Investigation of the Diagnostic Value of sFLC and Other Indicators in the Detection of M Protein in LCMM.
The aim was to explore the diagnostic value of serum free light chain (sFLC) and other laboratory indicators for the patients with light chain multiple myeloma (LCMM). We performed a retrospective study including 82 LCMM cases and 43 healthy subjects as the observation and control groups, respectively. The observation group was further divided into two subgroups: κ- and λ-type LCMM. Sixteen quantitative indicators were collected and the difference among groups was compared. We also evaluated the positive detection rate (PDR) of four qualitative indicators for M protein detection. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of sixteen indicators. Fourteen indicators showed statistical differences between the control group and κ- or λ-type LCMM subgroup. The κ and λ sFLC ratio (rFLC) and the difference between κ and λ FLC (dFLC) showed differences among the three groups. Among the four qualitative indicators of M protein detection, rFLC showed the highest PDR for both κ- and λ-type LCMM. Among the three combinations with rFLC or uIFE did not show statistical differences. ROC curve analysis indicated a relatively high diagnostic value of dFLC for both κ- and λ-type LCMM. We should be vigilant about the missed diagnosis by observing the changes of MM-related indicators, particularly dFLC and the six other indicators with high diagnostic value. rFLC can improve the diagnostic ability of LCMM.


High-resolution X-ray topographic images of dislocations in a silicon crystal recorded using an X-ray zooming tube.
A Be-window-type X-ray zooming tube is an X-ray digital imaging system whose magnification factor of X-ray images can be easily varied from 10 to 200, and whose spatial resolution is less than 0.5 micro m. This zooming tube was used as an imaging detector in double-crystal X-ray topography to obtain high-resolution images of dislocations in a silicon crystal. X-ray interference images of about 5 micro m were observed even though optimal performance of the X-ray zooming tube could not be achieved. The results indicate that the X-ray zooming tube might make a good detector for X-ray topography with minor improvements in its stage structure.


Antarctic bacterial haemoglobin and its role in the protection against nitrogen reactive species.
In a cold and oxygen-rich environment such as Antarctica, mechanisms for the defence against reactive oxygen and nitrogen species are needed and represent important components in the evolutionary adaptations. In the Antarctic bacterium Pseudoalteromonas haloplanktis TAC125, the presence of multiple genes encoding 2/2 haemoglobins and a flavohaemoglobin strongly suggests that these proteins fulfil important physiological roles, perhaps associated to the peculiar features of the Antarctic habitat. In this work, the putative role of Ph-2/2HbO, encoded by the PSHAa0030 gene, was investigated by in vivo and in vitro experiments in order to highlight its involvement in NO detoxification mechanisms. The PSHAa0030 gene was cloned and then over-expressed in a flavohaemoglobin-deficient mutant of Escherichia coli, unable to metabolise NO, and the resulting strain was studied analysing its growth properties and oxygen uptake in the presence of NO. We here demonstrate that Ph-2/2HbO protects growth and cellular respiration of the heterologous host from the toxic effect of NO-donors. Unlike in Mycobacterium tuberculosis 2/2 HbN, the deletion of the N-terminal extension of Ph-2/2HbO does not seem to reduce the NO scavenging activity, showing that the N-terminal extension is not a requirement for efficient NO detoxification. Moreover, the ferric form of Ph-2/2HbO was shown to catalyse peroxynitrite isomerisation in vitro, confirming its potential role in the scavenging of reactive nitrogen species. This article is part of a Special Issue entitled: Oxygen Binding and Sensing Proteins.


Rheumatoid neutrophilic dermatitis.
Rheumatoid neutrophilic dermatitis (RND) is an infrequent cutaneous manifestation of rheumatoid arthritis (RA). This condition is seen in patients who are both positive and negative for a circulating rheumatoid factor. Histologically, it presents with a neutrophilic dermatosis, characterized by a heavy dermal infiltrate of neutrophils with variable degrees of leukocytoclasis but no vasculitis. We describe the case of a young female with seronegative RA who had concomitant lesions of RND over both elbows. Her lesions appeared as nodules, but RND has been reported as papules and plaques, sometimes with an urticarialike appearance or ulcerations. They are often symmetric. The possibility of RND should be considered in the differential of unusual skin lesions in all patients with RA, as the presentation is quite varied.


Nutritional assessment in preterm infants with special reference to body composition.
In recent years, improvements in care have significantly improved survival in preterm and, particularily, the very low birth weight infant (VLBW). While immediate survival can be directly related to pulmonary maturity, several studies stress the importance of timely and adequate nutrition in these high-risk infants on a short- and long-term [1]. Yet, nutritional support remains a very controversial issue in these high-risk infants. Early provision of adequate intakes may be limited by clinical instability and immaturity. At the same time, nutritional requirements and methods of nutritional assessment are not well defined. The aim of this paper is to outline some of the methods used during nutritional assessment in preterm infants with special reference to the measurement of body composition.


MTDeepM6A-2S: A two-stage multi-task deep learning method for predicting RNA N6-methyladenosine sites of Saccharomyces cerevisiae.
N6-methyladenosine (m6A) is one of the most important RNA modifications, which is involved in many biological activities. Computational methods have been developed to detect m6A sites due to their high efficiency and low costs. As one of the most widely utilized model organisms, many methods have been developed for predicting m6A sites of Saccharomyces cerevisiae. However, the generalization of these methods was hampered by the limited size of the benchmark datasets. On the other hand, over 60,000 low resolution m6A sites and more than 10,000 base resolution m6A sites of Saccharomyces cerevisiae are recorded in RMBase and m6A-Atlas, respectively. The base resolution m6A sites are often obtained from low resolution results by post calibration. In view of these, we proposed a two-stage deep learning method, named MTDeepM6A-2S, to predict RNA m6A sites of Saccharomyces cerevisiae based on RNA sequence information. In the first stage, a multi-task model with convolutional neural network (CNN) and bidirectional long short-term memory (BiLSTM) deep framework was built to not only detect the low resolution m6A sites but also assign a reasonable probability for the predicted site. In the second stage, a transfer-learning strategy was used to build the model to predict the base resolution m6A sites from those low resolution m6A sites. The effectiveness of our model was validated on both training and independent test sets. The results show that our model outperforms other state-of-the-art models on the independent test set, which indicates that our model holds high potential to become a useful tool for epitranscriptomics analysis.


Suicide and Maternal Mortality.
Suicide is a leading cause of death in the perinatal period (pregnancy and 1 year postpartum). We review recent findings on prevalence, risk factors, outcomes, and prevention and intervention for suicide during pregnancy and the first year postpartum. Standardization of definitions and ascertainment of maternal deaths have improved identification of perinatal deaths by suicide and risk factors for perinatal suicide. Reports of a protective effect of pregnancy and postpartum on suicide risk may be inflated. Clinicians must be vigilant for risk of suicide among their perinatal patients, especially those with mental health diagnoses or prior suicide attempts. Pregnancy and the year postpartum are a time of increased access to healthcare for many, offering many opportunities to identify and intervene for suicide risk. Universal screening for suicide as part of assessment of depression and anxiety along with improved access to mental health treatments can reduce risk of perinatal suicide.


Phonological processing skills in specific language impairment.
In order to provide effective intervention for children with specific language impairment (SLI), it is crucial that there is an understanding of the underlying deficit in SLI. This study utilized a battery of phonological processing tasks to compare the phonological processing skills of children with SLI to typically-developing peers matched for age or language. The children with SLI had significantly poorer performance than age-matched peers on measures of phonological representations, phonological awareness, rapid automatized naming, phonological short-term memory, and one measure of working memory. Of particular significance, the SLI group also demonstrated significantly weaker performance than language-matched peers on one measure of phonological representations, and one measure of working memory. The findings provide some support for a phonological processing account of SLI and highlight the utility of using tasks that draw on a comprehensive model of speech processing to profile and consider children's phonological processing skills in detail.


Joint molecular modeling and spectroscopic studies of DNA complexes of a bis(arginyl) conjugate of a tricationic porphyrin designed to target the major groove.
To target selectively the major groove of double-stranded B DNA, we have designed and synthesized a bis(arginyl) conjugate of a tricationic porphyrin (BAP). Its binding energies with a series of double-stranded dodecanucleotides, having in common a central d(CpG)2 intercalation site were compared. The theoretical results indicated a significant energy preference favoring major groove over minor groove binding and a preferential binding to a sequence encompassing the palindrome GGCGCC encountered in the Primary Binding Site of the HIV-1 retrovirus. Spectroscopic studies were carried out on the complexes of BAP with poly(dG-dC) and poly(dA-dT) and a series of oligonucleotide duplexes having either a GGCGCC, CCCGGG, or TACGTA sequence. The results of UV-visible and circular dichroism spectroscopies indicated that intercalation of the porphyrin takes place in poly(dG-dC) and all the oligonucleotides. Thermal denaturation studies showed that BAP increased significantly the melting temperature of the oligonucleotides having the GGCGCC sequence, whereas it produced only a negligible stabilization of sequences having CCCGGG or TACGTA in place of GGCGCC. This indicates a preferential binding of BAP to GGCGCC, fully consistent with the theoretical predictions. IR spectroscopy on d(GGCGCC)2 indicated that the guanine absorption bands, C6=O6 and N7-C8-H, were shifted by the binding of BAP, indicative of the interactions of the arginine arms in the major groove. Thus, the de novo designed compound BAP constitutes one of the very rare intercalators which, similar to the antitumor drugs mitoxantrone and ditercalinium, binds DNA in the major groove rather than in the minor groove.


Drug-eluting stents for the treatment of bifurcation lesions: a randomized comparison between paclitaxel and sirolimus stents.
Drug-eluting stents have been shown to reduce restenosis in many types of lesions. The purpose of this article is to assess the efficacy of sirolimus- and paclitaxel-eluting stents in patients with bifurcation lesions. Between June 2003 and October 2004, 205 patients were enrolled in a prospective randomized trial; 103 patients were assigned to sirolimus stents and 102 patients to paclitaxel stents. All patients were treated by provisional T-stenting. There were no differences between groups in terms of age, risk factors, clinical condition, location of the bifurcation lesion, or other technical factors. Angiographic data and immediate results were also similar in both groups. Three patients developed inhospital non-Q-wave acute myocardial infarction (2 from the sirolimus group and 1 from the paclitaxel group). Follow-up angiography was obtained in 109 patients (53%). In the sirolimus group, 5 patients developed restenosis (9%): 1 at the main vessel, 2 at the side branch, and 2 in both branches. In contrast, 16 patients from the paclitaxel group had restenosis (29%): 6 at the main vessel, 5 at the side branch, and 5 in both branches. Target lesion revascularization at 24 +/- 5 months post stenting occurred in 4 patients from the sirolimus group (4%) and in 13 from the paclitaxel group (13%) (P < .05). Late loss at the main vessel in the sirolimus group patients was 0.31 +/- 0.59 versus 0.60 +/- 0.77 mm in patients from the paclitaxel group (P < .05). Patients with bifurcation lesions treated by sirolimus showed significantly lower rates of late loss, restenosis and target lesion revascularization than patients treated with paclitaxel-eluting stents.


[Analysis of related risk factors for the refracture of adjacent vertebral body after percutaneous kyphoplasty].
To investigate the risk factors of vertebral refracture after percutaneous kyphoplasty (PKP) for osteoprotic vertebral compression fractures (OVCFs), and to provide reference for clinical prevention. A retrospective analysis of 228 OVCFs patients who met the inclusion criteria admitted from November 6, 2013 to December 14, 2018. There were 35 males and 193 females, with a male-to-female ratio of 3∶20, and aged 58 to 91 years with an average of (69.70±7.03) years. All patients were treated with PKP and had complete clinical data. According to whether refracture occurred after operation, they were divided into refracture group (24 cases) and non refracture group (204 cases). Factors that may be related to refracture (including gender, age, surgical segment, number of vertebral bodies in the surgical segment, whether combined with degenerative scoliosis, whether anti-osteoporosis treatment) were included in the univariate analyses, and the single factor analysis of statistically significant risk factors was carried out with multiple Logistic regression analysis to further clarify the independent risk factors for vertebral body refracture after PKP. Survival analysis was performed using the time of vertebral refracture after PKP as the end time of follow up, the occurrence of refracture after PKP as the endpoint event, and the presence or absence of degenerative lateral curvature as a variable factor. All 228 patients were followed up for 1.8 to 63.6 months with an average of (28.8±15.6) months, and the refracture rate was 10.5%(24/228). There were statistically significant differences between two groups in age, number of operative vertebral bodies, whether combinedwith degenerative scoliosis and whether anti osteoporosis treatment (P<0.05). Univariate Logistic regression analysis showed that the number of vertebral bodies in the surgical segment and whether combined with degenerative scoliosis may be risk factors for refracture after PKP. Multiple Logistic regression analysis of the above possible risk factors showed that combined scoliosis was an independent risk factor for vertebral refracture of the vertebral body. Survival analysis showed that the mean survival time was 42.1 months, the P value was 0.00, and the mean 95% confidence interval was 34.4-49.7 months, indicating that the combination of degenerative lateral bending might be related to the occurrence of refracture. Combined scoliosis is an independent risk factor for refracture after OVCFs vertebroplasty, and it is also a possible high-risk factor for refracture after surgery.


Ontogeny of the solitary chemosensory cells in the zebrafish, Danio rerio.
Secondary epidermal solitary chemosensory cells (SCCs) are widespread among the primary aquatic vertebrates. They resemble taste bud sensory cells in fine structure and may be innervated from facial or spinal nerves. According to previous studies, SCCs may constitute a water sampling system in the contexts of predator avoidance, habitat recognition and, in some cases, finding food. By quantitative scanning (SEM) and transmission electron microscopy (TEM) in 60 specimens (57 SEM, 3 TEM) of 16 developmental stages, from pre-hatchlings to adults, we describe the ontogenetic development of SCC densities and shapes of sensory apices in the zebrafish, Danio rerio. This is put into perspective with the ontogeny of external taste buds. Just prior to hatching, 3 days after fertilization (3d AF), sensory apices of SCCs penetrate between the squamous epidermal cells, whereas taste bud pores only appear at the onset of exogenous feeding (5d AF). SCC densities increase sharply from hatching shortly after metamorphosis (25d AF) up to 6 x 10(3) per mm2 on the head and remain relatively constant in density thereafter. Conservatively estimated, there may be approximately 3.2 x 10(5) SCCs on the head and 1 x 10(6) SCCs on the entire body surfaces of a zebrafish 180d AF. SCCs are spread evenly, but are 2- to 5-fold higher in density along the head than along the body. Sensory apices are brush-like in hatchlings and early juveniles, but tend to consist of a single villus in the adults. This ontogenetic change of SCC apices parallels the evolutionary change from 'oligovillous' cells in lampreys and elasmobranchs to the 'monovillous' SCCs in the advanced actinopterygian teleosts.


Measurement of total phospholipids in urine of patients treated with gentamicin.
The excretion of phospholipids in urine may be a marker of the early renal toxicity of the aminoglycoside antibiotics. Urinary phospholipids are formed in myeloid bodies which develop in the lysosomes of proximal tubules during treatment with the aminoglycosides, and overflow into the urine. Published assays were modified in order to measure the total phospholipid concentrations in human urine. Phospholipids were extracted from freeze-dried urine samples, digested in concentrated sulphuric acid, and the inorganic phosphorus content determined by complexing with ammonium molybdate and measuring the absorbance at 820 nm. Ten septicaemic patients treated with gentamicin for 5-7 days had significantly higher urine phospholipid concentrations than 10 healthy untreated control subjects (P < 0.0001). There was a negative linear relationship between phospholipid excretion and creatinine clearance (r2 = 0.71). In 34 patients with acute pyelonephritis, increased phospholipid concentrations were observed prior to treatment compared with healthy controls (P < 0.001) and did not alter during treatment with gentamicin. However, the phospholipid concentrations decreased significantly after treatment was completed (P < 0.03). These studies suggest that urinary phospholipids may indicate early aminoglycoside toxicity but with poor specificity, as many of the infections being treated may themselves be associated with phospholipiduria.


The molecular mechanism of regulation of the NhaA Na+/H+ antiporter of Escherichia coli, a key transporter in the adaptation to Na+ and H+.
The NhaA Na+/H+ antiporter is the main system responsible for adaptation to Na+ and alkaline pH (in the presence of Na+) in Escherichia coli and many other enteric bacteria. It is under intricate control. At the protein level it is regulated directly by pH, one of its regulatory signals. A pH shift from 7 to 8.5 activates the antiporter and, in a fashion correlated with the activity change, confers a conformation change that, in isolated membrane vesicles, is reflected in the exposure of trypsin-cleavable sites. H225 and G338 are essential for the pH response of NhaA. nhaA transcription is dependent on NhaR, a positive regulator of the LysR family, and is regulated by Na+, the other environmental signal. Na+ affects the NhaR/nhaA interaction directly by changing the footprint of NhaR on nhaA in a pH-dependent fashion. The expression of nhaA is also under global regulation of H-NS. We suggest that the pattern of regulation of nhaA found in E. coli is a paradigm for the response of proteins and genes to H+ and Na+, the most common ions that challenge every cell.


[Morphometry of the larynx in horizontal sections. Normal data for the quantitative evaluation of current imaging technics].
Laryngeal anomalies as a predisposing factor for pathogenesis of vocal disturbances have been discussed for a long time. Laryngeal structures can be made visible in vivo, and structural details be measured, only since the development of new imaging techniques, mainly of CT. As adequate descriptions have not been published in literature unto now, we measured horizontal sections of laryngeal specimens to collect reference data for a quantitative analysis of CT images. An evaluation technique was therefore developed, which, by clear definition of the planes and points of measurements, yields reproducible results. Direct measurement of the thyroid angles can be abandoned, since these can be easily calculated from the known distances.


18F-FDG-Labeled Autologous Leukocyte PET-CT in a Patient With Aortic Valve-Tube Graft Infection After Bentall Procedure.
Infection of aortic valve-tube graft, although rare, is associated with high morbidity and mortality. Early identification of site and extent of infection is not only challenging but also crucial for adequate patient management and prognostication of disease. Combined clinical, laboratory investigation and imaging modalities assist in the identification of aortic valve graft infection. Molecular imaging techniques like PET/CT using F-FDG and F-FDG-labeled autologous leukocytes (LALs) have improved the sensitivity for detection of infection, resulting in better outcome for these patients. F-FDG-labeled autologous leukocyte PET/CT in our patient after Bentall procedure accurately localized the site and extent of infection.


Differences in cardiac function changes between diabetic and non-diabetic hemodialysis patients.
The main cause of death in chronic hemodialysis patients is heart failure. We studied cardiac function prospectively in diabetic and non-diabetic patients who had recently been started on hemodialysis. We analyzed the mechanocardiograms and echocardiograms in addition to routine blood chemistry tests, chest X-rays, and electrocardiograms of ten hemodialysis patients at our hospital from 1989 to 1991. Ejection fraction (EF) and fractional shortening (FS) were not significantly different between diabetic patients and non-diabetic patients at the start of hemodialysis. After starting hemodialysis, EF and FS declined in diabetic patients. In contrast, non-diabetic patients did not show any changes in EF and FS during hemodialysis. The results demonstrated a poor prognosis in cardiac systolic function in hemodialysis patients with diabetes mellitus.


Crystal Structure of the Type VI Secretion System Accessory Protein TagF from Pseudomonas Aeruginosa.
Type VI Secretion System (T6SS) has been found in approximately onequarter of the gram-negative bacterial species, and its structural characteristics appear to slightly differ from species to species. The genes encoding T6SS are designated as type six secretion A-M (tssA-M). The expression of the tss gene cluster is regulated by various accessory genes, designated as type VI-associated genes A-P (tagA-P). Tag family proteins have been commonly found in bacteria expressing T6SS but not in all bacterial species. For instance, the tag gene cluster is well-conserved in Pseudomonas aeruginosa (Pa). The PaTagF protein has large homology with ImpM in Rhizobium leguminosarum and SciT in Salmonella enterica. The overexpression of PaTagF represses T6SS complex accumulation and suppresses T6SS antibacterial activity. Thus, the functions of TagF are mediated through direct interactions with the forkhead-associated protein Fha, as evident from the results of the yeast-two hybrid assays. Fha is involved in recruiting a membrane-associated complex either in threonine phosphorylation pathway-dependent or - independent manner. However, functional reports of the tag gene cluster are still limited. In this article, our motivation is to understand the molecular mechanism underlying the regulation of expression of the type VI secretion system complex. In this article, we start with obtaining the gene encoding PaTagF protein by polymerase chain reaction (PCR). Subsequently, the cloned gene is applied to overexpress of PaTagF protein in Escherichia coli, then purify the recombinant PaTagF protein. Thereafter, the protein is crystallized in a condition of 2.5 M NaCl, 0.1 M imidazole (pH 8.0), 3.2 M NaCl, 0.1 M BIS-TRIS propane (pH 7.0) and diffraction datasets of the PaTagF crystals are collected at the Pohang Accelerator Laboratory (PAL). The molecular structure of PaTagF protein is determined by molecular replacement using the uncharacterized protein PA0076 (PDB code:2QNU) as an initial search model by PHENIX crystallographic software package. Model building of PaTagF structure is performed using Coot program. Finally, the structural model is validated using phenix.refine program. PaTagF exists as a tetramer in the asymmetric unit, and the overall fold of each monomer is composed of continuous beta-sheets wrapped by alpha-helices. Each monomer has variable conformations and lengths of both the N- and C-termini. Twelve residues, including the His6 tag from the N-terminus of a symmetry-related molecule, have been found in two of the tetrameric PaTagF structures. A structural homology search revealed that PaTagF was similar to the α-β-α sandwichlike structure of the longin domain on the differentially expressed in normal and neoplastic (DENN) superfamily, which is commonly found in proteins related to trafficking. The tetrameric structure of PaTagF comprises varied N- and C-terminal regions in each subunit and may be stabilized by a symmetry-related molecule. This feature was also shown in the TssL structure from V. cholerae. Furthermore, our study showed that the overall fold of PaTagF is homologous to the longin domain of the DENN family. Therefore, further studies are warranted to elucidate the structure-based evolutionary relationship between protein transport systems from the bacteria and eukaryotic cells.


Transplantation of rat islets transduced with human heme oxygenase-1 gene using adenovirus vector.
To investigate whether human heme oxygenase-1 (HO-1) gene has protective action on islets cultured in vitro, and to explore whether transduction of HO-1 gene to donor islets could enhance engrafted islets survival and suppress local lymphocytic infiltration in islet grafts. Newly isolated rat islets were isolated from the Sprague-Dawley rats and were divided into 3 groups in vitro study as follows: enhanced green fluorescent protein (EGFP) group, islets transduced with adenovirus vectors containing EGFP gene using multiplicities of infection (MOI) = 2, 5, 10, and 20 to determine the transduction efficacy; HO-1 group, islets transduced with adenovirus vectors containing human HO-1 gene using MOI = 20; and control group, mock transduced islets. Flow cytometry was used to detect apoptotic cells after induction by recombinant human tumor necrosis factor-alpha (rTNF-alpha) and cycloheximide (CHX) for 48 hours. Diabetic recipients were randomly divided into the following groups: HO-1 group (n = 9), receiving islets transduced with recombinant adenovirus-HO-1; control group (n = 9), receiving mock transduced islets; and phosphate buffer solution (PBS) group (n = 6), receiving only 0.8 mL PBS. About 1200 rat islet equivalents were transplanted into each recipient rendered by streptozotocin using the portal vein as transplant site. Allograft survival, apoptosis, and the state of lymphocytic infiltration were analyzed. After treatment with rTNF-alpha and CHX, the apoptotic ratio of islet cells was 4.22% +/- 2.38% in the HO-1 group (MOI = 20), significantly lower than 23.81% +/- 8.51% in the control group (P < 0.05), and 28.76% +/- 14.76% in the EGFP group (MOI = 20; P < 0.05). Maintenance of normoglycemia was prolonged in the HO-1 group, indicated by results that islet survival time was 10.56 +/- 4.33 days significantly longer than that of untreated islets which was 5.33 +/- 4.18 days (P < 0.05). The lymphocytic infiltration degree in engrafted islets treated with HO-1 gene was lower than that in the control group. HO-1 gene overexpression in rat islets by adenovirus transduction can protect cultured islets against rTNF-alpha and CHX-mediated cytotoxicity. HO-1 gene has cytoprotective effects on engrafted islets, which could prolong engrafted islets survival in allogenic transplantation model, and diminish the degree of lymphocytic infiltration in islet grafts. These findings suggest a potential therapeutic application for HO-1 gene in improving islet survival/function in human islet transplantation.


The Use of a Sea Salt-based Spray for Diabetic Foot Ulcers: A Novel Concept.
Several patients present to wound healing specialists seeking a natural or alternative medical approach to their wounds. The purpose of this prospective, case-cohort study of 10 patients was to evaluate the use of Oceanzyme Wound Care Spray (Ocean Aid, Inc, Boynton Beach, FL) in improving healing in diabetic foot ulcers during a 12-week period. This product contains water purified by reverse osmosis, coral reef sea salt, lysozyme, and sodium benzoate. The primary endpoint was wound closure, and secondary endpoints were infection rate and wound area reduction. Overall, 2 patients healed, 2 withdrew, and the remaining 6 had an average of 73% reduction in wound area. While more study is needed, the use of this sea salt-based spray may provide a viable alternative for patients seeking a natural therapy for their wound care.


Influence of processing conditions on apparent viscosity and system parameters during extrusion of distiller's dried grains-based snacks.
A combination of different levels of distillers dried grains processed for food application (FDDG), garbanzo flour and corn grits were chosen as a source of high-protein and high-fiber extruded snacks. A four-factor central composite rotatable design was adopted to study the effect of FDDG level, moisture content of blends, extrusion temperature, and screw speed on the apparent viscosity, mass flow rate or MFR, torque, and specific mechanical energy or SME during the extrusion process. With increase in the extrusion temperature from 100 to 140°C, apparent viscosity, specific mechanical energy, and torque value decreased. Increase in FDDG level resulted in increase in apparent viscosity, SME and torque. FDDG had no significant effect (p > .5) on mass flow rate. SME also increased with increase in the screw speed which could be due to the higher shear rates at higher screw speeds. Screw speed and moisture content had significant negative effect (p < .05) on the torque. The apparent viscosity of dough inside the extruder and the system parameters were affected by the processing conditions. This study will be useful for control of extrusion process of blends containing these ingredients for the development of high-protein high-fiber extruded snacks.


Effects of horticultural therapy on mood and heart rate in patients participating in an inpatient cardiopulmonary rehabilitation program.
To assess the effects of horticultural therapy (HT) on mood state and heart rate (HR) in patients participating in an inpatient cardiac rehabilitation program. Cardiac rehabilitation inpatients (n = 107) participated in the study. The HT group consisted of 59 subjects (34 males, 25 females). The control group, which participated in patient education classes (PECs), consisted of 48 subjects (31 males, 17 females). Both HT sessions and PEC are components of the inpatient rehabilitation program. Each group was evaluated before and after a class in their respective modality. Evaluation consisted of the completion of a Profile of Mood States (POMS) inventory, and an HR obtained by pulse oximetry. Changes in the POMS total mood disturbance (TMD) score and HR between preintervention and postintervention were compared between groups. There was no presession difference in either TMD score (16 +/- 3.6 and 19.0 +/- 3.2, PEC and HT, respectively) or HR (73.5 +/- 2.5 and 79 +/- 1.8, PEC and HT, respectively). Immediately following the intervention, the HT TMD was significantly reduced (post-TMD = 1.6 +/- 3.2, P < .001), while PEC TMD was not significantly changed (TMD = 17.0 +/- 28.5). After intervention, HR fell in HT by 4 +/- 9.6 bpm (P < .001) but was unchanged in PEC. These findings indicate that HT improves mood state, suggesting that it may be a useful tool in reducing stress. Therefore, to the extent that stress contributes to coronary heart disease, these findings support the role of HT as an effective component of cardiac rehabilitation.


Diet quality, overweight and daily monetary allowance of Greek adolescents.
Objective To investigate cross-correlates of pocket-money on diet quality and weight status of Greek adolescents. Methods A total of 172 adolescents (55.2% boys), aged between 10 and 15 years old were recruited. Body weight and height were measured, body mass index (BMI) was computed. Weight status was assessed according to the International Obesity Task Force criteria and diet quality was evaluated via the Healthy Eating Index (HEI) - 2010. Results Adolescents were allowed a mean allowance of €4.63 ± 3.66 daily. Among boys participants, BMI correlated with pocket money (r = 0.311, p ≤ 0.002) and normoweight boys received statistically less money than their overweight peers (p ≤ 0.019). In both sexes, normoweight was more prevalent in the lowest monetary quartiles. Pocket money was not associated with HEI. Among boys, moderate HEI was more prevalent in the third quartile of pocket money, significantly higher compared to all others (p ≤ 0.01 for all). For girls, the prevalence of moderate HEI declined by each ascending pocket money quartile (p ≤ 0.05 for all). Conclusion In our sample, adolescents exhibited high rates of pooled overweight including obesity. The majority of the participants followed a diet of moderate quality. Pocket money was associated with BMI only among boys. As pocket money was not associated with diet quality, it is highly possible that adolescents might choose to spend their money on items other than foods. Our study shows that pocket money should be controlled during adolescence and teenagers should be educated on spending their money on healthier food choices.


Nasopharyngeal recordings separate retinal from optic nerve potentials.
Electrical potentials in response to single flashes and to pattern-reversal stimuli presented in Maxwellian view were recorded from several intranasal locations by withdrawing a nasopharyngeal electrode from the epipharynx through the nose in steps of 1 cm. From the anterior parts of the nose a waveform could be obtained resembling the corneal electroretinogram. In the epipharynx an ERG was recorded which was inverted in polarity. This reversal in polarity was explained by assuming an electrical dipole of the retina oriented parallel to the electrode path. When the electrode was below and behind the posterior pole of the eye ball a high-frequency activity of increased amplitude was observed the origin of which could not be explained by the retinal dipole. It is suggested that these increased oscillations originate from the optic nerve. Their behavior is explained by a hypothetical electrical dipole of the optic nerve oriented vertical to the electrode path.


Development and Evaluation of Monoclonal Antibodies for Paxilline.
Paxilline (PAX) is a tremorgenic mycotoxin that has been found in perennial ryegrass infected with Acremonium lolii. To facilitate screening for this toxin, four murine monoclonal antibodies (mAbs) were developed. In competitive indirect enzyme-linked immunosorbent assays (CI-ELISAs) the concentrations of PAX required to inhibit signal development by 50% (IC50s) ranged from 1.2 to 2.5 ng/mL. One mAb (2-9) was applied to the detection of PAX in maize silage. The assay was sensitive to the effects of solvents, with 5% acetonitrile or 20% methanol causing a two-fold or greater increase in IC50. For analysis of silage samples, extracts were cleaned up by adsorbing potential matrix interferences onto a solid phase extraction column. The non-retained extract was then diluted with buffer to reduce solvent content prior to assay. Using this method, the limit of detection for PAX in dried silage was 15 µg/kg and the limit of quantification was 90 µg/kg. Recovery from samples spiked over the range of 100 to 1000 µg/kg averaged 106% ± 18%. The assay was applied to 86 maize silage samples, with many having detectable, but none having quantifiable, levels of PAX. The results suggest the CI-ELISA can be applied as a sensitive technique for the screening of PAX in maize silage.


[The morbidity and mortality of adult population because of diseases of blood circulation system].
The article presents comparative results of analysis of morbidity and mortality in the Omskaia oblast and data of official statistics of the Russian Federation and the Sibirskii federal okrug. The regional characteristics are revealed concerning morbidity of adult population with diseases of blood circulation system.


Catamenial pneumothorax.
A report is given of a 46-year-old woman, who had nine recurrencies of a catamenial right-sided pneumothorax. During anovulatory hormone treatment no recurrency was noted for the following 6 months.


Dual HER2 Blockade Helps Prevent Breast Cancer Return.
Adding pertuzumab to an adjuvant regimen of trastuzumab for women with early-stage HER2+ breast cancer reduces the risk of disease recurrence, especially among those with node-positive and hormone receptor-negative disease. Results from the phase III APHINITY trial, which could help pertuzumab earn full approval for this indication, were presented at the 2017 American Society of Clinical Oncology Annual Meeting.


Foam cell specific LXRα ligand.
The liver X receptor α (LXRα) is a ligand-dependent nuclear receptor and the major regulator of reverse cholesterol transport in macrophages. This makes it an interesting target for mechanistic study and treatment of atherosclerosis. We optimized a promising stilbenoid structure (STX4) in order to reach nanomolar effective concentrations in LXRα reporter-gene assays. STX4 displayed the unique property to activate LXRα effectively but not its subtype LXRβ. The potential of STX4 to increase transcriptional activity as an LXRα ligand was tested with gene expression analyses in THP1-derived human macrophages and oxLDL-loaded human foam cells. Only in foam cells but not in macrophage cells STX4 treatment showed athero-protective effects with similar potency as the synthetic LXR ligand T0901317 (T09). Surprisingly, combinatorial treatment with STX4 and T09 resulted in an additive effect on reporter-gene activation and target gene expression. In physiological tests the cellular content of total and esterified cholesterol was significantly reduced by STX4 without the undesirable increase in triglyceride levels as observed for T09. STX4 is a new LXRα-ligand to study transcriptional regulation of anti-atherogenic processes in cell or ex vivo models, and provides a promising lead structure for pharmaceutical development.


The use of monoclonal antibody B72.3 in the management of gynecologic malignancies.
Monoclonal antibodies are currently used in the diagnosis of gynecologic malignancies by way of immunohistochemical assays, serum assays, and in situ radiolocalization of carcinoma lesions. Among them is MAb B72.3, generated against a human tumor-associated antigen (TAG-72). Using immunohistochemical techniques, MAb B72.3 has shown reactivity with 100 percent of common epithelial ovarian carcinomas and endometrial carcinomas and non-reactivity with normal adult tissues, with the exception of normal secretory endometrium. B72.3 appears to be a valuable immunocytologic adjunct, with greater than 90 percent of effusions and fine-needle aspiration biopsies from gynecologic carcinomas showing reactivity. Using a serum assay developed to detect the presence of the TAG-72 antigen, 48 percent of patients with ovarian carcinoma demonstrated TAG-72-positive sera versus 1 percent of control sera. 131I-labeled MAb B72.3 IgG and gamma scanning have been used for the in situ detection of metastatic carcinoma. Twelve of 15 patients with ovarian carcinoma showed positive gamma scans, and approximately 80 percent of the lesions demonstrated specific localization of the antibody. These studies indicate the potential utility of MAb B72.3 in the diagnosis of gynecologic carcinoma.


Immunopathogenesis in hepatitis C virus cirrhosis.
HCV (hepatitis C virus) has a high propensity to persist and to cause chronic hepatitis C, eventually leading to cirrhosis. Since HCV itself is not cytopathic, liver damage in chronic hepatitis C is commonly attributed to immune-mediated mechanisms. HCV proteins interact with several pathways in the host's immune response and disrupt pathogen-associated pattern recognition pathways, interfere with cellular immunoregulation via CD81 binding and subvert the activity of NK (natural killer) cells as well as CD4(+) and CD8(+) T-cells. Finally, HCV-specific T-cells become increasingly unresponsive and apparently disappear, owing to several possible mechanisms, such as escape mutations in critical viral epitopes, lack of sufficient help, clonal anergy or expansion of regulatory T-cells. The role of neutralizing antibodies remains uncertain, although it is still possible that humoral immunity contributes to bystander damage of virally coated cells via antibody-dependent cellular cytotoxicity. Cytotoxic lymphocytes kill HCV-infected cells via the perforin/granzyme pathway, but also release Fas ligand and inflammatory cytokines such as IFNgamma (interferon gamma). Release of soluble effector molecules helps to control HCV infection, but may also destroy uninfected liver cells and can attract further lymphocytes without HCV specificity to invade the liver. Bystander damage of these non-specific inflammatory cells will expand the tissue damage triggered by HCV infection and ultimately activate fibrogenesis. A clear understanding of these processes will eventually help to develop novel treatment strategies for HCV liver disease, independent from direct inhibition of HCV replication.


Enhancement of host resistance against Salmonella typhimurium infection by a diet supplemented with yogurt.
The effect of a diet supplemented with yogurt containing live lactobacilli (LAB) - Lactobacillus bulgaricus and Streptococcus thermophilus - on the response of inbred mice to infection with Salmonella typhimurium was elaborated. The results of our experiments were consistent with the hypothesis that modifications of the microflora influence the adherence of S. typhimurium to intestinal mucosa, the natural antibacterial activity of the Peyer's patches lymphocytes, the accumulation of the macrophages in the liver, the proliferative responses of the splenocytes. The relationship between modifications of the immune response following ingestion of yogurt with live LAB and increased defense mechanisms was confirmed by the bacterial counts in livers and spleens and by the reduced mortality to S. typhimurium infection.


Fibrinogen concentrate for acquired hypofibrinogenaemic states.
This study aims to assess the efficacy and safety of fibrinogen concentrate in acquired hypofibrinogenaemic states. Cryoprecipitate is standard treatment for replacement of fibrinogen in acquired hypofibrinogenaemia. A virally inactivated fibrinogen concentrate (Haemocomplettan((R)); CSL Behring, Marburg, Germany) is licensed in some European countries. Clinical data for its use in acquired hypofibrinogenaemic states are scarce. Demographic and pretreatment clinical data of patients treated with fibrinogen concentrate for acquired hypofibrinogenaemia were retrospectively reviewed. Pretreatment and posttreatment fibrinogen levels, transfusion requirements, outcomes and adverse events were recorded. Thirty adult patients who received fibrinogen concentrate for acquired hypofibrinogenaemia (fibrinogen <1.5 g L(-1)) were included in the study. Causes of hypofibrinogenaemia included placental abruption, disseminated intravascular coagulation as a result of massive blood loss and transfusion, liver failure and cardiac surgery. Following a median dose of 4 g fibrinogen concentrate, median Clauss fibrinogen level rose from 0.65 to 2.01 g L(-1), with a median fibrinogen increment of 0.25 g L(-1) per 1 g fibrinogen concentrate administered. Forty-six per cent of patients stopped bleeding with blood components and fibrinogen concentrate alone, and a further 29% stopped bleeding with surgical or endoscopic intervention. Inpatient mortality was 40%. No venous thromboses were observed. Four patients with massive perioperative haemorrhage and hypotension (including three postcardiothoracic surgery) had arterial ischaemic events, none of which was attributable to fibrinogen overreplacement. The cost of fibrinogen concentrate was comparable with that of cryoprecipitate. Purified, virally inactivated fibrinogen concentrate appears effective in the management of acquired hypofibrinogenaemic states and enables rapid administration of a known fibrinogen dose in an emergency setting.


In-vitro antitumor activity evaluation of hyperforin derivatives.
The derivatives of hyperforin, namely hyperforin acetate (2), 17,18,22,23,27,28,32,33-octahydrohyperforin acetate (3), and N,N-dicyclohexylamine salt of hyperforin (4), have been investigated for their antitumor properties. In-vitro studies demonstrated that 2 and 4 were active against HeLa (human cervical cancer), A375 (human malignant melanoma), HepG2 (human hepatocellular carcinoma), MCF-7 (human breast cancer), A549 (human nonsmall cell lung cancer), K562 (human chronic myeloid leukemia), and K562/ADR (human adriamycin-resistant K562) cell lines with IC(50) values in the range of 3.2-64.1 μM. The energy differences between highest occupied molecular orbital and lowest unoccupied molecular orbital of 2-4 were calculated to be 0.39778, 0.43106, and 0.30900 a.u., respectively, using the Gaussian 03 software package and ab initio method with the HF/6-311 G* basis set. The result indicated that the biological activity of 4 might be the strongest and that of 3 might be the weakest, which was in accordance with their corresponding antiproliferative effects against the tested tumor cell lines. Compound 4 caused cell cycle arrest at G2/M phase in flow cytometry experiment and induced apoptosis by 4',6-diamidino-2-phenylindole staining and Annexin V-FITC/PI (propidium iodide) double-labeled staining in HepG2 cells. The results indicated a potential for N,N-dicyclohexylamine salt of hyperforin as a new antitumor drug.


Schizophrenia, autoimmunity and immune system dysregulation: a comprehensive model updated and revisited.
Recent investigation suggests a strong relationship between immunological effects and the pathophysiology of schizophrenia. Two prevalent approaches exist to this association. First, is more empirical a-priori research investigating immunological changes prevalent in schizophrenia and the second approach is more hypothesis-driven with analysis of immunological changes in schizophrenia based on known irregularities of the illness. The former approach is based upon three predominant lines of investigation including observations of a diffuse non-specific overactivation of the immunological response system, of a T-helper cell type 1 immune activation and of a T-helper cell type 2 immune activation in subgroups of schizophrenia patients. These last two theories suggest that a subgroup of patients with schizophrenia may demonstrate features of an autoimmune process, a theory supported by a growing database of investigation. The latter approach notes that many observations of immune dysregulation in schizophrenia overlap with central etiopathophysiological mechanisms as well as with clinical manifestations of the illness. Immunotherapy offers the opportunity to modify or re-balance the immune system and may become useful in management of the illness. Given that autoimmune mechanisms could interrupt neurotransmission, any process interfering with this disruption including therapeutic antibodies to involved cytokines, or with various other natural autoantibodies or immune system regulators, may become useful in the augmentative management of the illness.


Single-sex infection with female Schistosoma mansoni cercariae mitigates hepatic fibrosis after secondary infection.
Infection with Schistosoma spp. affects more than 258 million people worldwide. Current treatment strategies are mainly based on the anthelmintic Praziquantel, which is effective against adult worms but neither prevents re-infection nor cures severe liver damage. The best long-term strategy to control schistosomiasis may be to develop an immunization. Therefore, we designed a two-step Schistosoma mansoni infection model to study the immune-stimulating effect of a primary infection with either male or female cercariae, measured on the basis of TH1/TH2-response, granuloma size and hepatic fibrosis after a secondary bisexual S. mansoni challenge. As a first step, mice were infected with exclusively female, exclusively male, or a mixture of male and female S. mansoni cercariae. 11 weeks later they were secondarily infected with male and female S. mansoni cercariae. At week 19, infection burden, granuloma size, collagen deposition, serum cytokine profiles and the expression of inflammatory genes were analyzed. Mice initially infected with female S. mansoni cercariae displayed smaller hepatic granulomas, livers and spleens, less hepatic fibrosis and higher expression of Ctla4. In contrast, a prior infection with male or male and female S. mansoni did not mitigate disease progression after a bisexual challenge. Our findings provide evidence that an immunization against S. mansoni is achievable by exploiting gender-specific differences between schistosomes.


Surviving the Holocaust: Socio-demographic Differences Among Amsterdam Jews.
This study determined the victimisation rate among Amsterdam Jews and socio-demographic differences in surviving the Holocaust. After linking a registration list of over 77,000 Jewish inhabitants in 1941 to post-war lists of Jewish victims and survivors, the victimisation rate lies between 74.3 and 75.3 %. Differences in survival chances and risk of being killed are examined by using multivariable logistic and Cox regression analyses. While male Jews had a reduced risk of death, in the end their survival chances hardly differed from females. Though Jews aged 6-14 and 31-50 initially had a lower risk of death, in the end compared with Jews aged 15-30 they had lower survival chances, just as Jews aged 50+. For Jews aged 0-5, it was the other way around. Immigrants showed better survival chances than native Jews. German Jews showed better survival chances than Dutch Jews, but Polish and other Jewish nationals showed highest survival chances. Jews who had abandoned Judaism had better survival chances than Jews belonging to an Israelite congregation. Divorced, widowed and unmarried adult Jews had better survival chances than married Jews and their children; Jews married to non-Jews, however, had one of the highest survival chances. Jews in the two highest social classes had better survival chances than jobless Jews. These findings indicate that survival was not random but related to socio-demographic characteristics. This sheds light on demographic consequences of conflict and violence: Nazi persecution reduced the Amsterdam Jewish community drastically, and socio-demographic differences in survival impacted the post-war Jewish population structure.


Cardiovascular problems in the diabetic patient.
Diabetes therapy is no longer about glucose lowering per se, but about overall reduction in risk factors for diabetic complications. Diabetes doubles the risk of developing CVD in men and almost triples it in women.


A comparison of neuroimaging findings in childhood onset schizophrenia and autism spectrum disorder: a review of the literature.
Autism spectrum disorder (ASD) and childhood onset schizophrenia (COS) are pediatric neurodevelopmental disorders associated with significant morbidity. Both conditions are thought to share an underlying genetic architecture. A comparison of neuroimaging findings across ASD and COS with a focus on altered neurodevelopmental trajectories can shed light on potential clinical biomarkers and may highlight an underlying etiopathogenesis. A comprehensive review of the medical literature was conducted to summarize neuroimaging data with respect to both conditions in terms of structural imaging (including volumetric analysis, cortical thickness and morphology, and region of interest studies), white matter analysis (include volumetric analysis and diffusion tensor imaging) and functional connectivity. In ASD, a pattern of early brain overgrowth in the first few years of life is followed by dysmaturation in adolescence. Functional analyses have suggested impaired long-range connectivity as well as increased local and/or subcortical connectivity in this condition. In COS, deficits in cerebral volume, cortical thickness, and white matter maturation seem most pronounced in childhood and adolescence, and may level off in adulthood. Deficits in local connectivity, with increased long-range connectivity have been proposed, in keeping with exaggerated cortical thinning. The neuroimaging literature supports a neurodevelopmental origin of both ASD and COS and provides evidence for dynamic changes in both conditions that vary across space and time in the developing brain. Looking forward, imaging studies which capture the early post natal period, which are longitudinal and prospective, and which maximize the signal to noise ratio across heterogeneous conditions will be required to translate research findings into a clinical environment.


Expression of microsomal prostaglandin E synthase-1 in intestinal type gastric adenocarcinoma and in gastric cancer cell lines.
Gastrointestinal carcinomas synthesize elevated levels of prostaglandin E(2) (PGE(2)), which has been mechanistically linked to carcinogenesis. Recently, microsomal prostaglandin E synthase-1 (mPGES-1) was cloned, which seems to be inducible and linked to cyclooxygenase-2 (Cox-2) in the biosynthesis of PGE(2). We examined expression of mPGES-1 in intestinal type gastric adenocarcinomas and in gastric cancer cell lines. The transcript for mPGES-1 was elevated in 57% (4/7) of gastric carcinomas as detected by Northern blot analysis. Moderate to strong mPGES-1 immunoreactivity was observed in 56% (5/9) of the carcinomas as detected by immunohistochemistry. Furthermore, mPGES-1 mRNA, protein and microsomal PGES activity were detected in gastric adenocarcinoma cell lines that originated from intestinal type tumors (MKN-7 and MKN-28). In contrast to Cox-2, however, expression of mPGES-1 mRNA or protein were not induced by phorbol 12-myristate 13-acetate (PMA) or interleukin-1beta (IL-1beta) in any of the gastric cancer cell lines tested (MKN-1, -7, -28, -45 and -74). Two gastric cancer cell lines (MKN-45 and MKN-74) did not express mPGES-1 and lacked microsomal PGES activity, but were still able to synthesize PGE(2). Because all gastric cell lines expressed cPGES as detected by immunoblotting, it is possible that Cox-2 can interact with cPGES or with some other yet unidentified PGES in gastric cancer cells. Furthermore, our data show that regulatory mechanisms that drive expression of mPGES-1 and Cox-2 dissociate in gastric cancer cell lines.


Intelligent based hybrid renewable energy resources forecasting and real time power demand management system for resilient energy systems.
The rapid growth of hybrid renewable Distributed Energy Resources (DERs) generation possess various challenges with inaccurate forecast models in stochastic power systems. The prime objective of this research is to maximum utilization of scheduled power from hybrid renewable based DERs to maintain the load-demand profile with reduce distributed grid burden. The proposed mixed input-based cascaded artificial neural network (CANNMF) is realized for the prediction of a short-term based hourly solar irradiance and wind speed. The testing approach is performed through a historical hourly dataset of the proposed site. Further, the normalized data sets are divided into hourly-based samples for validating the load demand power with respect to the variation in metrological data. In this paper, Adaptive Neuro-Fuzzy Inference System (ANFIS) model is simulated for short-term power demand prediction. This adaptive methodology is an effective approach for load-demand management which is based on cross-entropy. It also confirmed that during testing, the forecasting mean error and cross-entropy are less than 5% under a specific time slap of an individual day. The regression analysis is performed through the time series fitting simulation tool at different time horizons. The performance evaluation of the designed model is compared with the multi-layer perceptron model. Simulation results display the proposed mixed input-based cascaded system has enhanced accuracy and optimal performance than the multi-output correlated perceptron model.


NMR studies in experimental allergic encephalomyelitis: factors which contribute to T1 and T2 values.
To determine the factors which may alter NMR relaxation times in multiple sclerosis (MS) lesions we measured the proton T1 and T2, specific gravity (SG), and histology in the central nervous system (CNS; 13-19 levels per animal) in the myelin basic protein (MBP) and CNS-induced acute and relapsing EAE models in 44 juvenile Hartley guinea pigs. In the MBP model, T1 is unchanged but T2 is prolonged before symptoms and pathological changes occur. T2 remains prolonged during the acute phase of MBP-induced EAE. In the acute CNS model, T1 and T2 were not different from control despite advanced pathological changes of inflammation and demyelination and changes in specific gravity, indicating a marked change in tissue water content. No single variable, pathological or SG, could predict T1 or T2 values in the CNS-induced model. In active disease in the MBP model, when edema occurs in the presence or absence of parenchymal infiltration, T2 values are increased. However, as the factors which influence tissue NMR characteristics are complex in these MS models, it is likely difficult to infer specific pathological events from MRI findings in patients with MS.


Long distance neonatal transport--the need of the hour.
This study compares the inter hospital long distance transports undertaken by a qualified transport team versus those done by other means. This was a retrospective descriptive comparative study of the neonatal transports done during a period of 33 months from various maternity and pediatric centers to a pediatric tertiary referral centre. We found that biochemical and temperature disturbances are more common in babies transported on their own and a specialized neonatal transport service could improve the survival of these babies. Survival was 96.2% (154/160) and 89% (114/128) in the two groups, respectively (P=0.03).


Centrifugation-induced water-tunable photonic colloidal crystals with narrow diffraction bandwidth and highly sensitive detection of SCN-.
Novel opal hydrogels with water-tunable photonic bandgap (PBG) exhibiting responses to external stimuli were self-assembled from polystyrene-co-poly(N,N-dimethylacrylamide) (PS-co-PDMAA) microspheres. The polymeric microspheres with narrow size distribution were successfully prepared in water, consisting of two regions. The inner region is rich in PS which is hard and hydrophobic; the outer region is rich in PDMAA which is soft and hydrophilic. The self-assembly of the PS-co-PDMAA hydrogel microspheres is ready induced by centrifugation and resulted in highly ordered three-dimensional (3D) photonic colloidal crystals (PCCs). With an increase of the amount of water, the PBG of the opal hydrogels shifted from the visible to near-infrared region of the electromagnetic spectrum. The maximum shift of diffraction peak positions could be larger than 500 nm with narrow full width at half maximum (FWHM) in the range of 20 to 40 nm only. The change in color was visible to the naked eye. The remarkable sensitivity to water of the lattice spacing of the opal hydrogels was repeatable after centrifugation. These observations are attributed to a reproducible degree of hydration of the hydrophilic outer region of the polymeric microspheres. Furthermore, the diffraction of the opal hydrogels was particularly sensitive to the presence of thiocyanate (SCN(-)) ions. The interaction between SCN(-) ions and DMAA repeat units is argued to block hydrogen bonds between DMAA and water molecules. Our PS-co-PDMAA opal hydrogels could be a practical system for diffraction-based detections.


Tanshinone IIA Improves Painful Diabetic Neuropathy by Suppressing the Expression and Activity of Voltage-Gated Sodium Channel in Rat Dorsal Root Ganglia.
Painful diabetic neuropathy (PDN) is one of the intractable complications of diabetes mellitus, which manifest as exaggerated pain perception. Previous studies showed that Tanshinone IIA (TIIA), one of the major bioactive extracts of Salvia miltiorrhiza Bunge, have obvious analgesic effect on different types of pain process, and the underlying analgesic mechanisms are not fully understood. The present study combined the behavioral, electrophysiological and biochemical methods to elucidate the analgesic mechanism of TIIA, using streptozotocin (STZ)-induced PDN rat models. Intraperitoneal injection (i.p.) of TIIA for 3 weeks in PDN rats significantly improved mechanical allodynia and thermal hyperalgesia. Patch clamp recordings showed that the excitability of dorsal root ganglion (DRG) nociceptive neuron was increased in diabetic state, and TIIA treatment effectively recovered the subnormality, which was achieved by preventing augments of both Tetrodotoxin-sensitive (TTX-resistant) and Tetrodotoxin-sensitive (TTX-S) sodium currents. Further, the protein expressions of voltage-gated sodium channels (VGSCs) α-subunits Nav1.3, Nav1.7 and Nav1.9 increased in DRG of diabetic rats and were normalized by TIIA application. In conclusion, this study provides evidence that the TIIA attenuated PDN by effecting VGSCs activities and expressions, indicating that the TIIA could be a promising agent for PDN treatment.


Duodenal ulcer and pancreatitis associated with pancreatic arteriovenous malformation.
Arteriovenous malformation (AVM) of the pancreas is a rare condition that may cause severe gastrointestinal bleeding. We describe a 54-year-old man with a 7-year history of recurrent duodenal ulcer due to AVM in the pancreatic head. We recommended pancreatoduodenectomy because of recurrent haemorrhage from the duodenal ulcer, but the patient refused surgery on several occasions. He was admitted to our hospital complaining of severe upper abdominal pain radiating to the back and was diagnosed with acute pancreatitis. He agreed at that stage to the surgical treatment. The resected specimen contained a highly vascular malformation in the pancreatic head and ulceration in the adjacent descending duodenum. Histopathological examination revealed numerous vascular structures with dilated and tortuous vessels in the pancreatic head, confirming the presence of AVM. Moreover, oedema, inflammatory cell infiltration, haemorrhage and necrosis were evident, confirming the presence of acute pancreatitis.


Organ transplantation: contemporary Sunni Muslim legal and ethical perspectives.
The problems that organ transplantation poses to the Muslim mind may be summarized as follows: firstly, a Muslim believes that whatever he owns or possesses has been given to him as an amanah (trust) from Allah. Would it not be a breach of trust to give consent for the removal of parts of one's body, while still alive, for transplantation to benefit one's child, sibling or parent? Secondly, the Shari'ah (Islamic Law) emphasizes the sacredness of the human body. Would it not then be an act of aggression against the human body, tantamount to its mutilation, if organs were to be removed after death for the purpose of transplantation? In this paper I attempt to illustrate how the Muslim jurists have tried to resolve the dilemma of Muslims by providing them with certain guidelines based on the original sources of Islam, namely, the Qur'an and the Prophetic tradition. In order to assist the followers of other religious traditions to grasp the gravity of the problem posed by organ transplantation to the Muslim mind, I begin by discussing the opinions of Muslim jurists on the issue of utilization of human parts. Thereafter, I touch upon the resolutions taken by the various Islamic Juridical Academies on the issue in question. Finally, I shed light upon the inclusion of organ donation in a Muslim Will and the enforceable nature of such a will.


Cannabinoid receptor 2 deletion influences social memory and synaptic architecture in the hippocampus.
Although the cannabinoid receptor 2 (CB2R) is often thought to play a role mainly outside the brain several publications unequivocally showed the presence of CB2R on hippocampal principal neurons. Activation of CB2R produced a long-lasting membrane potential hyperpolarization, altered the input/output function of CA2/3 principal neurons and produced alterations in gamma oscillations. However, other cellular, molecular and behavioral consequences of hippocampal CB2R signaling have not been studied in detail. Here we demonstrate that the deletion of CB2 leads to a highly significant increase in hippocampal synapsin-I expression levels and particle density, as well as increased vesicular GABA transporter (vGAT) levels. This phenotype was restricted to females and not observed in males. Furthermore, we demonstrate an impairment of social memory in CB2 deficient mice. Our results thus demonstrate that the lack of CB2R leads to changes in the hippocampal synaptic landscape and reveals an important sex-specific difference in endocannabinoid signaling. This study supports a significant role of the CB2R in modulation of different types of memory despite its low expression levels in the brain and provides more insight into a sex-specific role of CB2R in synaptic architecture.


Involvement of CYP2A6 in the formation of a novel metabolite, 3-hydroxypilocarpine, from pilocarpine in human liver microsomes.
Pilocarpine is a cholinergic agonist that is metabolized to pilocarpic acid by serum esterase. In this study, we discovered a novel metabolite in human urine after the oral administration of pilocarpine hydrochloride, and we investigated the metabolic enzyme responsible for the metabolite formation. The structure of the metabolite was identified as 3-hydroxypilocarpine by liquid chromatography-tandem mass spectrometry and NMR analyses and by comparing to the authentic metabolite. To clarify the human cytochrome P450 (P450) responsible for the metabolite formation, in vitro experiments using P450 isoform-selective inhibitors, cDNA-expressed human P450s (Supersomes; CYP1A2, -2A6, -2B6, -2C9, -2C19, -2D6, -2E1, and -3A4), and liver microsomes from different donors were conducted. The formation of 3-hydroxypilocarpine in human liver microsomes was strongly inhibited (>90%) by 200 microM coumarin. Other selective inhibitors of CYP1A2 (furafylline and alpha-naphthoflavone), CYP2C9 (sulfaphenazole), CYP2C19 [(S)-mephenytoin], CYP2E1 (4-methylpyrazole), CYP2D6 (quinidine), and CYP3A4 (troleandomycin) had a weak inhibitory effect (<20%) on the formation. The highest formation activity was expressed by recombinant CYP2A6. The K(m) value for recombinant CYP2A6 was 3.1 microM, and this value is comparable with that of human liver microsomes (1.5 microM). The pilocarpine 3-hydroxylation activity was correlated with coumarin 7-hydroxylation activity in 16 human liver microsomes (r = 0.98). These data indicated that CYP2A6 is the main enzyme responsible for the 3-hydroxylation of pilocarpine. In conclusion, we identified a novel metabolite of pilocarpine, 3-hydroxypilocarpine, and we clarified the involvement of CYP2A6 in the formation of this molecule in human liver microsomes.


Primary male osteoporosis is associated with enhanced glucocorticoid availability.
While systemic glucocorticoids compromise bone metabolism, altered intracellular cortisol availability may also contribute to the pathogenesis of primary male osteoporosis (MO). The objective of this study was to assess whether intracellular cortisol availability is increased in MO due to a distorted local cortisol metabolism. Forty-one patients with MO were compared with age- and BMI-matched non-osteoporotic subjects after excluding overt systemic hypercortisolism (N = 41). Cortisol, cortisone and the respective tetrahydro-, 5α-tetrahydro- and total cortisol metabolites were analysed by GC-MS in 24 h urine. Apparent 11β-hydroxysteroid dehydrogenase (11β-HSD) enzyme activities, excretion of cortisol metabolites and calcium, and fractional urinary calcium excretion were assessed and related to BMD. Fractional and total urinary calcium excretion negatively correlated with BMD at all (P < 0.05) and at three of five (P < 0.05) measurement sites, respectively. While systemic cortisol was unchanged, apparent 11β-HSD enzyme activity in MO patients (P < 0.01) suggested increased intracellular cortisol availability. Total and fractional urinary calcium excretion was higher, with apparent 11β-HSD enzyme activities consistent with an enhanced intracellular cortisol availability (P < 0.05). Apparent 11β-HSD enzyme activities consistent with increased intracellular cortisol availability correlated with urinary calcium loss and reduced bone mineral density in MO. The changes in 11β-HSD activity were associated with both the fractional calcium excretion, suggesting altered renal calcium handling, and the absolute urinary calcium excretion. Both mechanisms could result in a marked bone calcium deficiency if insufficiently compensated for by intestinal calcium uptake.


Conchal Cartilage Graft for Correction of Bilateral Cleft Lip Nasal Deformities during Childhood.
Various methods for primary repair of bilateral cleft lip have been developed, but they often produce inadequate results, such as an upturned nose or a short columella. We perform primary lip repair with muscle reconstruction to correct depression of the nasal floor and inferoposterior displacement of the alar base. Then, open rhinoplasty to project the nasal tip is performed during childhood. This article describes the methods and results of open rhinoplasty for bilateral cleft lip patients. Open rhinoplasty with a modified forked flap is performed. The harvested conchal cartilage is grafted as a strut to strengthen and extend the septum. The lower lateral cartilages are sutured to the grafted cartilage and fixed in the correct position. Before skin closure, the tips of the 2 V flaps of the forked flap and the reverse V-flap between the forked flap are trimmed. Three trapezoidal flaps are sutured to the base of the columella. Thirty patients with bilateral cleft lip nasal deformities have undergone surgery. The operative results of 15 of 30 patients were evaluated photogrammetrically. The nose was refined and more projected. The nasolabial angle and the nasal tip projection were improved. The reformed configuration was well maintained for many years. Photogrammetric analysis demonstrated increases in both the nasal height-to-width ratio and the nostril height-to-width ratio and a decrease in the nasolabial angle. Open rhinoplasty during childhood using 3 trapezoidal flaps and conchal cartilage graft improves bilateral cleft lip nasal deformities effectively.


Ex vivo construction of rabbit corneal endothelial cell sheets on a porcine descemet membrane graft.
The aim of the present study was to investigate the feasibility of a new graft construction method using rabbit corneal endothelial cells (RCECs) and a porcine descemet membrane (DM) carrier. RCECs were isolated and the experimental group was treated with Y-27632, whereas the control group were cultured in medium without Y-27632. RCEC morphology was observed using an inverted microscope, and cell proliferation and apoptosis were detected by flow cytometry. To confirm the presence of RCECs, reverse transcription-quantitative PCR was used to detect gene expression levels of Na+-K+-ATPase, aquaporin 1, collagen α2 (IV), collagen α1 (VIII) and keratin-12. Histocompatibility testing was used to detect porcine DM antigenicity. A DM-RCEC graft was constructed, and morphology was observed using alizarin red-trypan blue and haematoxylin and eosin staining. Cell membrane potential was measured to evaluate the physical function of the DM-RCEC graft. Complex graft tension was measured using a modified tension detector and compared with fresh porcine DM-endothelium complex. In vitro-cultured RCECs formed a monolayer with a polygon morphology and cobblestone-like arrangement. In vitro-cultured RCECs exhibited typical RCEC characteristics before and after transplantation. The proliferation rates of the experimental and control groups were 62.68 and 34.50%, respectively (P<0.05); the apoptosis rates of the experimental and control groups were 8.99 and 35.68%, respectively (P<0.05). There was no antigenicity observed with the porcine DM. The action potential amplitude of the experimental and control groups was over -80 mV, reflecting normal RCEC physiological function. The tension measurements of the experimental and control groups were 20.0248±1.048 and 20.5013±0.657 g, respectively (P>0.05). Taken together, the results of the present study demonstrated that Y-27632 enhanced RCEC proliferation. In addition, the findings revealed the successful ex vivo construction of a RCEC sheet on a porcine DM graft.


Acetylcholinesterase inhibitors for electroconvulsive therapy-induced cognitive side effects: a systematic review.
Electroconvulsive therapy (ECT) is an effective treatment for severe late-life depression; however, ECT-induced cognitive side effects frequently occur. The cholinergic system is thought to play an important role in the pathogenesis. We systematically reviewed the evidence for acetylcholinesterase inhibitors (Ache-I) to prevent or reduce ECT-induced cognitive side effects. A systematic search was performed in Pubmed, EMBASE, PsychINFO, and the Cochrane database to identify clinical trials investigating the effect of Ache-I on ECT-induced cognitive side effects. Key search terms included all synonyms for ECT and Ache-I. Risk of bias assessment was conducted by using the Cochrane Collaboration's tool. Five clinical trials were eligible for inclusion. All studies focused on cognitive functioning as primary endpoint, but assessment of cognitive functioning varied widely in time point of assessment and in cognitive tests that were used. There was also great variety in study medication, route and time of administration and dosages, duration of drug administration, and ECT techniques. Finally, only two out of five studies were considered at low risk of bias. Despite the aforementioned shortcomings, without exception, all studies demonstrated significantly better cognitive performance in individuals treated with Ache-I. Despite large heterogeneity in studies, Ache-I appear to have beneficial effects on ECT-induced cognitive side effects, supporting an association with the cholinergic system in ECT-induced cognitive impairment. Methodological sound studies controlling for putative confounders are warranted. Copyright © 2017 John Wiley & Sons, Ltd.


Steady state models of stable isotopic distributions.
This study reviews common calculations and mathematical models used in stable isotopic studies. Some approximations are adopted to simplify the algebra for use in steady state models, with more rigorous mathematics outlined in an Appendix. Review shows that steady-state isotopic models are easy to construct, provide good approximations of system behavior, and are very helpful in evaluating isotopic cycling in many kinds of systems.


Transient effects in ice nucleation of a water drop impacting onto a cold substrate.
The impact of water drops onto a solid surface at subfreezing temperatures has been experimentally studied. Drop nucleation has been observed using a high-speed video system. The statistics of nucleation allows the estimation of the average number of nucleation sites per unit area of the wetted part of the substrate. We have discovered that the nucleation rate in the impacting drop is not constant. The observed significant increase of the nucleation rate at small times after impact t<50 ms can be explained by the generation of nanobubbles at early times of drop impact. These bubbles serve as additional nucleation sites and enhance the nucleation rate.


Stigma, COVID and Health Status Related Discrimination under Nigeria Law.
Stigmatisation of a person often leads to a demeaning treatment of the person by the public. There is a growing stigma about COVID-19 resulting in denials by some persons that members of their family died of COVID. This portends danger to public health as data and information-sharing are important ways of curbing challenges to public health. Stigmatisation may result in treating persons with health challenges like COVID in a discriminatory manner. This article reviews the remedies available to persons who have been discriminated against on the grounds of their health condition. It examines the constitutionality of the powers to restrict movement and the like, made to address the COVID-19 pandemic. It suggests how health stigmatisation can be curbed.


Reducing stress in the operatory.
Dentists can minimize the levels of physical and mental stress in dental offices by selecting suitable equipment and maintaining proper posture. The specific positions and allowable movements require a vigilant attitude on the part of dentists until these habits become established and are practiced routinely.


The Relation between the Rheological Properties of Gels and the Mechanical Properties of Their Corresponding Aerogels.
A series of low density, highly porous clay/poly(vinyl alcohol) composite aerogels, incorporating ammonium alginate, were fabricated via a convenient and eco-friendly freeze drying method. It is significant to understand rheological properties of precursor gels because they directly affect the form of aerogels and their processing behaviors. The introduction of ammonium alginate impacted the rheological properties of colloidal gels and improved the mechanical performance of the subject aerogels. The specific compositions and processing conditions applied to those colloidal gel systems brought about different aerogel morphologies, which in turn translated into the observed mechanical properties. The bridge between gel rheologies and aerogel structures are established in the present work.


[Surgical outcomes and prognostic factors of primary colorectal cancer with peritoneal dissemination].
We evaluated the surgical outcomes and prognostic factors of primary colorectal cancer with peritoneal dissemination. Between 1990 and 2012, a total of 81 cases of operated primary colorectal cancer with peritoneal dissemination were reviewed. According to the classification by the degree of peritoneal dissemination, the 3-year overall survival rate of patients with P1, P2, and P3 were 22%, 14%, and 16%, respectively. A significant difference was not observed between these 3 groups. According to the degree of surgical curability, the 1-year and 3-year overall survival rates of the patients with curability B were 75% and 30%, respectively. The overall survival rate of patients with curability B was higher than those of curability C (p< 0.01). Multivariate analysis showed that the curability of operation (p=0.03) and the existence of hepatic metastases (p=0.01) were significant prognostic factors affecting overall survival. The median relapse-free survival time of patients with curability B was 7.8 months. Nevertheless, long-term survivor cases existed in this group. These findings suggest that complete resection of the primary tumor and metastatic lesions is important to prolong survival term.


Functional neuroimaging indicators of successful executive control in the oldest old.
Attentional control, motor planning abilities, and executive cognitive functions (ECF) rapidly decline with age. In particular, older adults experience difficulty in manipulating selected motor responses in the presence of conflicting or distracting information. To examine age-related changes in the neural substrates of the attentional and motor planning components of ECF, we assessed the patterns of brain activation in 8 cognitively normal older adults (mean age 81.5) and 20 young individuals (mean age 23.0) while they responded to low and high loads of attentional demands of the Preparing to Overcome Prepotency (POP) task. In the POP task, the selection of one out of two possible motor responses in the presence of increasing attentional task loads determines the accuracy of the performance. Older individuals were slower than young adults (P < 0.001) but achieved a strikingly high accuracy similar to the young group (P = 0.2), regardless of the task load. Both groups showed a load-related fMRI signal increase in the anterior cingulate cortex (ACC), posterior parietal cortex (PPC: Brodmann areas 7 and 40), and dorsolateral prefrontal cortex (dLPFC: Brodmann areas 9, 45, and 46) bilaterally. Compared to young individuals, older adults had lower activation in dLPFC (Brodmann areas 9, 45, and 46: P = 0.007, P = 0.043, and P = 0.040) and Brodmann area 7, P = 0.002. Activation in Brodmann areas 40 and ACC was similar in the two groups (P > 0.05). Among older adults, the most successful performers were those who responded to increasing task loads with greater activation in PPC (Brodmann area 40), despite lower dLPFC activation. Older adults who are able to perform executive control tasks as well as young adults, also seem to implement speed-accuracy trade-off strategies which may rely on increased parietal activation.


Gene expression in X-irradiated human tumour cell lines expressing cisplatin resistance and altered DNA repair capacity.
Previous studies have indicated that excision repair genes, such as ERCC1, or early response genes, such as c-fos, may play a significant role in regulating cellular responses to cisplatin (CDDP) by mediating DNA synthesis and repair pathways. This present study aimed to determine whether altered gene expression mediated CDDP resistance expressed in two human tumour sublines following their in vitro exposure to fractionated X-irradiation, not to the drug itself. These sublines, designated SuSa/DXR10 and SKOV-3/DXR10, established respectively from a testicular teratoma cell line (SuSa) or an ovarian carcinoma cell line (SKOV-3), expressed stable 3.1- and 2-fold levels of CDDP resistance, as judged by clonogenic assay. Both sublines expressed c-fos, c-myc and thymidylate synthase (TS) RNA constitutively, but at comparable levels to their parental counterparts. Whilst the ovarian carcinoma cells inherently expressed markedly higher levels (30- to 50-fold) of the excision repair gene ERCC1 than the teratoma cells, only the teratoma DXR10 subline showed an increased level of expression of ERCC1 mRNA relative to their parental cells. Expression of the ERCC3/XPB gene encoding a repair helicase, however, was similar in all the lines tested. The results suggest that CDDP resistance may be mediated by different mechanisms in these DXR10 sublines from those previously identified in drug-selected CDDP-resistant human ovarian A2780/DDP cells.


Integrated stress response is critical for gemcitabine resistance in pancreatic ductal adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with marked chemoresistance and a 5-year survival rate of 7%. The integrated stress response (ISR) is a cytoprotective pathway initiated in response to exposure to various environmental stimuli. We used pancreatic cancer cells (PCCs) that are highly resistant to gemcitabine (Gem) and an orthotopic mouse model to investigate the role of the ISR in Gem chemoresistance. Gem induced eIF2 phosphorylation and downstream transcription factors ATF4 and CHOP in PCCs, and these effects occurred in an eIF2α-S51 phosphorylation-dependent manner as determined using PANC-1 cells, and wild type and S51 mutant mouse embryo fibroblasts. Blocking the ISR pathway in PCCs with the ISR inhibitor ISRIB or siRNA-mediated depletion of ATF4 resulted in enhanced Gem-mediated apoptosis. Polyribosomal profiling revealed that Gem caused repression of global translation and this effect was reversed by ISRIB or by expressing GADD34 to facilitate eIF2 dephosphorylation. Moreover, Gem promoted preferential mRNA translation as determined in a TK-ATF4 5'UTR-Luciferase reporter assay, and this effect was also reversed by ISRIB. RNA-seq analysis revealed that Gem upregulated eIF2 and Nrf2 pathways, and that ISRIB significantly inhibited these pathways. Gem also induced the expression of the antiapoptotic factors Nupr1, BEX2, and Bcl2a1, whereas ISRIB reduced their expression. In an orthotopic tumor model using PANC-1 cells, ISRIB facilitated Gem-mediated increases in PARP cleavage, which occurred in conjunction with decreased tumor size. These findings indicate that Gem chemoresistance is enhanced by activating multiple ISR-dependent pathways, including eIF2, Nrf2, Nupr1, BEX2, and Bcl2A1. It is suggested that targeting the ISR pathway may be an efficient mechanism for enhancing therapeutic responsiveness to Gem in PDAC.


[Assessment of effect of vaccination against pneumococcal infection in children with chronic renal failure and glomerulonephritis].
Clinical effect and immune response to vaccination with PNEUMO 23 vaccine was assessed in 18 children with chronic renal failure (CRF) and 40 children with different forms of glomerulonephritis (GN) aged 2 - 15 years. Control group was comprised by nonvaccinated patients (16 patients with CRF; 20 -with GN). Children from two groups were comparable on age and severity of disease's course. Local adverse reactions with duration not longer than 2 days were registered in 22% of vaccinees with CRF, and in 20% of vaccinees with GN. Mild and moderate systemic reactions were registered in 11% and 7.5% of recipients respectively. 1 month after vaccination significant 2.5 - 3.2-fold increase of antibodies concentration was detected in all groups irrespective from nosology and previous treatment. Two-fold increase of concentration of antibodies was observed in 64% and 61% of children with GN and CRF respectively. Clinical effect of vaccination appeared as 2.9-fold decrease of acute respiratory disease (ARD) incidence. Demand in antibacterial therapy decreased by 6.4-fold. Duration of ARD and course of antibacterial treatment decreased by 2.2 and 3 times respectively. Proportion of GN exacerbations related to infecvion decreased from 39% before vaccination to 8% after vaccination. In the control group this proportion did not change (50% and 45% respectively). Vaccine efficacy index was 2.13, coefficient of efficacy - 53.1%.


Progression of subclinical myocardial dysfunction in type 2 diabetes after 5 years despite improved glycemic control.
Patients with uncomplicated diabetes have reduced left ventricular long-axis function, related to poor glycemic control and increased conduit arterial stiffness, with increased radial function. It is unknown if improved control of risk factors can reverse these subclinical changes. We studied 27 patients with type 2 diabetes (18 men) 57 ± 1 months (mean ± SD) after an initial visit when they were compared with healthy age- and sex-matched controls. On both visits patients had detailed echocardiographic studies including tissue Doppler, noninvasive tests of conduit arterial function, and metabolic and lipid profiling. Mean age at this second review was 63.4 ± 8.1 years; 48% of patients received insulin. Mean HbA1c had decreased by 13% to 8 ± 1.6% and cholesterol by 17% to 4.3 ± 1.3 mmol/L (both, P < 0.01), but long-axis systolic and early diastolic myocardial velocities had also declined, by 13% and 20%, respectively (both, P < 0.001). Body mass index had increased by 4%, arterial pulse pressure by 17% (both P < 0.01), and carotid arterial stiffness by 49% (P < 0.01). Fractional shortening (by 21%, P < 0.001), radial systolic velocity (by 13%, P < 0.05), and ejection fraction (by 9% to 68 ± 7%, P < 0.01) had all declined. Reductions in longitudinal function were best predicted by its baseline measurements, duration of diabetes, fasting triglycerides, and arterial stiffness (epsilon index). Despite improved diabetic control, subclinical left ventricular dysfunction progressed over 5 years. Radial compensation was reversed. Prevention of subclinical myocardial dysfunction in diabetes might require more intensive control of net cardiovascular risk.


Screening of a Combinatorial Library of Organic Polymers for the Solid-Phase Extraction of Patulin from Apple Juice.
Patulin is a water-soluble mycotoxin produced by several species of fungi. Governmental bodies have placed it under scrutiny for its potential negative health effects, and maximum residue limits are fixed in specific food matrices to protect consumers' health. Confirmatory analysis of patulin in complex food matrices can be a difficult task, and sample clean-up treatments are frequently necessary before instrumental analyses. With the aim of simplifying the clean-up step, we prepared a 256-member combinatorial polymeric library based on 16 functional monomers, four cross-linkers and four different porogenic solvents. The library was screened for the binding towards patulin in different media (acetonitrile and citrate buffer at pH 3.2), with the goal of identifying polymer formulations with good binding properties towards the target compound. As a proof of concept, a methacrylic acid-co-pentaerithrytole tetraacrylate polymer prepared in chloroform was successfully used as a solid-phase extraction material for the clean-up and extraction of patulin from apple juice. Clean chromatographic patterns and acceptable recoveries were obtained for juice spiked with patulin at concentration levels of 25 (64 ± 12%), 50 (83 ± 5.6%) and 100 μg L-1 (76 ± 4.5%). The within-day and between-day reproducibility evaluated at a concentration level of 25 μg L-1 were 5.6 and 7.6%, respectively.


On outcomes and humility.
The competency movement in medical education asserts itself in every corner of students' experiences from matriculation through residency. Such a focus on making sure trainees achieve desired levels of skills, knowledge, and technique is highly desired by the patients they will be servicing, but educators' need to turn nearly every dimension of medical education into a competency is an ill-advised leap that transforms a complex educational mission into a bottom-line venture. This commentary provides a critical examination of the wholesale use of competency measures in academic medicine, using the concurrent articles by Murray-García and García about multiculturalism and by Kumagai about narrative medicine as thoughtful examples of educational efforts that turn away from this narrow orientation, focusing instead on the ongoing reflective processes and humility that mark the lifelong development of skilled, empathic physicianhood.


Lymphangioma of male exogenital organs.
Lymphangioma manifesting in the genitourinary tract is an uncommon disease. Cystic lymphangioma is a congenital lymphatic hamartoma known as lymphatic malformation. Herein we report 2 cases of lymphangioma of male exogenital organs. After complete excision of the tumor and subsequent follow-up for 6 months, both of them were free of recurrence. Ultrasonography and computed tomography scans are very useful in the differential diagnosis of this cystic disease.


Modular organization of cognitive systems masked by interhemispheric integration.
After resection of the corpus callosum, V.J., a left-handed woman with left-hemisphere dominance for spoken language, demonstrated a dissociation between spoken and written language. In the key experiment, words flashed to V.J.'s dominant left hemisphere were easily spoken out loud, but could not be written. However, when the words were flashed to her right hemisphere, she could not speak them out loud, but could write them with her left hand. This marked dissociation supports the view that spoken and written language output can be controlled by independent hemispheres, even though before her hemispheric disconnection, they appeared as inseparable cognitive entities.


Dendritic and Langerhans cells respond to Aβ peptides differently: implication for AD immunotherapy.
Both wild-type and mutated beta-amyloid (Aβ) peptides can elicit an immune response when delivered subcutaneously. However, only mutated forms of Aβ can sensitize dendritic cells when administered intravenously or intraperitoneally. To understand the role of mutation and delivery routes in creating immune responses, and the function of dendritic cells as therapeutic agents, we used fluorescent-conjugated WT Aβ1-40 (WT40) and artificially mutated Aβ1-40 (22W40) peptides to treat dendritic and Langerhans cells from young and/or old mice at different time points. The cell types were analyzed by flow cytometry and confocal microscopy to identify differences in function and antigen presentation, and Luminex and Western blots for cell activation and associated mechanisms. Our results demonstrated that the artificial mutant, 22W40, enhanced dendritic cell's phagocytosis and antigen presentation better than the WT40. Interestingly, Langerhans cells were more effective at early presentation. The artificial mutant 22W40 increased CD8α+ dendritic cells, CD8+ T-cells, and IFN-γ production when co-cultured with self-lymphocytes and dendritic cells from aged mice (30-month-old). Here, the 22W40 mutant peptide has been found to be potent enough to activate DCs, and that dendritic cell-based therapy may be a more effective treatment for age-related diseases, such as Alzheimer's disease (AD).


Preventing germinal matrix layer rupture and intraventricular hemorrhage.
The etiology of intraventricular hemorrhage (IVH) in extremely low birth weight preterm infants is multifactorial with circulatory instability and hemostasis being preeminent. This study sought to determine if the germinal matrix layer remained intact when platelets were above 200 × 10(9)/L, a near normal level, and fell below that when IVH occurred. This was a retrospective study of platelets and head ultrasounds (HUS) in infants 23-28 weeks gestation. Analyses were descriptive, one way analysis of variance, Pearson Chi-square tests, and t-tests. Platelet counts and HUS were linked in 114 infants during the first 3 days when 90% of IVHs occur. Mean platelet levels were >200 × 10(9)/L in 68% of infant 23-24 weeks gestation and 78% of those 25-26 weeks when there were no IVHs. These findings, if confirmed, suggest that improving hemostasis in high risk preterm infants by keeping platelet levels >200 × 10(9)/L may maintain the integrity of the germinal matrix layer and prevent IVHs.


Thymidylate synthase repeat polymorphisms and risk of neural tube defects in a population from the northern United Kingdom.
A 28-bp repeat polymorphism in the 5'UTR of the thymidylate synthase (TYMS) gene represents a candidate risk factor for neural tube defects (NTDs) due to involvement in folate-dependent homocysteine metabolism. Non-Hispanic, white, U.S. citizens carrying at least one 2x 28-bp repeat allele have recently been shown to be at a four-fold increased risk of spina bifida (SB). We investigated the association between this polymorphism and risk of NTD in families affected by NTDs and controls from the northern United Kingdom (UK). PCR was performed on genomic DNA extracted from blood or mouth swabs of family members affected by NTDs (mothers, fathers, and cases), and unaffected controls (mothers and infants) to determine the number of 28-bp repeat units within the promoter region of TYMS. Case-control and TDT analyses of the influence of TYMS genotype on risk of NTD, or NTD pregnancy, were conducted. Odds ratio (OR) analysis indicated that individuals carrying the 2x 28-bp repeat allele either in homozygous or heterozygous form, are not at increased risk of NTDs, or of having an NTD affected pregnancy. Control population allele frequencies are seen to be markedly different between the U.S. controls and those in this study. TYMS polymorphism appears to be not universally associated with NTD risk across Caucasian samples. The elevated risk of spina bifida in U.S. samples appears to be driven by an unusually low risk allele (2x 28 bp) frequency in control samples. Family based (TDT) testing of U.S. samples is therefore advocated.


Study of interleukin-6 in the spread of colorectal cancer: the diagnostic significance of IL-6.
We investigated the diagnostic significance of IL-6 for lymph node metastasis and/or hepatic metastasis from colorectal cancer in 65 patients and evaluated the contributions of 8 factors (IL-6, HGF, IL-1beta, TNF-alpha, TGF-beta1, ELAM-1, ICAM-1, VCAM-1) toward Dukes.s classification of 53 patients. We also examined IL-6 expression in tumor tissue. From the receiver operating characteristic (ROC) curve analysis, an optimal cutoff value of 5.8 pg/ml was determined to classify lymph node and/or hepatic metastasis, and that of 6.3 pg/ml was determined to classify hepatic metastasis. These values indicated sensitivities of 55.0% and 71.4%, and specifi cities of 100% and 88.6%, respectively. IL-6, HGF, and ELAM-1 were very useful for distinguishing among Dukes.s A/B group, C group, and D group. In all cases with high IL-6 values (more than 25.0 pg/ml), immunohistochemical staining was positive for IL-6 in the cytoplasm of cancer cells. IL-6 is strongly suspected to be involved in lymph node and/or hepatic metastasis by promoting it through HGF, and serum IL-6 value (pg/ml) would be useful diagnostically to estimate whether or not there is a high risk of lymph node and/or hepatic metastasis.