HDL-C) or triglycerides. The co-administration of ezetimibe and rosuvastatin caused a significantly (p < 0.01) greater percentage reduction in mean LDL-C (-61.4%) than rosuvastatin alone (-44.9%), with a mean incremental reduction of -16.4% (95%CI -26.3 to -6.53). Reported side effects were generally mild, nonspecific, and similar among treatment groups. There were no significant increases or changes in clinical laboratory tests, particularly those assessing muscle and liver function. There was no significant pharmacokinetic drug interaction between ezetimibe and rosuvastatin. Co-administration of ezetimibe 10 mg with rosuvastatin 10 mg daily caused a significant incremental reduction in LDL-C compared with rosuvastatin alone. Moreover, co-administering ezetimibe and rosuvastatin was well tolerated in patients with hypercholesterolemia.


Suppressing wall turbulence by means of a transverse traveling wave
Direct numerical simulations of wall-bounded flow reveal that turbulence production can be suppressed by a transverse traveling wave. Flow visualizations show that the near-wall streaks are eliminated, in contrast to other turbulence-control techniques, leading to a large shear stress reduction. The traveling wave can be induced by a spanwise force that is confined within the viscous sublayer; it has its maximum at the wall and decays exponentially away from it. We demonstrate the application of this approach in salt water, using arrays of electromagnetic tiles that produce the required traveling wave excitation at a high efficiency.


The Neurosurgical Atlas: advancing neurosurgical education in the digital age.
The advent of the internet and the popularity of e-learning resources has promoted a shift in medical and surgical education today. The Neurosurgical Atlas has sought to capitalize on this shift by providing easily accessible video and online education to its users on an international scale. The rising popularity of social media has provided new avenues for expanding that global reach, and the Atlas has sought to do just that. In this study, the authors analyzed user demographics and web traffic patterns to quantify the international reach of the Atlas and examined the potential impact of social media platforms on the expansion of that reach. Twitter, Facebook, and Instagram metrics were extracted using each respective service's analytics tool from the date of their creation through October 2019. Google Analytics was used to extract website traffic data from September 2018 to September 2019 and app data from January 2019 to October 2019. The metrics extracted included the number of platform users/followers, user demographic information, percentage of new versus returning visitors, and a number of platform-specific values. Since the authors' previous publication in 2017, annual website viewership has more than doubled to greater than 500,000 viewing sessions in the past year alone; international users accounted for more than 60% of the visits. The Atlas Twitter account, established in August 2012, has more than 12,000 followers, primarily hailing from the United States, the United Kingdom, Canada, and Saudi Arabia. The Atlas Facebook account, established in 2013, has just over 13,000 followers, primarily from India, Egypt, and Mexico. The Atlas Instagram account (established most recently, in December 2018) has more than 16,000 followers and the highest percentage (31%) of younger users (aged 18-24 years). The Atlas app was officially launched in May 2019, largely via promotion on the Atlas social media platforms, and has since recorded more than 60,000 viewing sessions, 80% of which were from users outside the United States. The Neurosurgical Atlas has attempted to leverage the many e-learning resources at its disposal to assist in spreading neurosurgical best practice on an international scale in a novel and comprehensive way. By incorporating multiple social media platforms into its repertoire, the Atlas is able to ensure awareness of and access to these resources regardless of the user's location or platform of preference. In so doing, the Atlas represents a novel way of advancing access to neurosurgical educational resources in the digital age.


Selective Viral and Rickettsial Serum Antibody Absorption by a Chromatographic Column.
Serum antibodies behave as cations at neutral pH and thus have low affinity for cellulose anion-exchange columns. Antigens of small size derived from adenovirus, influenza virus, and typhus rickettsiae, however, readily adsorbed to such columns. These adsorbed antigens specifically removed antibodies from antisera. This simple method permits antibody absorption by antigens ordinarily sedimented with difficulty.


Golf-related low back pain: a review of causative factors and prevention strategies.
Golf is a popular sport with both perceived and real health benefits. However, certain injury risks are also prevalent, particularly to the lower back. Epidemiological studies have shown that lower back pain (LBP) from golf account for between 18% and 54% of all documented ailments, leading many researchers to regard the condition as the most common golf injury. The purpose of this review was to examine the scientific literature to ascertain the risk factors associated with the development of LBP from playing golf and suggest methods to modify or limit these factors. Results of the review indicate that the high frequency of LBP appears multi-factorial although the asymmetrical and forceful nature of the swing along with excessive play and practice, particularly amongst elite players, appear to be common factors. Other factors include swing flaws leading to excessive side-bend and over-rotation of the spine, abnormal muscle recruitment, poor trunk endurance, restricted lead hip internal rotation and the use of unnecessarily stressful club transportation methods. Methods to help control or eliminate excessive stress on the lower back would include reducing the amount spent playing or practicing, seeking professional assistance to assess and adjust swing mechanics, improve trunk and hip flexibility, increase the strength and endurance of the trunk musculature, consider different footwear options and avoid carrying the golf bag. Adopting some or all of these recommendations should allow players to continue to enjoy the sport of golf well into their senior years.


Blood pressure lowering efficacy of renin inhibitors for primary hypertension.
Hypertension is a chronic condition associated with an increased risk of mortality and morbidity. Renin is the enzyme responsible for converting angiotensinogen to angiotensin I, which is then converted to angiotensin II. Renin inhibitors are a new class of drugs that decrease blood pressure (BP) by preventing the formation of both angiotensin I and angiotensin II. To quantify the dose-related BP lowering efficacy of renin inhibitors compared to placebo in the treatment of primary hypertension.To determine the change in BP variability, pulse pressure, and heart rate and to evaluate adverse events (mortality, non-fatal serious adverse events, total adverse events, withdrawal due to adverse effects and specific adverse events such as dry cough, diarrhoea and angioedema). The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to February 2017: the Cochrane Hypertension Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 2), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. There was no restriction by language or publication status. We also searched the European Medicines Agency (EMA) for clinical study reports, the Novartis Clinical Study Results Database, bibliographic citations from retrieved references, and contacted authors of relevant papers regarding further published and unpublished work. We included randomized, double-blinded, placebo-controlled studies evaluating BP lowering efficacy of fixed-dose monotherapy with renin inhibitor compared with placebo for a minimum duration of three to 12 weeks in adult patients with primary hypertension. This systematic review is a comprehensive update which includes four additional studies and extensive detail from nine clinical study reports (CSRs) of previously included studies obtained from EMA. The remaining three CSRs are not available.Two review authors independently assessed study eligibility and extracted data. In all cases where there was a difference between the CSR and the published report, data from the CSR was used. Dichotomous outcomes were reported as risk ratio (RR) with 95% confidence intervals (CIs) and continuous outcomes as mean difference (MD) with 95% CIs. 12 studies (mean duration of eight weeks) in 7439 mostly Caucasian patients (mean age 54 years) with mild-to-moderate uncomplicated hypertension were eligible for inclusion in the review. Aliskiren was the only renin inhibitor evaluated. All included studies were assessed to have high likelihood of attrition, reporting and funding bias.Aliskiren has a dose-related systolic/diastolic blood pressure (SBP/DBP) lowering effect as compared with placebo MD with 95% CI: aliskiren 75 mg (MD -2.97, 95% CI -4.76 to -1.18)/(MD -2.05, 95% CI -3.13 to -0.96) mm Hg (moderate-quality evidence), aliskiren 150 mg (MD -5.95, 95% CI -6.85 to -5.06)/ (MD -3.16, 95% CI -3.74 to -2.58) mm Hg (moderate-quality evidence), aliskiren 300 mg (MD -7.88, 95% CI -8.94 to -6.82)/ (MD -4.49, 95% CI -5.17 to -3.82) mm Hg (moderate-quality evidence), aliskiren 600 mg (MD -11.35, 95% CI -14.43 to -8.27)/ (MD -5.86, 95% CI -7.73 to -3.99) mm Hg (low-quality evidence). There was a dose-dependent decrease in blood pressure for aliskiren 75 mg, 150 mg and 300 mg. The blood pressure lowering effect of aliskiren 600 mg was not different from 300 mg (MD -0.61, 95% CI -2.78 to 1.56)/(MD -0.68, 95% CI -2.03 to 0.67). Aliskiren had no effect on blood pressure variability. Due to very limited information available regarding change in heart rate and pulse pressure, it was not possible to meta-analyze these outcomes.Mortality and non-fatal serious adverse events were not increased. This review found that in studies of eight week duration aliskiren may not increase withdrawal due to adverse events (low-quality evidence). Diarrhoea was increased in a dose-dependent manner (RR 7.00, 95% CI 2.48 to 19.72) with aliskiren 600 mg (low-quality evidence). The most frequent adverse events reported were headache, nasopharyngitis, diarrhoea, dizziness and fatigue. Compared to placebo, aliskiren lowered BP and this effect is dose-dependent. This magnitude of BP lowering effect is similar to that for angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). There is no difference in mortality, nonfatal serious adverse events or withdrawal due to adverse effects with short term aliskiren monotherapy. Diarrhoea was considerably increased with aliskiren 600 mg.


Tactile stimulus predictability modulates activity in a tactile-motor cortical network.
Manipulating objects in the hand requires the continuous transformation of sensory input into appropriate motor behaviour. Using a novel vibrotactile device combined with fMRI, the cortical network associated with tactile sensorimotor transformations was investigated. Continuous tactile stimuli were delivered in a random or predictable pattern to the second digit on the right hand of all subjects. To better distinguish sensory and motor processes, subjects were instructed to make proportionate motor gripping responses with their left hand. A consistent cortical network of activation was revealed that included the supplementary motor, dorsal and ventral premotor, posterior parietal, primary and secondary somatosensory and primary motor cortex. Tracking the unpredictable versus predictable tactile stimulus led to greater delays in motor responses and to increased performance errors. Cortical effects due to stimulus predictability were observed in several components of the network, though it was most evident as increased cortical activation in frontal motor regions during tracking of unpredictable tactile stimuli. In contrast to the proposed hypotheses, primary and secondary somatosensory cortices contralateral to tactile input did not reveal enhanced responses during unpredictable tracking. Facilitation during unpredictable tracking was also observed in primary somatosensory cortex contralateral to motor responses, the receptive site for movement-related afference. The present study provides a novel and controlled approach to investigate the loci associated with tactile-motor processing and to measure the task-specific effect of stimulus predictability on network components.


Fatigue Among Adults With Type 1 Diabetes Mellitus and Implications for Self-Management: An Integrative Review.
Purpose The aim of this review was to integrate empirical and theoretical literature on fatigue among adults with type 1 diabetes mellitus (T1DM). A methodological review using an integrative approach was used. Databases MEDLINE via Pubmed, CINAHL, PsycINFO, and Science Direct were searched for peer-reviewed articles published in English from 2007-2017, using the following search terms and Boolean operators: "Type 1 Diabetes" and "Fatigue." Of 199 articles initially retrieved, 14 were chosen for inclusion. These articles included 13 quantitative (7 cross-sectional, 2 cohort, 2 secondary data analyses, 2 experimental) and 1 qualitative phenomenology. Fatigue was identified as one of the most troublesome symptoms reported in persons with T1DM. Four main themes emerged: fatigue in T1DM is multidimensional and related to psychological, physiological, situational, and sociodemographic factors. Conclusions Fatigue is considered a classic symptom of hyperglycemia; however, there were minimal data to support the theory that fatigue is related to hyperglycemia or hypoglycemia. Studies on fatigue among persons with T1DM are limited to small samples and cross-sectional designs with few randomized controlled trials addressing fatigue and diabetes-related symptoms. Evidence is conflicting regarding the onset of fatigue among persons with T1DM and the relationship between fatigue and diabetes duration. The prevalence of fatigue is likely influenced by disease physiology, psychological stress, and lifestyle factors, but more research is needed to confirm these relationships as causal inference is unclear.


Antigen-specific cells in mouse bone marrow. II. Fluctuation of the number and potential of immunocyte precursors after immunization.
Quantitative and qualitative changes of mouse bone marrow cells were studied by limiting dilution assays 2-3.5 months after immunization of donors with sheep erythrocytes or unrelated antigens (Salmonella typhimurium, horse and chicken erythrocytes). Irradiated (C3H x C57BL/10)F(1) mice were reconstituted with an excess of nonprimed thymocytes and small graded numbers of primed bone marrow cells. Direct and indirect plaque-forming cells (PFC) were induced by secondary stimulation with SRBC and enumerated on the 9th day after cell transplantation. Marrow precursors of PFC (P-PFC) cooperated with thymocytes in the production of direct and indirect PFC after SRBC priming. The limiting dilution plots, which were not compatible with predictions of the Poisson model before immunization, changed and conformed to this model afterwards, as if the population of P-PFC had become functionally more homogeneous. The concentration of marrow P-PFC increased up to the 3rd month after priming, and decreased during the 4th, varying over two logarithms of nucleated marrow cells. The fluctuation was simultaneous and of the same order of magnitude for precursors of direct and indirect PFC, which were class restricted. A third effect of immunization was detected at 3.5 months: individual precursor units generated 3-4 times more direct and indirect PFC than at earlier intervals. Qualitative and quantitative changes of marrow P-PFC participating in anti-sheep responses were specific, since antigens unrelated to SRBC failed to induce them. The data suggested that marrow-derived cells were the major carriers of immunologic memory, but that they functioned in cooperation with thymus-derived inducer cells during secondary anti-sheep responses.


Ex situ population management in the absence of pedigree information.
For captive breeding to play a significant role in conservation, ex situ populations must be scientifically managed to meet objective goals for retaining representative genetic variation. Imperfect genealogical information requires fundamental assumptions to be made that may bias downstream measures of genetic importance, upon which management decisions are based. The impacts of such assumptions are most pronounced within breeding programmes characterized by a high proportion of individuals of unknown ancestry, as exemplified by the large captive population of the St Vincent parrot (Amazona guildingii). The degree to which microsatellite-based estimates of relatedness may improve upon the assumptions of conventional pedigree-based management was investigated using genotypic data collected at eight microsatellite loci and two marker-based relatedness estimators. The measure, rxyLR, was found to explain the highest amount of variation in true relatedness. Integration of pairwise estimates of founder relatedness with studbook data transformed current understanding of the relatedness structure of the A. guildingii population from two subgroups characterized by a high and low degree of relatedness, respectively, to a situation where all 72 individuals are prioritized for breeding according to their estimated mean kinships. Furthermore, the discovery of opposing, directional bias exhibited by rxyLR and rxyQG in assigning dyads to a given relationship category suggests that an approach that utilizes a combination of pairwise relatedness estimators may provide the most genetic information for balancing the dual considerations of maximizing gene diversity and minimizing inbreeding in developing breeding recommendations.


Bacterial dacryoadenitis: clinical features, microbiology, and management of 45 cases, with a recent uptick in incidence.
To review the clinical features, microbiology, management, and incidence of bacterial dacryoadenitis at our institution. This was a case series examining patients with bacterial dacryoadenitis from 2004 to 2020. Charts were reviewed for demographics, comorbidities, presenting symptoms and signs, radiology, microbiology, and management. Main outcomes included need for surgical intervention or inpatient admission. Forty-five patients with bacterial dacryoadenitis had a mean age of 46.1 years. Presenting symptoms included eyelid edema (100%), extraocular motility restriction (53.3%), and purulent discharge (75.5%). Based on computed tomography or magnetic resonance imaging, 9 (20.5%) patients presented with definite abscess and 15 (34%) presented with a phlegmon or early abscess. Eleven patients (24.4%) required surgical drainage. Twenty patients (44.4%) required admission, for an average stay of 4 days (range 2-8 days). Common organisms included Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus. Presence of an early abscess or phlegmon correlated with need for drainage (p < 0.01). Extraocular motility restriction correlated with need for drainage (p = 0.02) and admission (p = 0.05). The incidence of bacterial dacryoadenitis at our institution increased as a percentage of confirmed dacryoadenitis cases; from 2004 to 2010 the incidence was 0 to 9.1% per year, while from 2010 to 2019 the incidence ranged from 7.7 to 36.2%. In 2019, our institution had 17 cases (incidence 36.2%) of bacterial dacryoadenitis. Bacterial dacryoadenitis is a major cause of dacryoadenitis, and its incidence may be increasing. It can resolve with minimal complications if managed appropriately, although some patients may require surgical drainage or admission for intravenous antibiotics.


Subcellular localization of the Streptococcus mutans P1 protein C terminus.
To determine the subcellular location of the Streptococcus mutans P1 protein C-terminal anchor, cell envelope fractionation experiments were conducted in combination with Western immunoblotting, using monoclonal antibody MAb 6-8C specific for an epitope that maps near the C terminus of P1 protein and also a polyclonal antibody preparation directed against the P1 C-terminal 144 amino acids (P1COOH). P1 protein was detected in cell walls but not the membrane purified from S. mutans cells by the monoclonal antibody. In contrast, P1 protein was not detected in the same cell wall preparation using the anti-P1COOH polyclonal antibody. However, proteins released from the cell walls by treatment with mutanolysin contained antigen that was recognized by the anti-P1COOH antibody, suggesting that the epitopes recognized by the antibody were masked by peptidoglycan in the cell wall preparations. When cell walls were treated with boiling trichloroacetic acid to solubilize cell-wall-associated carbohydrate, P1 antigen could not be detected in either the solubilized carbohydrate, or in the remaining peptidoglycan, regardless of whether polyclonal or monoclonal antibody was used. However, when the peptidoglycan was treated with mutanolysin, P1 antigen could be detected in the mutanolysin solubilized fraction by MAb 6-8C. Collectively, these data suggest that the C-terminal 144 amino acids of the P1 protein are embedded within the cell wall, and associated exclusively with the peptidoglycan. Furthermore, the ability of the anti-P1COOH antibody to recognize P1 antigen only after mutanolysin treatment of cell walls suggests these C-terminal 144 amino acids are tightly intercalated within the peptidoglycan strands.


The Rise of Concussions in the Adolescent Population.
Concussion injuries have been highlighted to the American public through media and research. While recent studies have shown increased traumatic brain injuries (TBIs) diagnosed in emergency departments across the United States, no studies have evaluated trends in concussion diagnoses across the general US population in various age groups. To evaluate the current incidence and trends in concussions diagnosed across varying age groups and health care settings in a large cross-sectional population. Descriptive epidemiological study. Administrative health records of 8,828,248 members of a large private-payer insurance group in the United States were queried. Patients diagnosed with concussion from years 2007 through 2014 were stratified by year of diagnosis, age group, sex, classification of concussion, and health care setting of diagnosis (eg, emergency department vs physician's office). Chi-square testing was used for statistical analysis. From a cohort of 8,828,248 patients, 43,884 patients were diagnosed with a concussion. Of these patients, 55% were male and over 32% were in the adolescent age group (10-19 years old). The highest incidence of concussion was seen in patients aged 15 to 19 years (16.5/1000 patients), followed by those aged 10 to 14 years (10.5/1000 patients), 20 to 24 years (5.2/1000 patients), and 5 to 9 years (3.5/1000 patients). Overall, there was a 60% increase in concussion incidence from 2007 to 2014. The largest increases were in the 10- to 14-year (143%) and 15- to 19-year (87%) age groups. Based on International Classification of Disease-9th Revision classification, 29% of concussions were associated with some form of loss of consciousness. Finally, 56% of concussions were diagnosed in the emergency department and 29% in a physician's office, with the remainder in urgent care clinics or inpatient settings. The incidence of concussion diagnosed in the general US population is increasing, driven largely by a substantial rise in the adolescent age group. The youth population should be prioritized for ongoing work in concussion education, diagnosis, treatment, and prevention. The rise of concussions in the adolescent age group across the general population is concerning, and clinical efforts to prevent these injuries are needed.


[Metabolism of enkephalins in various functional and pathological states of the body].
The peculiarities of metabolism of enkephalins at different functional conditions of the organism, different pathology and at the influence of some extreme factors are considered. Some special attention is given to the problem of interrelation and interdependence of enkephalins with proteolytic enzymes, participating in their synthesis and degradation. It is concluded that the biological property of neuropeptides as well as their participation in different physiological and pathological conditions of the organism very much depend on the peculiarities of functioning of enzyme systems of metabolism of neuropeptides.


Begin with the End in Mind: A three-part workshop series to facilitate end-of-life discussions with members of the community.
Death is among the most avoided topics of conversation. Although end-of-life planning may greatly benefit individuals and their survivors, research and practice indicate that family, friends, and even health care providers resist discussing end-of-life plans. Consequences of not planning ahead have created a public health issue. This article describes a community-level intervention that facilitates those necessary conversations among elders who have at least begun to talk with others about their wishes. A free, three-part educational workshop series on end-of-life planning titled "Begin with the End in Mind" was developed at a midwestern university. A survey was distributed to all attendees to learn about their beliefs regarding end-of-life planning. Inductive content analysis was used to understand participants' thoughts about discussing end-of-life planning. Findings from 33 participants suggest a concern about making plans and ensuring others would follow their wishes. In conclusion, this article offers a roadmap for gerontologists and others to use in engaging the community to think about and act on end-of-life public health issues.


Establishing the validity of surface topography for assessment of scoliosis: a prospective study.
Descriptive survey. Compare radiographic parameters measured using surface topography (ST) with those obtained radiographically to determine the validity of ST for scoliotic assessment. While anterior-posterior radiography is the gold standard for diagnosing scoliosis, repeated radiographic use is associated with increased carcinogenicity. Studies have thus focused on radiation-free systems, including ST, to calculate the scoliotic angle. Seventeen patients ages 25-76 were included. Each patient received one AP radiograph and three repeated ST measurements over two months. Values were analyzed by two raters to determine comparability between ST and radiographic measurements. Interobserver reliability (ICC) was calculated and statistical significance was determined by the p-value of a paired two-tailed t-test. ICC showed excellent reliability (> 0.90). There was no significant difference (p > 0.40) in apical vertebral deviation/translation between conventional radiography (0.9 ± 0.8) and ST (1.2 ± 1.0). There was no significant difference (p > 0.30) in sagittal balance radiographic (4.0 ± 3.1) and ST (4.4 ± 3.3), and coronal balance radiographic (1.4 ± 1.3) and ST (1.1 ± 1.1) measurements. Significant difference (p < .001) was found between lumbar lordosis radiographic (52.6 ± 18.4) and ST (37.9 ± 16.6), kyphotic angle radiographic (35.1 ± 16.0) and ST (50.0 ± 11.9), and scoliotic angle radiographic (11.3 ± 12.4) and ST (17.7 ± 10.2) measurements. No significant difference was observed between various ST and radiographic measurements, including apical vertebral deviation, sagittal balance, and coronal balance. While a larger prospective study is needed to further assess the validity of ST, these initial measurements suggest the possibility of an effective and radiation-free adjunctive method of assessing balance in the coronal plane.


Evolution of Class I cytokine receptors.
The Class I cytokine receptors have a wide range of actions, including a major role in the development and function of immune and blood cells. However, the evolution of the genes encoding them remains poorly understood. To address this we have used bioinformatics to analyze the Class I receptor repertoire in sea squirt (Ciona intestinalis) and zebrafish (Danio rerio). Only two Class I receptors were identified in sea squirt, one with homology to the archetypal GP130 receptor, and the other with high conservation with the divergent orphan receptor CLF-3. In contrast, 36 Class I cytokine receptors were present in zebrafish, including representative members for each of the five structural groups found in mammals. This allowed the identification of 27 core receptors belonging to the last common ancestor of teleosts and mammals. This study suggests that the majority of diversification of this receptor family occurred after the divergence of urochordates and vertebrates approximately 794 million years ago (MYA), but before the divergence of ray-finned from lobe-finned fishes around 476 MYA. Since then, only relatively limited lineage-specific diversification within the different Class I receptor structural groups has occurred.


Differential expression of HLA-DR antigens in subsets of human CFU-GM.
Expression of HLA-DR surface antigens by granulocyte/monocyte colony-forming cells (CFU-GM) may be important in the regulation of proliferation of these cells. Using immunological techniques to enrich for progenitor cells, we investigated the expression of HLA-DR in subsets of CFU-GM. "Early" (day 14) CFU-GM express higher levels of HLA-DR than do "late" (day 7) CFU-GM. Among late CFU-GM, cells destined to form monocyte (alpha-naphthyl acetate esterase-positive) colonies express higher levels of HLA-DR than do CFU-GM destined to form granulocyte (chloroacetate esterase-positive) colonies. Because high-level expression of DR antigen was a marker for monocyte differentiation, we examined several lymphokines for their effects on both DR expression and in vitro commitment to monocyte differentiation by myeloid precursor cells. DR antigen density could be increased by more than twofold over 48 hours upon exposure to gamma-interferon (gamma-IFN), whereas colony-stimulating factors had no effect. This was associated with a dose-dependent inhibition of total CFU-GM number, and a relative, but not absolute, increase in the ratio of monocyte colonies to granulocyte colonies. Similarly, in day 7 suspension cultures of purified myeloid precursor cells, gamma-IFN inhibited cell proliferation and increased the ratio of monocytes to granulocytes. Thus, despite the induction of high levels of HLA-DR antigen on precursor cells (a marker of monocyte commitment), the dominant in vitro effect of gamma-IFN was inhibition of granulocyte differentiation.