The leader protein of cardioviruses inhibits stress granule assembly.
Stress granules (SG) are cytoplasmic aggregates of stalled translation preinitiation complexes that form in cells exposed to various environmental stresses. Here, we show that stress granules assemble in cells infected with Theiler's murine encephalomyelitis virus (TMEV) mutants carrying alterations in the leader (L) protein, but not in cells infected with wild-type TMEV. Stress granules also formed in STAT1-deficient cells, suggesting that SG formation was not a consequence of increased type I interferon (IFN) production when cells were infected with the mutant virus. Ectopic expression of the wild-type L protein was sufficient to inhibit stress granule formation induced by sodium arsenite or thapsigargin treatment. In conclusion, TMEV infection induces stress granule assembly, but this process is inhibited by the L protein. Unlike poliovirus-induced stress granules, TMEV-induced stress granules did not contain the nuclear protein Sam68 but contained polypyrimidine tract binding protein (PTB), an internal ribosome entry site (IRES)-interacting protein. Moreover, G3BP was not degraded and was found in SG after TMEV infection, suggesting that SG content could be virus specific. Despite the colocalization of PTB with SG and the known interaction of PTB with viral RNA, in situ hybridization and immunofluorescence assays failed to detect viral RNA trapped in infection-induced SG. Recombinant Theiler's viruses expressing the L protein of Saffold virus 2 (SAFV-2), a closely related human theilovirus, or the L protein of mengovirus, an encephalomyocarditis virus (EMCV) strain, also inhibited infection-induced stress granule assembly, suggesting that stress granule antagonism is a common feature of cardiovirus L proteins.


In situ monitoring of functional activity of extracellular matrix stiffness-dependent multidrug resistance protein 1 using scanning electrochemical microscopy.
Extracellular matrix (ECM) stiffness affects the drug resistance behavior of cancer cells, while multidrug resistance protein 1 (MRP1) on the cell membrane confers treatment resistance via actively transporting drugs out of cancer cells. However, the relationship between ECM stiffness and MRP1 functional activity in cancer cells remains elusive, mainly due to the technical challenge of in situ monitoring. Herein, we engineered in vitro cancer cell models using breast cancer cells (MCF-7 and MDA-MB-231 cells) as the reprehensive cells on polyacrylamide (PA) gels with three stiffness, mimicking different developmental stages of cancer. We in situ characterized the functional activity of MRP1 and investigated the effect of ECM stiffness on MRP1 of cancer cells before and after vincristine treatment using scanning electrochemical microscopy (SECM) with ferrocenecarboxylic acid (FcCOOH) as the redox mediator and endogenous glutathione (GSH) as the indicator. The SECM results show that the functional activity of MRP1 is enhanced with increasing ECM stiffness, and the MRP1-mediated vincristine efflux activity of MCF-7 cells is more affected by ECM stiffness than that of MDA-MB-231 cells. This work, for the first time, applied SECM to in situ and quantitatively monitor the functional activity of MRP1 in cancer cells in different tumor mechanical microenvironments, which could help to elucidate the mechanism of matrix stiffness-dependent drug resistance behavior in cancer cells.


Treatment and Follow-up of Human Papillomavirus Infected Women in a Municipality in Southern Brazil.
This study aimed toanalyze the risk behavior for cervical cancer (CC) and the human papillomavirus (HPV) prevalence and resolution among women who received care through the private healthcare network of a municipality in southern Brazil. This descriptive and retrospective study was conducted with 25 women aged 20 to 59 years who received care through the private healthcare network and were treated at a specialty clinic in the period from January to December 2012 in a municipality in Northwest Parana, Southern Brazil. Data from medical records with cytological and HPV results were used. Following treatment, these women were followed-up and reassessed after 6 months. Data were statistically analyzed using the t-test and chi-squared test at a 5% significance level. The mean age of the studied women was 27.8±7.75 years old, and the majority were married, with paid employment and were non-smokers. The mean age at menarche was 13.0±0.50 years old, and the mean age at first intercourse was 17.5±1.78 years, with only 8.0% (2) initiating sexual activity at an age ≤15 years old. The majority had 1 to 2 children (60.0%), while 88.0% reported having had one sexual partner in their lifetime, and all the women were sexually active. A total of 68.0% used a hormonal contraceptive method. All the women had leukorrhea and pain and were infected by a single HPV type. Regarding the lesion grade, 80.0% showed high risk and 20.0% low risk. The most prevalent high-risk HPV strain was 16. These findings provide relevant information on HPV risk factors and infection, as well as the treatment and 6-month follow-up results, in economically and socially advantaged women with no traditional risk factors, corroborating previous reports that different risk factors may be described in different populations. Thus, this study reinforces the fact that even women without the traditional risk factors should undergo HPVmonitoring and assessment to determine the persistence of infection, promoting early diagnosis of the lesions presented and appropriate treatment to thus prevent the occurrence of CC.


BCL-2 expression in human colorectal adenomas and carcinomas.
As BCL-2 oncoprotein has been implicated as a survival factor in a number of tissues, we examined colorectal tumour specimens and cell lines for BCL-2 expression. BCL-2 protein was expressed in 19/22 adenocarcinomas and 12/13 adenomas. 6/9 carcinoma cell lines and 7/8 adenoma cell lines were also BCL-2 positive. BCL-2 expression was retained in metastases to the regional lymph nodes (3/3 specimens) and in the cell line SW620, derived from a lymph node metastasis. These studies suggest a role for BCL-2 in promoting cell survival of benign and malignant colorectal tumours and that BCL-2 deregulation may be a relatively early event in colorectal carcinogenesis. The retention of BCL-2 expression in the carcinomas and lymph node metastases may explain the resistance of colorectal tumours to chemotherapeutic treatment.


Diffuse interstitial brain edema in patients with end-stage renal disease undergoing hemodialysis: a tract-based spatial statistics study.
To investigate white matter (WM) alterations and their correlation with cognition function in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) using diffusion tensor imaging (DTI) with tract-based spatial statistics (TBSS) approach. This prospective HIPAA-complaint study was approved by our institutional review board. Eighty HD ESRD patients and 80 sex- and age-matched healthy controls were included. Neuropsychological (NP) tests and laboratory tests, including serum creatinine and urea, were performed. DTI data were processed to obtain fractional anisotropy (FA) and mean diffusivity (MD) maps with TBSS. FA and MD difference between the 2 groups were compared. We also explored the associations of FA values in WM regions of lower FA with ages, NP tests, disease, and dialysis durations, serum creatinine and urea levels of ESRD patients. Compared with controls, HD ESRD patients had lower FA value in the corpus callosum, bilateral corona radiate, posterior thalamic radiation, left superior longitudinal fasciculus, and right cingulum (P<0.05, FWE corrected). Almost all WM regions had increased MD in HD ESRD patients compared with controls (P<0.05, FWE corrected). In some regions with lower FA, FA values showed moderate correlations with ages, NP tests, and serum urea levels. There was no correlation between FA values and HD durations, disease durations, and serum creatinine levels of ESRD patients (all P>0.05). Diffuse interstitial brain edema and moderate WM integrity disruption occurring in HD ESRD patients, which correlated with cognitive dysfunction, and serum urea levels might be a risk factor for these WM changes.


Novel practical stereoselective synthesis of a bicyclic hydantoino-thiolactone as the key intermediate for production of (+)-biotin.
Bicyclic hydantoinothiolactone (1), as the key intermediate for production of (+)-biotin, has been efficiently and high-stereoselectively synthesized from the cheap starting material l-cystine via nine steps in 44% overall yield. In this new practical synthesis, there are two characteristic steps worthy of note. One step is TMSOTf-catalyzed efficient cyanation of (3S,7aR)-6-benzyl-5-oxo-3-phenyltetrahydro-1H,3H-imidazo[1,5-c]thiazol-7-yl acetate, the other step is DBU-catalyzed rapid isomerization of trans-isomer to cis-isomer of the bicyclic hydantoinothiolactone.


Cyclic di-GMP triggers the hypoxic adaptation of Mycobacterium bovis through a metabolic switching regulator ArgR.
During infection, intracellular pathogens inevitably face the pressure of hypoxia. Mycobacterium tuberculosis and Mycobacterium bovis represent two typical intracellular bacteria, but the signalling pathway of their adaptation to hypoxia remains unclear. Here, we report a new mechanism of the hypoxic adaptation in M. bovis driven by the second messenger molecule c-di-GMP. We found that c-di-GMP was significantly accumulated in bacterial cells under hypoxic stress and blocked the inhibitory activity of ArgR, an arginine metabolism gene cluster regulator, which increased arginine synthesis and slowed tricarboxylic acid cycle (TCA cycle) and aerobic respiration. Meanwhile, c-di-GMP relieved the self-inhibition of argR expression, and ArgR could interact with the nitrite metabolic gene regulator Cmr, promoting the positive regulation of Cmr and, thereafter, the nitrite respiration. Consistently, c-di-GMP significantly induced the expression of arginine and nitrite metabolism gene clusters and increased the mycobacterial survival ability under hypoxia. Therefore, we found a new function of the second messenger molecule c-di-GMP and characterized ArgR as a metabolic switching regulator that can coordinate the c-di-GMP signal to trigger hypoxic adaptation in mycobacteria. Our findings provide a potential new target for blocking the life cycle of M. tuberculosis infection.


Evaluating and reducing xerosis in competitive swimmers: an in vitro study and randomized controlled clinical trial.
Xerosis is a common problem with significant sequelae in competitive swimmers, and it results from transepidermal water loss. This study evaluates moisture barriers for reducing xerosis in competitive swimmers. An artificial skin model was used to evaluate five products. Models were measured for changes in thickness and weight over 7 days. The optimal barrier was tested in a randomized controlled trial (RCT) of 20 swimmers. Skin moisture content was serially measured. Skin micrographs were scored in a blinded fashion. The moisture barrier #1 treated skin model at day 7 maintained a mean thickness of 7.08 mm versus 2.38 mm for control (p = .0001). The mean weights of group 1 treated and control groups at day 7 were 40.1 and 8.65 g (p = .03). In the RCT, the group treated with moisture barrier #1 and the controls exhibited low moisture content and moderate xerosis scores at baseline. At week 3, moisture measurements for treated and control groups were 28.6% and 18.2% (p = .003). The mean xerosis scores for the treated and control groups were 8.5 and 12.9 (p = .0008). Artificial skin preservation varied for five commercially available moisture barriers. Moisture barrier application improved moisture content and reduced xerosis in competitive swimmers.


Phosphatidylinositol 3-kinase signaling pathway and inflammatory bowel disease: Current status and future prospects.
Inflammatory bowel disease (IBD) is a chronic life-limiting disease of gastrointestinal tract characterized by widespread enteric inflammation. IBD is a multifactorial disease, and different environmental, microbial, and immune-related factors give rise to the development of disease. Among several factors, the preponderance of pro-inflammatory T helper 17 cells over the anti-inflammatory regulatory T cells augments inflammation in the intestinal mucosa. Prevailing evidence accentuates that PI3K signaling pathway plays a central role in the pathophysiology of the condition by regulating the inflammatory process in the gut mucosa. By recognizing the implications of PI3K in the pathogenesis of IBD, agents that could modulate this pathway have recently been at the focus of research, yielding encouraging results mainly in the experimental IBD models. In this review, we have summarized the recent advances, which may hold the keys to identify novel therapeutic strategies for IBD.


Gastric acid hypersecretion in short bowel syndrome in infants: association with extent of resection and enteral feeding.
To determine the frequency of gastric acid hypersecretion in infants with chronic malabsorption due to short bowel syndrome, acid secretory function was determined in 23 infants with malabsorption 2-22 months following small bowel resection and in a control group of 14 chronically ill, age- and weight-matched infants who did not undergo bowel resection. The prevalence of basal acid hypersecretion (defined as acid output 2 SD above the mean for the control group) was 17% (4 of 23). Basal gastric acid hypersecretion was associated with two factors: massive small bowel resection and initiation of enteral feeding. Basal acid hypersecretion was present on the initial study in 3 of 7 infants with less than one-third of the small bowel remaining, but in only 1 of 16 with more than one-third intact (p less than 0.05). Hypergastrinemia was present in 3 of 6 infants following massive bowel resection, but in only 1 of 15 with more than one-third intact (p less than 0.05), but hypergastrinemia was not consistently associated with hypersecretion. In each of six previously unfed infants, a trial of enteral feeding resulted in increased basal and maximal acid output. Three infants developed basal acid hypersecretion during initiation of enteral feeding. There was no evidence of pentagastrin-stimulated maximal acid hypersecretion in any of the infants.


Enhanced catalytic activity through the tuning of micropore environment and supercritical CO2 processing: Al(porphyrin)-based porous organic polymers for the degradation of a nerve agent simulant.
An Al(porphyrin) functionalized with a large axial ligand was incorporated into a porous organic polymer (POP) using a cobalt-catalyzed acetylene trimerization strategy. Removal of the axial ligand afforded a microporous POP that is catalytically active in the methanolysis of a nerve agent simulant. Supercritical CO2 processing of the POP dramatically increased the pore size and volume, allowing for significantly higher catalytic activities.


Black South African students' use of counseling service.
This paper reports the demographic and summative annual data for presenting concerns of students seeking counseling at a Black South African university. Rankings of the major presenting concerns identified by the clients are presented.


[Clear and pale cells of the nipple epidermis: a critical study of their varieties].
The stratified squamous epithelium of the nipple-areola complex may contain pale cells including: Paget's disease cells (PDCs), Toker cells (TCs), and so-called clear cells (CCs). PDCs are atypical, commonly concentrated along the basal layer. They stain for EMA, CAM5.2, cytokeratin 7, and HER2/neu oncoprotein. TCs are bland cells with roundish and scant-chromatin nuclei. TCs are reactive for EMA, CAM5.2, and cytokeratin 7, but show negativity for HER2/ neu oncoprotein. The majority of cells that have been called epidermal CCs fit the features of pagetoid dyskeratosis, reactive for high molecular weight cytokeratin. Other CCs showing signet-ring morphology correspond to a fixation artefact.


Immunological aspects of uveitis in Bantu-speaking Negroes of South Africa.
Immunological studies in Bantu-speaking Negroes with uveitis consisted of a search of humoral antiuveal antibodies and immunologically competent cells. Using a tanned red cell hemagglutinating technique, no humoral antiuveal antibodies were detected in the blood of 87 patients nor in the aqueous of 6 patients. Lymphocyte blast transformation was negative in 80% of the patients tested and leukocyte migration inhibition positive in 75% of the patients tested. A discussion of these findings is presented.


Biomechanical comparison of intramedullary nail and plate osteosynthesis for extra-articular proximal tibial fractures with segmental bone defect.
Purpose: Proximal tibial fractures are common, but the current available internal fixation strategies remain debatable, especially for comminuted fractures. This study aimed to compare the biomechanical stability of three internal fixation strategies for extra-articular comminuted proximal tibial fractures. Methods: A total of 90 synthetic tibiae models of simulated proximal tibial fractures with segmental bone defects were randomly divided into three groups: Single lateral plating (LP), double plating (DP) and intramedullary nailing (IN). Based on the different number of fixed screws, the above three groups were further divided into nine subgroups and subjected to axial compression, cyclic loading and static torsional testing. Results: The subgroup of intramedullary nailing with five proximal interlocking screws showed the highest axial stiffness of 384.36 ± 35.00 N/mm. The LP group obtained the lowest axial stiffness performance with a value of 96.59 ± 16.14 N/mm. As expected, the DP group offered significantly greater biomechanical stability than the LP group, with mean static axial stiffness and mean torque increasing by approximately 200% and 50%, respectively. According to static torsional experiments, the maximum torque of the DP subgroup was 3,308.32 ± 286.21 N mm, which outperformed all other groups in terms of torsional characteristics. Conclusion: Utilizing more than four distal screws did not provide improved biomechanical stability in the LP or DP groups, while a substantial increase in the biomechanical stability of DP was obtained when an additional medial plate was used. For the intramedullary nailing group, increasing the number of proximal interlocking screws could significantly improve biomechanical stability, and the intramedullary nailing with three proximal interlocking screws had similar static and cyclic stiffness as the DP group. The intramedullary nailing with five proximal screws had better axial stability, whereas DP had better torsional stability.


Laboratory rearing of a hibernating animal, pocket mouse (Perognathus flavus).
Hibernating pocket mice (Perognathus flavus) were obtained from the Department of Veterinary Medicine, Hokkaido University, in September 1990, and attempted to rear them in National Institute of Neuroscience, NCNP. Rearing of pocket mice was possible under the general conditions used for rearing mice. As a result of random mating of 4 females to 2 males for breeding, gestation was achieved in only one pair of animals, and parturition under artificial rearing conditions was observed for the first time. The animal gave birth to 3 offspring that had no body hair. Their eyes were closed. Each of the offspring weighed about 1.0g. The mean body weight of the females was 6.5g and that of males 5.6g at 3 weeks. Weaning was possible at this age. Subsequently the animals grew rapidly; the body weight was almost equal to that of an adult animal (8.0g) at 5 weeks of age for the females and 7 weeks for the males. The gestation period was estimated to be 26 days. These findings indicate that pocket mice can be bred and reared under general laboratory conditions.


Single-incision versus conventional three-incision laparoscopic appendectomy: A meta-analysis of randomized controlled trials.
Conventional three-incision laparoscopic appendectomy (CTLA) is considered the new golden standard for the treatment of acute appendicitis. However, single-incision laparoscopic appendectomy (SILA) can further reduce the number of abdominal incisions and visible scars. Major databases were researched for randomized clinical trials (RCTs) comparing SILA and CTLA for acute appendicitis from January 1983 and to March 2015. The technical feasibility, effectiveness, and safety between SILA and CTLA were compared. Pooled odds ratios (ORs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects models. In total, 11 RCTs with 1489 patients were analyzed. The patients in the SILA group had a significantly shorter hospital duration (WMD: -0.63; 95% CI: -1.04, -0.21; P = 0.003) and return to activity (WMD: -2.91; 95% CI: -5.45, -0.37; P = 0.02) but experienced a longer operating time (WMD: 6.56; 95% CI: 3.55, 9.58; P < 0.0001) and higher rate of conversion (OR: 6.82; 95% CI: 3.14, 14.79; P < 0.00001). There were no differences between the two groups in visual analog pain scores, doses of analgesics, overall complication rates, wound infection, or cosmesis (all P > 0.05). SILA is a safer and more effective than CTLA in both pediatric and adult patients.


Detoxification of methylglyoxal by the glyoxalase system is required for glutathione availability and virulence activation in Listeria monocytogenes.
Listeria monocytogenes is a Gram-positive, food-borne pathogen that lives a biphasic lifestyle, cycling between the environment and as a facultative intracellular pathogen of mammals. Upon entry into host cells, L. monocytogenes upregulates expression of glutathione synthase (GshF) and its product, glutathione (GSH), which is an allosteric activator of the master virulence regulator PrfA. Although gshF mutants are highly attenuated for virulence in mice and form very small plaques in host cell monolayers, these virulence defects can be fully rescued by mutations that lock PrfA in its active conformation, referred to as PrfA*. While PrfA activation can be recapitulated in vitro by the addition of reducing agents, the precise biological cue(s) experienced by L. monocytogenes that lead to PrfA activation are not known. Here we performed a genetic screen to identify additional small-plaque mutants that were rescued by PrfA* and identified gloA, which encodes glyoxalase A, a component of a GSH-dependent methylglyoxal (MG) detoxification system. MG is a toxic byproduct of metabolism produced by both the host and pathogen, which if accumulated, causes DNA damage and protein glycation. As a facultative intracellular pathogen, L. monocytogenes must protect itself from MG produced by its own metabolic processes and that of its host. We report that gloA mutants grow normally in broth, are sensitive to exogenous MG and severely attenuated upon IV infection in mice, but are fully rescued for virulence in a PrfA* background. We demonstrate that transcriptional activation of gshF increased upon MG challenge in vitro, and while this resulted in higher levels of GSH for wild-type L. monocytogenes, the glyoxalase mutants had decreased levels of GSH, presumably due to the accumulation of the GSH-MG hemithioacetal adduct. These data suggest that MG acts as a host cue that leads to GSH production and activation of PrfA.


Deterministic Integration of Biological and Soft Materials onto 3D Microscale Cellular Frameworks.
Complex 3D organizations of materials represent ubiquitous structural motifs found in the most sophisticated forms of matter, the most notable of which are in life-sustaining hierarchical structures found in biology, but where simpler examples also exist as dense multilayered constructs in high-performance electronics. Each class of system evinces specific enabling forms of assembly to establish their functional organization at length scales not dissimilar to tissue-level constructs. This study describes materials and means of assembly that extend and join these disparate systems-schemes for the functional integration of soft and biological materials with synthetic 3D microscale, open frameworks that can leverage the most advanced forms of multilayer electronic technologies, including device-grade semiconductors such as monocrystalline silicon. Cellular migration behaviors, temporal dependencies of their growth, and contact guidance cues provided by the nonplanarity of these frameworks illustrate design criteria useful for their functional integration with living matter (e.g., NIH 3T3 fibroblast and primary rat dorsal root ganglion cell cultures).


Endothelin-1 upregulation in the kidney of uninephrectomized spontaneously hypertensive rats and its modification by the angiotensin-converting enzyme inhibitor quinapril.
Endothelin (ET-1) is a potent vasoconstrictor that plays an important role in the control of renal circulation and tubular function. The contribution of this peptide to the pathogenesis of systemic hypertension and renal failure remains largely undefined. In spontaneously hypertensive rats (SHR) uninephrectomized at 20 weeks of age (UNX-SHR) and followed until 45 weeks of age, we determined ET-1 gene expression in renal tissue by reverse transcription-polymerase chain reaction and its localization by in situ hybridization in paraffin-embedded kidney sections. Age-matched SHR and normotensive Wistar-Kyoto (WKY) rats were chosen as controls. At the end of the follow-up, UNX-SHR had high systolic blood pressure, intense proteinuria, mesangial expansion, focal and segmental glomerular sclerosis, and tubulointerstitial lesions. In relation to WKY and SHR, UNX-SHR exhibited an increase in ET-1 gene expression in renal cortex and medulla. By in situ hybridization and immunoperoxidase staining, an overexpression of ET-1 gene and protein were seen in mesangial and glomerular epithelial cells and in some proximal tubules and vessels. Angiotensin-converting enzyme (ACE) activity was significantly increased in the renal brush border. Since in mesangial cells, angiotensin II induces ET-1 synthesis, a group of UNX-SHR received the ACE inhibitor quinapril from the time of UNX. These animals had a decrease in blood pressure, proteinuria, and serum and brush border ACE activity and in the expression and synthesis of ET-1 in all renal areas. On the whole, these data show that UNX-SHR have an upregulation of ET-1 gene and protein in several structures of the kidney compared with SHR and WKY rats. Quinapril diminished ACE activity and ET-1 expression and synthesis coincidentally with an improvement in proteinuria and morphological lesions. The beneficial effects of ACE inhibitors may be due to the diminution of both angiotensin II and ET-1 generation.


Isotopes as host blood markers to measure blood intake by feeding ticks (Acari: Ixodidae).
We have modified an experimental technique in which two different isotopes (Cr51 and I125) were used simultaneously as blood markers for determining the amount of blood removed by feeding ticks. This method enables us to measure separately and directly the volumes of red blood cells and plasma in ticks and to calculate the ratio between the two parameters (concentrating ability). The concentration of red blood cells in nymphs of Amblyomma hebraeum Kock and Rhipicephalus appendiculatus Neumann and in females of these species plus in those of Hyalomma truncatum Kock were found to be twice the amount measured in the labeled blood of goats. Concentrations of plasma in the ticks were approximately two-thirds of that measured in samples taken directly from these same goats. Small nonsignificant differences between the ability of various tick species to concentrate red blood cells and dilute host plasma were found. The advantage of this method is compared with that of the colorimetric and gravimetric methods, and its potential use is discussed.


Induction of tumoricidal activity and alterations of growth by interleukin-2 and manipulation of protein kinase C and cytosolic calcium in childhood acute lymphocytic leukemia cells.
Signals from many receptor-ligand interactions are mediated by enhancement of phospholipid hydrolysis which generates metabolic intermediates stimulating protein kinase C (PKC) and elevating cellular calcium. Pharmacologic agents such as phorbol 12, 13-dibutyrate (PDBu) and ionomycin selectively stimulate PKC and elevate intracellular calcium to directly stimulate downstream mechanisms critical to cell growth and function. This study examines the effects of PDBu, ionomycin, and rIL-2 on childhood ALL blasts of early B lineage with respect to various aspects of cell activation, including DNA synthesis, induction of non-MHC restricted tumoricidal activity, and changes in morphology and phenotype. Five childhood ALL samples were tested. A marked heterogeneity was seen among the ALL samples with respect to in vitro growth following manipulation with PDBu, ionomycin, and/or rIL-2, whereas normal peripheral blood lymphocytes (PBL) were consistently stimulated to grow with the combination of PDBu and ionomycin. Growth responsiveness did not appear to correlate with morphologic or phenotypic classification of the leukemia samples. Four of the five leukemia samples developed substantial non-MHC restricted cytotoxicity to K562 (natural killer cell (NK) sensitive) and Daudi (NK resistant) targets in response to rIL-2. This functional cytotoxic response correlated with morphologic changes in the cells and the appearance of granules. Phenotypic analyses of the ALL samples at the time of their peak cytotoxic function were consistent with the fresh ALL phenotype and showed no major change in cell populations. Three of the five ALL samples also retained rIL-2 induced cytotoxic capabilities when exposed simultaneously to the combination of PDBu and ionomycin, whereas rIL-2 induced tumoricidal activity in normal PBL and bone marrow cultures was inhibited by these reagents. These data show that morphologically and phenotypically similar ALL blasts have heterogeneous proliferative responses to the PKC and calcium modulators PDBu and ionomycin, as well as to rIL-2. Cytotoxic responses are also different from those of normal PBL and bone marrow cells with respect to kinetics and responsiveness to inducing agents. Thus current morphologic and phenotypic classifications of ALL may not adequately reflect the heterogeneity of this disorder as described here.


Interdependent Diversities: Reflections on the Community-Diversity Dialectic.
This commentary reflects on the Community-Diversity Dialectic, summarizing its development and reviewing its impact on community psychology research and practice. Two contemporary examples are presented to illustrate both the possibilities of and challenges to bridging the gap between sense of community and diversity: the rise of the so-called "alt-right" on the one hand, and the popularity of Pokémon Go on the other. The article concludes with a brief discussion of Kurt Lewin's contributions to group dynamics theory, recommending that an emphasis on our interdependent fates and goals is paramount to reconciling the tensions between sense of community and diversity that persist in an increasingly complex multicultural world.


Cordyceps cardinalis sp. nov., a new species of Cordyceps with an east Asian-eastern North American distribution.
Cordyceps cardinalis, a pathogen of lepidopteran larva, is described as a new species from the southern Appalachian Mountains of the eastern United States and from southeastern Japan. It is macroscopically similar to both C. militaris and C. pseudomilitaris, however, microscopic, cultural and molecular evidence support it being a phylogenetically distinct species. Cordyceps cardinalis is most similar to C. pseudomilitaris in the microscopic characters of non-disarticulating ascospore morphology and its host affinity for lepidopteran larvae, which contrast with the characters of C. militaris. Aspects of morphology, host association, phylogeny and biogeography are discussed.


[Changes in the bioelectrical activity of the biceps femoral muscles in the diplegic form of infantile cerebral palsy].
The author performed an EMG study of the biceps femoris muscle and their proximal and distal parts in 15 normals and 42 patients with diplegic forms of infantile cerebral palsy. In patients with infantile cerebral palsy there were significant coordinational disturbances in the bioelectric activity of the muscles of the thigh during walking and an orthostatic position. These changes had characteristic traits depending upon the influence of preserved primitive tonic reflexes.


Photoelectron spectroscopy of hydrated hexafluorobenzene anions.
We present a synergetic experimental/theoretical study of hydrated hexafluorobenzene anions. Experimentally, we measured the anion photoelectron spectra of the anions, C6F6(-)(H2O)n (n=0-2). The spectra show broad peaks, which shift to successively higher electron binding energies with the addition of each water molecule to the hexafluorobenzene anion. Complementing these results, we also conducted density functional calculations which link adiabatic electron affinities to the optimized geometric structures of the negatively charged species and their neutral counterparts. Neutral hexafluorobenzene-water complexes are not thought to be hydrogen bonded. In the case of C6F6(-)(H2O)1, however, its water molecule was found to lie in the plane of the hexafluorobenzene anion, bound by two O-H...F ionic hydrogen bonds. Whereas in the case of C6F6(-)(H2O)2, both water molecules also lie in the plane of and are hydrogen bonded to the hexafluorobenzene anion but on opposite ends. This study and that of Schneider et al. [J. Chem. Phys. 127, 114311 (2007), preceding paper] are in agreement regarding the geometry of C6F6(-)(H2O)1.


Flows of living polymer fluids.
We report on the recent progress made on flows of living polymer fluids. Such fluids have been model systems for rheological research for more than twenty years and they continue to be fascinating. Like most if not all soft matter systems, living polymers under flow show a strong feedback between the structure of the fluid and that of the flow, the first influencing the second and vice versa. In our opinion, such interplay between microscopic kinetics and macroscopic kinematics has historically been mostly understood from a "structural perspective", in the tradition of physical chemistry. Nevertheless, in recent years, a more "hydrodynamical perspective" has emerged by making fruitful analogies with elastic and inertio-elastic instabilities known in solutions of regular polymers. We also underline how this new perspective constrains theoretical modelling and calls for the use of new tools of investigation.


[Main syndromes revealed in a consultation specially focusing on memory].
This paper reports our 2-year experience in a memory clinic practice at a University Hospital. During these 2 years, 128 patients with memory complaints were evaluated by a neurologist, a psychiatrist, a geriatrist and a neuropsychologist using a standardized test battery; only 58 of these patients actually presented with objective memory deficits. These memory impairments were mainly observed in patients with neurologic disorders (principally dementia) and in patients with psychiatric disorders (principally depression, major anxiety and psychiatric diseases with troubles of personality). The aim of this memory clinic is to identify the origin of memory disorders, provide a pharmacological treatment when required, propose appropriate assessment and follow up, and diagnose early symptoms of dementia.


Optimization of Bomaplex Red CR-L dye removal from aqueous solution by electrocoagulation using aluminum electrodes.
In this paper, Taguchi method was applied to determine the optimum dye removal from aqueous solution by electrocoagulation using aluminum electrodes. An orthogonal array (OA(16)) experimental design that allows to investigate the simultaneous variations of five parameters (initial dye concentration, initial pH of the solution, supporting electrolyte concentration, supporting electrolyte type and current density) having four levels was employed to evaluate the effects of experimental parameters. Performance measure analysis was followed by performing a variance analysis, in order to determine the optimum levels and relative magnitude of the effect of parameters. Because the desired characteristic for response has been maximum decolorization, Taguchi's 'the larger the better' performance formula was used. While the optimum conditions were found to be initial dye concentration of 100 mg/L, initial pH of the solution of 3, supporting electrolyte concentration of 0.0 mM, supporting electrolyte type of CaCl(2) and current density of 0.50 mA/cm(2). Under these optimum conditions, energy consumption is 0.607 kWh/kg dye, when the system evaluated also based on the energy consumptions it can be said that optimum conditions should be modified as follows: supporting electrolyte concentration of 2.5 mM; supporting electrolyte type NaCl, for 100 mg/L initial dye concentration; initial pH of the solution of 3; current density of 0.50 mA/cm(2).


Diagnosis of zygomaticus muscle paralysis using needle electromyography with ultrasonography.
A 22-year-old woman visited our clinic with a history of radiofrequency volumetric reduction for bilateral masseter muscles at a local medical clinic. Six days after the radiofrequency procedure, she noticed a facial asymmetry during smiling. Physical examination revealed immobility of the mouth drawing upward and laterally on the left. Routine nerve conduction studies and needle electromyography (EMG) in facial muscles did not suggest electrodiagnostic abnormalities. We assumed that the cause of facial asymmetry could be due to an injury of zygomaticus muscles, however, since defining the muscles through surface anatomy was difficult and it was not possible to identify the muscles with conventional electromyographic methods. Sono-guided needle EMG for zygomaticus muscle revealed spontaneous activities at rest and small amplitude motor unit potentials with reduced recruitment patterns on volition. Sono-guided needle EMG may be an optimal approach in focal facial nerve branch injury for the specific localization of the injury lesion.


Coexistence of Two Different Thyroid Malignancies: A Collision Phenomenon.
The term "collision tumor" is described as the coexistence of two or more histologically distinct neoplastic morphologies separated by normal tissue in the same organ. Simultaneous papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) of the same thyroid lobe is a very rare pathology. Herein, we report a case of PTC and FTC of the same thyroid lobe. A 79-year-old man was evaluated at our hospital for the presence of left hip pain of two-month duration after sustaining a physical trauma to the left side of his body three days prior to admission. X-ray imaging of the left femur revealed a large lytic bony lesion at the proximal end of left femur. Biopsy of the bone lesion was suggestive of FTC. Computed tomography (CT) of the neck revealed an enlarged thyroid with a cystic lesion in the left lobe of the thyroid gland. Total thyroidectomy was performed. Histopathology revealed two separate primary malignancies of PTC and FTC. Genetic studies for RAS gene mutation were negative. He was initiated on suppressive doses of levothyroxine following thyroidectomy. Three months after surgery, thyrotropin alfa stimulated 204.5 mCi I-131 was administered. At seven months of follow-up, the thyroglobulin level was in the lower end of the normal range and anti-thyroglobulin antibody (anti Tg) remained negative (< 1.0 IU/mL). He was doing well and reported no symptoms. For each type of well-differentiated thyroid cancers, several genes have been identified. However, thus far, no specific gene mutation responsible for the pathogenesis of the different tumor types has been described. Management of thyroid collision tumor is usually complex due to the presence of different pathology in the tumor tissues and given the fact that literature on this condition is limited. Typically, the treatment needs to be individualized. Our report brings up a concept that the occurrence is a rare phenomenon of simultaneous mutation of different genes that could give rise to different thyroidal neoplasms.


Ng-MIP, a surface-exposed lipoprotein of Neisseria gonorrhoeae, has a peptidyl-prolyl cis/trans isomerase (PPIase) activity and is involved in persistence in macrophages.
Macrophage infectivity potentiators (MIPs) are a family of surface-exposed virulence factors of intracellular microorganisms such as Legionella, Chlamydia and Trypanosoma. These proteins display peptidyl-prolyl cis/trans isomerase (PPIase) activity that is inhibited by immunosuppressants FK506 and rapamycin. Here we describe the identification and characterization in Neisseria gonorrhoeae of Ng-MIP, a surface-exposed lipoprotein with high homology to MIPs. The protein is an homodimer with rapamycin-inhibited PPIase activity confirming that it is a functional member of the MIP family. A knock-out strain, generated by deletion of the mip gene in N. gonorrhoeae F62 strain, was evaluated for its role in infection of mouse and human macrophages. We show that Ng-MIP promotes the intracellular survival of N. gonorrhoeae in macrophages, highlighting a possible role of this protein in promoting the persistence of gonococcal infection.


[Evaluation of the capacity of work using upper limbs after radical latero-cervical surgery].
Evaluation of arm work capacity after radical neck surgery. The aim of this paper is to describe an approach for the assessment of work capacity in patients who underwent radical neck surgery, including those treated with radiation therapy. Nine male patients, who underwent radical neck surgery 2 months before being referred to our Unit, participated in the study. In addition to manual muscle strength test, we performed the following functional evaluations: 0-100 Constant scale for shoulder function; maximal shoulder strength in adduction/abduction and intrarotation/extrarotation; instrumental. We measured maximal isokinetic strength (10 repetitions) with a computerized dynamometer (Lido WorkSET) set at 100 degrees/sec. During the rehabilitation phase, the patients' mechanical parameters, the perception of effort, pain or discomfort, and the range of movement were monitored while performing daily/occupational task individually chosen on the simulator (Lido WorkSET) under isotonic conditions. On this basis, patients were encouraged to return to levels of daily physical activities compatible with the individual tolerable work load. The second evaluation at 2 month confirmed that the integrated rehabilitation protocol successfully increased patients' capacities and "trust" in their physical capacity. According to the literature, the use of isokinetic and isotonic exercise programs appears to decrease shoulder rehabilitation time. In our experience an excellent compliance has been noted. One of the advantages of the method proposed is to provide quantitative reports of the functional capacity and therefore to facilitate return-to-work of patients who underwent radical neck surgery.


The removal efficiency of lead from contaminated soil: modeling of cations and anions migration during the electrokinetic treatment.
The effect of the presence of minerals in natural soil polluted with lead (II) was investigated to verify the efficiency of the electrokinetic remediation method. Natural soil "Sebkha of Oran" containing high calcite minerals and characterized by high salinity was used in experimental studies. This study investigates the effects of alkaline soil pH conditions on the transport and removal of lead by the electrokinetic treatment. XRD analyses were performed on the soil sample before and after electrokinetic treatment to determine any changes in mineral phases. Mathematical models using experimental data are developed to describe the mobility and diffusion coefficient of lead ions through the soil. Mathematical models were generated based on the physicochemical parameters characterizing the movement of cations and anions.


Cardiorenal syndromes: pathophysiology to prevention.
There is a strong association between both acute and chronic dysfunction of the heart and kidneys with respect to morbidity and mortality. The complex interrelationships of longitudinal changes in both organ systems have been difficult to describe and fully understand due to a lack of categorization of the common clinical scenarios where these phenomena are encountered. Thus, cardiorenal syndromes (CRSs) have been subdivided into five syndromes which represent clinical vignettes in which both the heart and the kidney are involved in bidirectional injury and dysfunction via a final common pathway of cell-to-cell death and accelerated apoptosis mediated by oxidative stress. Types 1 and 2 involve acute and chronic cardiovascular disease (CVD) scenarios leading to acute kidney injury (AKI) or accelerated chronic kidney disease (CKD). Types 3 and 4 describe AKI and CKD, respectively, leading primarily to heart failure, although it is possible that acute coronary syndromes, stroke, and arrhythmias could be CVD outcomes in these forms of CRS. Finally, CRSs type 5 describe a systemic insult to both heart and the kidneys, such as sepsis, where both organs are injured simultaneously in persons with previously normal heart and kidney function at baseline. Both blood and urine biomarkers, including the assessment of catalytic iron, a critical element to the generation of oxygen-free radicals and oxidative stress, are reviewed in this paper.


Extracellular matrix synthesis and ultrastructural changes of degenerative disc cells transfected by Ad/CMV-hTGF-beta 1.
To determine whether the synthesis of proteoglycan, collagen and associated ultrastructure are related to the adenovirus-mediated gene transferred to adult degenerative cells. Adenovirus/cytomegalovirus human transforming growth factor-beta 1 (Ad/CMV-hTGF-beta 1) was used to transfect degenerative cells. Antonopulos method, Miamine method and transmission electron microscopy were conducted to study the synthesis of proteoglycan, collagen, and ultrastructure, respectively. Cell cultures were established from the nucleus pulpous and annulus fibrosus tissues, which were taken from surgery. Nucleus pulpous and annulus fibrosus cells were efficiently transduced by the adenoviral vector carrying hTGF-beta 1 gene. The synthesis of proteoglycan and collagen increased compared with the control group (P < 0.05). The metabolism of cells was slightly improved. No significant toxic effects were found. Expression of hTGF-beta 1 gene is efficient to accelerates proteoglycan synthesis and thus accelerates the improvement of collagen. The function and structure of degenerative cells are improved. Ad/CMV-hTGF-beta 1 may be suitable for treating disc degeneration.


[Management of ovarian cysts].
Ovarian cysts occur frequently in women of reproductive age. These are usually functional cysts which resolve spontaneously and whose evolution can be followed with ultrasound. Non-functional cysts have diverse histologic origins. The most common are serous and mucinous cystadenomas which arise from the epithelial wall of the ovary, endometriomas which arise in the setting of pelvic endometriosis, and dermoid cysts which arise from the germinal cells of the ovary. Endovaginal ultrasound with Doppler enhancement is the best imaging technique to establish the nature of cysts and to distinguish cysts suspicious for malignancy which require more invasive investigation. Pelvic laparoscopy is the surgical approach of choice for the treatment of non-functional benign ovarian cysts. Conservative treatment to shell out the cyst and preserve functional ovarian tissue should be reserved for women desirous of future pregnancies. The risk of ovarian cancer remains a major preoccupation of the surgeon. Where malignancy is suspected, laparoscopy is contraindicated and a median laparotomy is appropriate for radical extirpative surgery. This article describes the diagnostic techniques which allow a laparoscopic approach to presumably benign cysts and discusses surgical techniques specifically adapted to their different histologic nature of ovarian cysts.


A self-sustaining high-strength wastewater treatment system using solar-bio-hybrid power generation.
This study focuses on system analysis of a self-sustaining high-strength wastewater treatment concept combining solar technologies, anaerobic digestion, and aerobic treatment to reclaim water. A solar bio-hybrid power generation unit was adopted to power the wastewater treatment. Concentrated solar power (CSP) and photovoltaics (PV) were combined with biogas energy from anaerobic digestion. Biogas is also used to store the extra energy generated by the hybrid power unit and ensure stable and continuous wastewater treatment. It was determined from the energy balance analysis that the PV-bio hybrid power unit is the preferred energy unit to realize the self-sustaining high-strength wastewater treatment. With short-term solar energy storage, the PV-bio-hybrid power unit in Phoenix, AZ requires solar collection area (4032m2) and biogas storage (35m3), while the same unit in Lansing, MI needs bigger solar collection area and biogas storage (5821m2 and 105m3, respectively) due to the cold climate.


Molecular Detection of Clumping factor A gene and Antibiotic Susceptibility Evaluation of Staphylococcus Aureus Isolated from Urinary Tract Infections.
The present study aimed to isolate and diagnose Staphylococcus Aureus (S. aureus) from clinical specimens of patients infected with urinary tract infections and evaluate the bacteria's resistance to antimicrobial agents. Additionally, it attempted to study the existence of the clumping factor A (clfA) gene. This study took place in Najaf province, Iraq, from December 2020 to April 2021 and included 40 clinical specimens taken from urine. In order to make an initial diagnosis of S. aureus isolates, microscopic evaluation was used in conjunction with culture and biochemical features. The automatic final diagnostic provided by the VITEK-2 compact system (bioMérieux, France) was utilized, which had a significant advantage. The results showed that 27 (67.5%) isolates gave positive results for S. aureus, 2 (5%) isolates for Streptococcus pyogenes, 6 (15%) isolates for Lactobacillus, and 5 (12.5%) for Escherichia coli. Antibiotic sensitivity test was conducted by disk diffusion methods, in which the isolates showed high resistance to ceftriaxone, as well as erythromycin, and they showed sensitivity to vancomycin, gentamicin, amikacin, and ciprofloxacin. The findings led to a concluding remark that all of the S. aureus isolates were clfA gene positive.


Diagnostic value of minor salivary glands biopsy for the detection of Lewy pathology.
The recent demonstration of the presence of Lewy pathology in the submandibular glands of Parkinson's disease (PD) patients prompted us to evaluate the diagnostic performance of minor salivary gland biopsy for PD. Minor salivary glands were examined for Lewy pathology using phosphorylated alpha-synuclein antibody in 16 patients with clinically diagnosed PD and 11 control subjects with other neurological disorders. Abnormal accumulation of alpha-synuclein was found in 3 out of 16 PD patients. Two control subjects exhibited weak phosphorylated alpha-synuclein immunoreactivity. Our results do not support the use of minor salivary glands biopsy for the detection of Lewy pathology in living subjects.


Viral antigens act as helper determinants for antibody responses to cell surface antigens.
Thy-1 alloantigens on murine thymus cells are weak immunogens in vivo for PFC responses in the absence of other antigenic disparities between the donor and recipient. Our previous work showed that non-H-2 alloantigens acted as helper determinants to augment anti-Thy-1 PFC responses. In this report we demonstrate that strong helper antigens are also produced by infection of donor thymus cells with viruses such as HSV-1, NDV, or vaccinia. This helper effect (as much as 30-fold) for a cellular antigen, requires linked recognition (expression of Thy-1 and virus in the same cell membrane), is T-dependent, antigen- (virus) specific, and is Thy-1-specific. The recognition of the viral helper sites is not restricted by the MHC genotype of the thymus cell donor, indicating that host reprocessing of antigen occurs. These are the first results that show that adventitious antigens may function as helper determinants for antibody responses to native membrane antigens and may be the mechanism that initiates several forms of acute post-viral autoimmune disease.


Cartilage fibrillation on the lateral tibial plateau in Liverpool necropsies.
A study has been made of the state at necropsy of the hyaline articular cartilage of the left tibial plateaux, with particular reference to the lateral plateau, in 47 adult white Europeans (24 men; 23 women) aged 21-88 years. The surface morphology and topographical distribution of the lesions is described for the bare area of the lateral plateau and its meniscus-covered segments, and quantitative point-counting data are presented for the amount, according to age, of overt fibrillation on the bare area. A variety of cartilage lesions was encountered: macroscopically apparent ' parallel linear' minimal fibrillation; other patterns of minimal fibrillation; 'ravines'; overt fibrillation; localized incomplete defects of the cartilage; and full-thickness cartilage loss with bone exposure. Sites of superficial fraying and splitting of the hyaline articular cartilage are a normal finding on adult human tibial plateaux. Especially in younger adults, such sites are often accompanied by large areas of cartilage surface which are still intact. On the lateral plateau, the bare area and the meniscus-covered posterior segment are more susceptible to overt fibrillation than are the meniscus-covered lateral and anterior segments. In contrast to the findings in other synovial joints, the peripheral rim of the upper tibial cartilage sheet is not particularly susceptible to overt fibrillation. Tangential extension of the changes on the lateral plateau leads to widespread involvement of the bare area and the meniscus-covered posterior segment in older subjects. However, vertical progression of the changes, sufficient to give full-thickness cartilage loss with tibio-femoral bone exposure, was seen in only a minority of persons aged over 80 years.


Scaffold protein RACK1A positively regulates leaf senescence by coordinating the EIN3-miR164-ORE1 transcriptional cascade in Arabidopsis.
Plants have adopted versatile scaffold proteins to facilitate the crosstalk between multiple signaling pathways. Leaf senescence is a well-programmed developmental stage that is coordinated by various external and internal signals. However, the functions of plant scaffold proteins in response to senescence signals are not well understood. Here, we report that the scaffold protein RACK1A (RECEPTOR FOR ACTIVATED C KINASE 1A) participates in leaf senescence mediated by ethylene signaling via the coordination of the EIN3-miR164-ORE1 transcriptional regulatory cascade. RACK1A is a novel positive regulator of ethylene-mediated leaf senescence. The rack1a mutant exhibits delayed leaf senescence, while transgenic lines overexpressing RACK1A display early leaf senescence. Moreover, RACK1A promotes EIN3 (ETHYLENE INSENSITIVE 3) protein accumulation, and directly interacts with EIN3 to enhance its DNA-binding activity. Together, they then associate with the miR164 promoter to inhibit its transcription, leading to the release of the inhibition on downstream ORE1 (ORESARA 1) transcription and the promotion of leaf senescence. This study reveals a mechanistic framework by which RACK1A promotes leaf senescence via the EIN3-miR164-ORE1 transcriptional cascade, and provides a paradigm for how scaffold proteins finely tune phytohormone signaling to control plant development.


Complement-activating donor-specific anti-HLA antibodies in solid organ transplantation: systematic review, meta-analysis, and critical appraisal.
Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ transplant outcomes. However, a critical appraisal of these studies and a demonstration of the prognostic value of complement-activating status over anti-HLA DSA mean fluorescence intensity (MFI) level are lacking. We conducted a systematic review, meta-analysis and critical appraisal evaluating the role of complement-activating anti-HLA DSAs on allograft outcomes in different solid organ transplants. We included studies through Medline, Cochrane, Scopus, and Embase since inception of databases till May 05, 2023. We evaluated allograft loss as the primary outcome, and allograft rejection as the secondary outcome. We used the Newcastle-Ottawa Scale and funnel plots to assess risk of bias and used bias adjustment methods when appropriate. We performed multiple subgroup analyses to account for sources of heterogeneity and studied the added value of complement assays over anti-HLA DSA MFI level. In total, 52 studies were included in the final meta-analysis (11,035 patients). Complement-activating anti-HLA DSAs were associated with an increased risk of allograft loss (HR 2.77; 95% CI 2.33-3.29, p<0.001; I²=46.2%), and allograft rejection (HR 4.98; 95% CI 2.96-8.36, p<0.01; I²=70.9%). These results remained significant after adjustment for potential sources of bias and across multiple subgroup analyses. After adjusting on pan-IgG anti-HLA DSA defined by the MFI levels, complement-activating anti-HLA DSAs were significantly and independently associated with an increased risk of allograft loss. We demonstrated in this systematic review, meta-analysis and critical appraisal the significant deleterious impact and the independent prognostic value of circulating complement-activating anti-HLA DSAs on solid organ transplant risk of allograft loss and rejection.


Metastasis of parotid adenocarcinoma to the external auditory canal.
Metastatic carcinoma of the external auditory canal (EAC) is extremely rare. Herein, we report the first case of a patient with metastasis of parotid adenocarcinoma to the EAC. Clinicians should include it in the differential diagnosis of tumors of the EAC. In patients with parotid carcinoma, a physical examination of the entire head and neck, including the EAC, should be performed before surgery.


Curcumin induces cell cycle arrest and apoptosis of prostate cancer cells by regulating the expression of IkappaBalpha, c-Jun and androgen receptor.
Curcumin possesses chemopreventive properties against several types of cancer, but the molecular mechanisms by which it induces apoptosis of cancer cells and inhibits cancer cell proliferation are not clearly understood. To evaluate the antitumor activity of curcumin for prostate cancer, we used an androgen dependent LNCaP prostate cancer cell line and an androgen independent PC-3 prostate cancer cell line as experimental models. We treated these cells with curcumin and then evaluated the effects of curcumin on cell cycle profiling and apoptosis, as well as the activation of NF-kaapaB and c-jun in these cells. The results showed that the ratios of apoptosis in LNCaP and PC-3 cells were significantly elevated in a dose dependent manner after exposure to curcumin. In addition, curcumin induces the G2/M cell cycle arrest of LNCaP and PC-3 cells in a dose dependent manner. Mechanistically, we found that curcumin upregulated the protein level of NF-kappaB inhibitor IkappaBalpha and downregulated protein levels of c-Jun and AR. These data suggest that curcumin is a promising agent for the treatment of both androgen-dependent and androgen-independent prostate cancer.


Clinical development of P glycoprotein modulators in oncology.
The last two decades have witnessed dramatic advances into the mechanisms of drug resistance in cancer. The identification of P glycoprotein (Pgp) as a specific mechanism led to the initial hope and expectation that it would be possible to modulate this and increase sensitivity to drug therapy. Clinical trials using first- and second-generation Pgp modulators did establish proof of principle that in some settings, clinical drug resistance could be overcome with the addition of a Pgp modulator-for example, clinical resistance to paclitaxel, a Pgp substrate, in women with ovarian cancer was shown to be overcome in approximately 20% with the addition of PSC 833, a highly effective Pgp modulator. However, evolutionary and adaptive redundancy in resistance mechanisms have tempered clinical results, even with very effective second- and third-generation modulators. The lessons from oncology establish sound methodology for the evaluation of Pgp modulators for safety, tolerability and efficacy in Phase I, II and III clinical trials. This review will focus on some of the early-phase clinical trials with earlier and newer Pgp modulators, either as single agents or in combination with chemotherapy.


Transdermal testosterone may improve ovarian response to gonadotrophins in low-responder IVF patients: a randomized, clinical trial.
Studies in macaques have indicated that androgens have some synergistic effects with FSH on folliculogenesis. This study investigated the usefulness of pretreatment with transdermal testosterone in low-responder IVF patients. Randomized clinical trial including 62 infertile women who had a background of the first IVF treatment cycle cancelled because of poor follicular response. Patients were randomized in two treatment groups in their second IVF attempt. In patients in Group 1 (n = 31), transdermal application of testosterone preceding standard gonadotrophin ovarian stimulation under pituitary suppression was used. In Group 2 (n = 31 patients), ovarian stimulation was carried out with high-dose gonadotrophin in association with a minidose GnRH agonist protocol. The primary end-point was the incidence of low-responder patients. The main secondary outcome was the incidence of patients reaching ovum retrieval. The percentage of cycles with low response was significantly lower in Group 1 than in Group 2 (32.2 versus 71% 95% confidence interval for the difference, 15.7-61.6; P < 0.05). The number of patients with ovum retrieval tended to be higher in Group 1 than in Group 2 (80.6 versus 58.1% P = 0.09), the difference reaching statistical significance (81.2 versus 41.1%; P < 0.05) when only patients having normal basal FSH levels (16 and 17 patients in Groups 1 and 2, respectively) were considered. Pretreatment with transdermal testosterone may improve the ovarian sensitivity to FSH and follicular response to gonadotrophin treatment in previous low-responder IVF patients. This approach leads to an increased follicular response compared with a high-dose gonadotrophin and minidose GnRH agonist protocol.


Identification of socio-demographic, occupational, and societal factors for guiding suicide prevention: A cohort study of Swiss male workers (2000-2014).
We modeled suicidal rate among Swiss working-age males, considering three groups of factors at socio-demographic, occupational, and societal levels jointly. Our goal was twofold: to verify the effect of occupation after adjustment for non-occupational factors and to identify protective and risk factors relevant for suicide prevention in working male adults. The study population included all men aged [18-65] years at the 2000 population census and followed up within the Swiss National Cohort (SNC). The risk of suicide was modeled using Poisson regression. The cohort comprised 1,534,564 men and 4371 deaths by suicide. Suicide rate varied significantly according to age, civil status, nationality, highest education achieved, and socio-professional category at socio-demographic level; occupation, occupational activity branch, weekly working hours, and home-to-work commute time at occupational level; calendar period of death, region, religious affiliation, and volunteering activity at societal level. After adjustment for non-occupational factors, agricultural and fishery laborers, military and civil security workers, and health and social workers were identified as high-risk groups with respect to suicide. This study evidenced a complex web of factors at socio-demographic, occupational, and societal levels behind the suicide in Swiss male workers and identified the most at-risk groups, deserving targeted prevention efforts.


Hydroxypropyl methylcellulose acetate succinate-based spray-dried dispersions: an overview.
Spray-dried dispersions (SDDs) of low-solubility drugs have been prepared using the polymer hydroxypropyl methylcellulose acetate succinate (HPMCAS). For a variety of drug structures, these SDDs provide supersaturation in in vitro dissolution determinations and large bioavailability increases in vivo. In bile-salt/lecithin in vitro solutions, these SDDs provide amorphous drug/polymer colloids and an increased concentration of free drug and drug in micelles relative to crystalline or amorphous drug. As dry powders, the SDDs are a single amorphous phase in which the drug remains amorphous and dispersed and does not crystallize over storage times relevant for practical drug products. A melting temperature (Tm)/glass-transition temperature (Tg) (K/K) versus log P map for 139 compounds formulated as SDDs provides a perspective on an appropriate formulation strategy for low-solubility drugs with various physical properties.


Identification of 18F-FDG PET/CT Parameters Associated with Weight Loss in Patients with Esophageal Cancer.
18F-FDG PET-CT is routinely performed as part of the initial staging of numerous cancers. Other than having descriptive, predictive and prognostic values for tumors, 18F-FDG PET-CT provides full-body data, which could inform on concurrent pathophysiological processes such as malnutrition. To test this hypothesis, we measured the 18F-FDG uptake in several organs and evaluated their association with weight loss in patients at diagnosis of esophageal cancer. Forty-eight patients were included in this retrospective monocentric study. 18F-FDG uptake quantification was performed in the brain, the liver, the spleen, bone marrow, muscle and the esophageal tumor itself and was compared between patients with different amounts of weight loss. We found that Total Lesion Glycolysis (TLG) and peak Standardized Uptake Values (SUVpeak) measured in the brain correlated with the amount of weight loss: TLG was, on average, higher in patients who had lost more than 5% of their usual weight, whereas brain SUVpeak were, on average, lower in patients who had lost more than 10% of their weight. Higher TLG and lower brain SUVpeak were associated with worse OS in the univariate analysis. This study reports a new and significant association between 18F-FDG uptake in the brain and initial weight loss in patients with esophageal cancer.


Acquaintance with the actuality: community diagnosis programme of Kathmandu Medical College at Gundu village, Bhaktapur, Nepal.
In Nepal, various field programs such as community diagnosis programmes (CDP) have been initiated to make the education of doctors, nurses and dentists more community oriented and relevant and suited to the health care scenario. Community diagnosis refers to the identification and quantification of the health problems in a community and identification of their correlates for the purpose of defining those individuals or groups at risk or those in need of health care. The article presents the main activities of community diagnosis as a core component of community-based education for the medical students at Kathmandu Medical College, Kathmandu, Nepal. A 4 weeks' Community Diagnosis Programme was conducted by MBBS II students (9th Batch) of the Kathmandu Medical College under the supervision of the Department of Community Medicine in November 2006 in the rural community of Gundu VDC (village development committee). The tools used included pre-tested questionnaires, weighing machines, measuring tapes, stethoscopes and sphygmomanometers. After the data collection and compilation, the students presented their findings in oral presentations, accompanied by a written report, including essential recommendations for improving the health status of these communities. The students benefited from the necessary process of integrating clinical skills and a public health approach, so as to enhance their epidemiological thinking and be of greater use to the communities where they will practice. The community also benefited by achievement of behavioral changes leading to healthier lifestyles and increased awareness of health-related matters and their role in quality of life. CDP is a way to practically demonstrate that the link between a medical college and society is possible. That is, a medical college can serve the community and thus society, with specific activities to improve health and the skills of students who will serve as future health professionals.


Differential activities of the ubiquitin-proteasome system in neurons versus glia may account for the preferential accumulation of misfolded proteins in neurons.
A variety of neurological disorders and polyglutamine (polyQ) diseases are caused by misfolded proteins. The common feature of these diseases is late-onset cellular degeneration that selectively affects neurons in distinct brain regions. polyQ diseases, including Huntington's disease (HD), present a clear case of selective neurodegeneration caused by polyQ expansion-induced protein misfolding, which also leads to predominant inclusions in neuronal nuclei. It remains unclear how these ubiquitously expressed disease proteins selectively kill neurons. In HD, mutant huntingtin accumulates in both neurons and glia, but more neuronal cells display huntingtin aggregates. These aggregates colocalize with components of the ubiquitin-proteasome system (UPS), which plays a critical role in clearing misfolded proteins. Using fluorescent reporters that reflect cellular UPS activity, we found that UPS activity in cultured neurons and glia decreases in a time-dependent manner. Importantly, UPS activity is lower in neurons than in glia and also lower in the nucleus than the cytoplasm. By expressing the UPS reporters in glia and neurons in the mouse brain, we also observed an age-dependent decrease in UPS activity, which is more pronounced in neurons than glial cells. Although brain UPS activities were similar between wild-type and HD 150Q knock-in mice, inhibiting the UPS markedly increases the accumulation of mutant htt in cultured glial cells. These findings suggest that the lower neuronal UPS activity may account for the preferential accumulation of misfolded proteins in neurons, as well as their selective vulnerability.


The Process and Impact of Stakeholder Engagement in Developing a Pediatric Intensive Care Unit Communication and Decision-Making Intervention.
Stakeholder-developed interventions are needed to support pediatric intensive care unit (PICU) communication and decision-making. Few publications delineate methods and outcomes of stakeholder engagement in research. We describe the process and impact of stakeholder engagement on developing a PICU communication and decision-making support intervention. We also describe the resultant intervention. Stakeholders included parents of PICU patients, healthcare team members (HTMs), and research experts. Through a year-long iterative process, we involved 96 stakeholders in 25 meetings and 26 focus groups or interviews. Stakeholders adapted an adult navigator model by identifying core intervention elements and then determining how to operationalize those core elements in pediatrics. The stakeholder input led to PICU-specific refinements, such as supporting transitions after PICU discharge and including ancillary tools. The resultant intervention includes navigator involvement with parents and HTMs and navigator-guided use of ancillary tools. Subsequent research will test the feasibility and efficacy of our intervention.


Light and temperature effects on miR156 transgenic switchgrass flowering: A simulated latitudinal study.
The control of flowering in perennial grasses is an important trait, especially among biofuel feedstocks. Lignocellulosic biomass may be increased commensurate with decreased or delayed flowering as the plant allocates energy for stems and leaves harvested for bioenergy at the end of the growing season. For transgenic feedstocks, such as switchgrass (Panicum virgatum L.) grown in its geographic center of distribution, it is foreseeable that regulators may require greatly decreased gene flow frequencies to enable commercialization. Transgenic switchgrass with various overexpression levels of a rice microRNA gene, miR156, when grown in field conditions, holds promise for decreased flowering, yielding high biomass, and altered cell wall traits, which renders it as a potential crossing partner for further breeding with switchgrass lines for decreased recalcitrance. In the current research, we simulated a latitudinal cline in controlled growth chamber experiments for various individual sites from the tropics to cool-temperate conditions which included weekly average high and low temperatures and day lengths over the switchgrass growing season for each simulated site: Guayaquil, Ecuador; Laredo, Texas, USA; and Brattleboro, Vermont, USA. Flowering and reproduction among transgenic lines with low (T-14 and T-35)-to-moderate (T-27 and T-37) overexpression of miR156 were assessed. Lower simulated latitudes (higher temperatures with low-variant day length) and long growing seasons promoted flowering of the miR156 transgenic switchgrass lines. Tropical conditions rescued the flowering phenotype in all transgenic lines except T-27. Higher numbers of plants in lines T-35 and T-37 and the controls produced panicles, which also occurred earlier in the study as temperatures increased and day length decreased. Line T-14 was the exception as more clonal replicates flowered in the cool-temperate (Vermont) conditions. Increased biomass was found in transgenic lines T-35 and T-37 in tropical conditions. No difference in biomass was found in subtropical (Texas) chambers, and two lines (T-14 and T-35) produced less biomass than the control in cool-temperate conditions. Our findings suggest that switchgrass plants engineered to overexpress miR156 for delayed flowering to promote bioconfinement and biomass production may be used for plant breeding at tropical sites.


Plant flavonoids--biosynthesis, transport and involvement in stress responses.
This paper aims at analysing the synthesis of flavonoids, their import and export in plant cell compartments, as well as their involvement in the response to stress, with particular reference to grapevine (Vitis vinifera L.). A multidrug and toxic compound extrusion (MATE) as well as ABC transporters have been demonstrated in the tonoplast of grape berry, where they perform a flavonoid transport. The involvement of a glutathione S-transferase (GST) gene has also been inferred. Recently, a putative flavonoid carrier, similar to mammalian bilitranslocase (BTL), has been identified in both grape berry skin and pulp. In skin the pattern of BTL expression increases from véraison to harvest, while in the pulp its expression reaches the maximum at the early ripening stage. Moreover, the presence of BTL in vascular bundles suggests its participation in long distance transport of flavonoids. In addition, the presence of a vesicular trafficking in plants responsible for flavonoid transport is discussed. Finally, the involvement of flavonoids in the response to stress is described.


New analysis technique for multistability detection.
Systems with counter-clockwise input-output (I-O) dynamics were recently introduced in order to study the convergence of positive feedback loops (possibly to many different equilibrium states). The author shows how this notion can be used to perform bifurcation analysis and globally predict multistability of a closed-loop feedback interconnection just by using the knowledge of steady-state I-O responses of the systems. To illustrate the theory, this method is then applied to a recently published model of mitogen activated protein kinase (MAPK) cascade. Furthermore, some examples (mainly motivated by molecular biology) of systems that enjoy the property are presented and discussed.


Utilization of swine wastewater as a feedstock for the production of polyhydroxyalkanoates by Azotobacter vinelandii UWD.
Azotobacter vinelandii UWD produced 0.69 g.l(-1) poly(hydroxybutyrate-co-hydroxyvalerate, PHBV) with 7.9 mol% hydroxyvalerate (HV) from twofold-diluted swine wastewater (SW). When supplemented with 20 g.l(-1) glucose, twofold-diluted SW increased copolymer production by 8.6 times. When three organic acids (acetate, propionate and butyrate) present in SW were supplemented with 20 g.l(-1) glucose, PHBV production was comparable (5.5 g.l(-1)) to that in the case of using twofold-diluted SW supplemented with 20 g.l(-1) glucose. However, the HV level (1.1-1.3 mol%) was very low. The component in SW contributing to copolymer production was found to be valerate. By 20 mM valerate 0.2 g.l(-1) PHBV with 44.6 mol% HV was produced. With 30 g.l(-1) glucose supplementation, 4.0 g.l(-1) PHBV with 22 mol% HV was produced. The optimal ratios of carbon to phosphorus (C : P) and to nitrogen (C : N) were 165 : 1 and 22 : 1, respectively.


Converging Medial Frontal Resting State and Diffusion-Based Abnormalities in Borderline Personality Disorder.
The psychological profile of patients with borderline personality disorder (BPD), with impulsivity and emotional dysregulation as core symptoms, has guided the search for abnormalities in specific brain areas such as the hippocampal-amygdala complex and the frontomedial cortex. However, whole-brain imaging studies so far have delivered highly heterogeneous results involving different brain locations. Functional resting-state and diffusion magnetic resonance imaging data were acquired in patients with BPD and in an equal number of matched control subjects (n = 60 for resting and n = 43 for diffusion). While mean diffusivity and fractional anisotropy brain images were generated from diffusion data, amplitude of low-frequency fluctuations and global brain connectivity images were used for the first time to evaluate BPD-related brain abnormalities from resting functional acquisitions. Whole-brain analyses using a p = .05 corrected threshold showed a convergence of alterations in BPD patients in genual and perigenual structures, with frontal white matter fractional anisotropy abnormalities partially encircling areas of increased mean diffusivity and global brain connectivity. Additionally, a cluster of enlarged amplitude of low-frequency fluctuations (high resting activity) was found involving part of the left hippocampus and amygdala. In turn, this cluster showed increased resting functional connectivity with the anterior cingulate. With a multimodal approach and without using a priori selected regions, we prove that structural and functional abnormality in BPD involves both temporolimbic and frontomedial structures as well as their connectivity. These structures have been previously related to behavioral and clinical symptoms in patients with BPD.


Expression and regulation of a Vibrio alginolyticus sucrose utilization system cloned in Escherichia coli.
A halotolerant collagenolytic Vibrio alginolyticus strain isolated from salted hides had intracellular sucrase activity and did not secret sucrase into the medium. The strain actively transported sucrose by a sucrose-inducible, Na+-independent process. A 10.4-kilobase DNA fragment of V. alginolyticus DNA was cloned into Escherichia coli. The recombinant E. coli(pVS100) could utilize sucrose as a sole carbon source. In contrast to V. alginolyticus, the recombinant E. coli produced both intra- and extracellular sucrase activities. Up to 20% of the total sucrase activity was in the supernatant. Sucrase synthesis in E. coli(pVS100) was inducible and was subject to glucose repression, which was relieved by cyclic AMP. Sucrose was actively transported by a sucrose-inducible, Na+-independent system in E. coli(pVS100). Sucrose uptake was inhibited by the addition of a proton conductor. The maximum velocity and apparent Km values of sucrose uptake for the V. alginolyticus strain and E. coli(pVS100) were 130 nmol/mg of protein per min and 50 microM and 6 nmol/mg of protein per min and 275 microM, respectively.


A confusing case report of pulmonary langerhans cell histiocytosis and literature review.
Pulmonary Langerhans Cell Histiocytosis (PLCH) is a rare disease. From the insidious onset and nonspecific manifestations, it is difficult to diagnose PLCH. To help improve the diagnosis and therapy options of adult PLCH, we present this case report and literature review about a confusing case of PLCH. In this report, we present a 37-year-old male PLCH case that was negative for CD1a and S100 expression. Smoking cessation and use of prescribed Spiriva appeared to improve the patient's symptoms. To the best of our knowledge, this is the first reported case of PLCH in which improved symptoms were seen with the use of Spiriva alone.The mechanism is not clear, but potentially has some relationship with dilating the airway, decreasing the mucous hypersecretion and promoting anti-inflammatory pathways. From this patient's case, we may be able to find more cases to then find other first line therapies for PLCH patients.


Palliative treatment of bone metastases.
Bone metastases are frequently one of the first signs of disseminated disease in cancer patients and are especially seen in patients with breast, prostate and lung cancer. The prognosis of these patients is generally poor and the treatment is primarily palliative: the intention is to relieve pain, prevent fractures, maintain activity and, if possible, to prolong survival. Besides analgesics the therapeutic options include local treatment with radiotherapy and/or surgery, and systemic treatment using chemotherapy, endocrine therapy, radioisotopes as well as bisphosphonates. Social and psychological supportive care is also very important. Radiotherapy plays an important role, but the other modalities such as bisphosphonates may also offer the same level of palliation, but their definite role has not been as clearly defined. There have been few randomized trials comparing the therapeutic options, and the criteria for assessing response to therapy have, in general, been poorly defined. There is a need for rigorous clinical investigations which assess the efficacy of the various therapeutic possibilities by using well-defined and validated response criteria such as pain and quality of life.


Membrane-encased polymer millirods for sustained release of 5-fluorouracil.
This article describes the design and development of a novel membrane-encased polymer millirod for the sustained release of an anticancer drug, 5-fluorouracil (5-FU). The millirod consists of two functional compartments: (1) an inner 5-FU-loaded monolithic millirod as the drug depot, and (2) an outer NaCl-impregnated polymer membrane to control the release rate of 5-FU. The inner millirod is fabricated by a compression-heat molding procedure to permit the entrapment of 5-FU particles in the poly(D,L-lactide-co-glycolide) (PLGA) matrix. The drug loading density is controlled at 30 w/w% to achieve a burst release of 5-FU (>90% of the drug are released within 48 h) from the monolithic millirod. The NaCl-impregnated PLGA membrane is generated by solvent casting and is then wrapped over the monolithic millirod to produce the membrane-encased millirod. Scanning electron microscopy shows that dissolution of NaCl particles produces a semipermeable polymer membrane to provide a sustained release of 5-FU. The membrane thickness and the density of NaCl particles inside the membrane are useful parameters to control the release kinetics of 5-FU. Under the experimental conditions in this study, sustained release of 5-FU [rates between 0.1 and 0.4 mg/(day. cm of millirod)] is achieved for 2 to 5 weeks in phosphate-buffered saline (pH 7.4) at 37 degrees C. Results from this study demonstrate that membrane-encased polymer millirods provide controllable sustained release kinetics for applications in intratumoral drug delivery.


The Preoccupation with Alcohol Scale: development and validation.
The purpose of the present study was to develop a psychometrically sound measure of preoccupation with alcohol in a group of young, heavy drinking men and to examine some correlates of this drinking style. A brief Preoccupation with Alcohol Scale (PAS) was derived that exhibited substantial internal consistency. Data from a sample of the 67 males indicated that higher PAS scores were significantly related to alcohol consumption and frequency of intoxication within many different contextual circumstances. The PAS was also related to alcohol problems after controlling for average daily alcohol consumption and frequency of intoxication, suggesting that scores on the PAS are related to, but not redundant with, level of alcohol consumption. Results from a cross-validation sample provided additional support for these findings. The authors suggest that a preoccupation with alcohol may be a cognitive-behavioral risk factor for the development of severe alcohol problems and alcoholism.


Bronchopulmonary dysplasia in very and extremely low birth weight infants - analysis of selected risk factors.
The aim of the study was to analyze the role of specific risk factors affecting the development and clinical course of BPD in infants born before 32 weeks of gestation with a birth weight ≤ 1500g. The study included 222 infants born and hospitalized at the Department of Neonatology, Polish Mother's Memorial Hospital-Research Institute. At their 28-th day of life, the patients were divided into two groups: with and without BPD. The grade of BPD severity was determined at 36 weeks of postmenstrual age. BPD was diagnosed in 117 (52.7%) of infants, 65 (55,6%) of them developed its mild, 29 (24,8%) moderate and 23 (19,7%) severe form. Infants with BPD had significantly lower gestational age than those without BPD: 27.0 weeks (IQR 26.0-28.3 weeks) vs. 30.0 weeks (IQR 29.3-31.0 weeks), and lower birth weight: 900g (IQR 740.0-1050.0g) vs. 1290g (IQR 1100.0-1370.0g). A significantly lower gestational age R=-0.70, p < 0.0001 and birth weight R=-0.66, p<0.0001 were observed in correspondence with the increase of BPD severity. In BPD group there were 72 (61.5%) male infants, whereas in that without BPD 54 (51.4%) of them, p=0.1290. In the group with mild form of BPD, there were 29 (44.6%) males, with moderate 23 (79.3%) and severe 20 (87.0%), p=0.0002. A statistically significant difference was found for: respiratory distress syndrome 116 (99.2%) vs. 83 (79.1%), p<0.0001, congenital infection 70 (59.8%) vs. 40 (38.1%), p=0.0012, patent ductus arteriosus 61 (52.1) vs. 28 (26.7), p=0.0001, complete prenatal steroid therapy 77 (65.8%) vs. 85 (81.0%), p=0.0112 and Apgar score of 1 min., p<0.0001 and 5 min., p<0.0001. In the group with BPD significantly more frequent were: intraventricular hemorrhage 87 (74.4%) vs. 37 (35.2%), p<0.0001, periventricular leukomalacia 11 (9.4%) vs. 0 (0.0%) p=0.0009 and retinopathy of prematurity 47 (40.2%) vs. 6 (5.7%), p<0.0001. No statistical significance was found for: premature rupture of membranes, the route of delivery, Ureaplasma spp. infection and necrotizing enterocolitis. Independent factors affecting the risk of BPD are: gestational age (OR 0.3213, p<0.0001), birth weight (OR 0.9968, p=0.0036), and respiratory distress syndrome (OR 3.9388; p=0.0142). Lower gestational age, low birth weight, respiratory distress syndrome, Apgar score, congenital infection, lack of prenatal steroid therapy, patent ductus arteriosus and male gender are the risk factors for the development of BPD.


Clinical characteristics of chemical sensitivity: an illustrative case history of asthma and MCS.
A case history of the induction of asthma and chemical sensitivity in a 42-year-old registered nurse illustrates several of the characteristic features of multiple chemical sensitivity (MCS). This patient's problems started shortly after moving into a new home under construction, with associated chemical exposures. Other MCS patients report the onset of the condition with other chemical exposures such as those encountered at their places of work or use of pesticides at their residences. Patients often describe a spreading phenomenon of increasing intolerance to commonly encountered chemicals at concentrations well tolerated by other people. Symptoms usually wax and wane with exposures, and are more likely to occur in patients or families with preexisting histories of migraine or with classical allergies. Idiosyncratic medication reactions (especially to preservative chemicals) are common in MCS patients, as are dysautonomia symptoms (such as vascular instability) and poor temperature regulation. Myalgia and joint pains and food intolerance are common features as well. Contamination with xenobiotic chemicals is frequently found in these patients when they are tested. Reactive airways dysfunction syndrome is a recently identified condition that exhibits features of both asthma and chemical sensitivity. MCS patients frequently have patterns of neurotoxic brain metabolism that can be confirmed on single photo emission computed tomography imaging.


Links of Adolescents Identity Development and Relationship with Peers: A Systematic Literature Review.
According to Erik Erikson, the main task of adolescents is to solve the crisis of identity versus role confusion. Research has shown that a stable and strong sense of identity is associated with better mental health of adolescents. Good relationships with peers are also linked with better emotional and psychological well-being of adolescents. However, there is a lack of reviews of studies in the scientific literature examining the relationship between the adolescents' identity development and relationships with peers. The aims of this article were to analyze links between adolescent identity development and relationships with peers identified from a literature review, summarize the results, and discuss the theoretical factors that may predict these relationships. A systematic literature review. Analysis of findings from the systematic literature review revealed that a good relationship with peers is positively related to adolescent identity development, but empirical research in this area is extremely limited. The links between adolescents' identity development and their relationship with peers are not completely clear. The possible intermediate factors that could determine the relationship between adolescent identity development and their relationships with peers are discussed. Further empirical researches is needed in this area.


Development of pigment-dispersing hormone-immunoreactive neurons in the American lobster: homology to the insect circadian pacemaker system?
We have examined the development of pigment-dispersing hormone (PDH)-immunoreactive neurons in embryos of the American lobster Homarus americanus Milne Edwards, 1837 (Decapoda, Reptantia, Homarida) by using an antiserum against beta-PDH. This peptide is detectable in the terminal medulla of the eyestalks and the protocerebrum where PDH immunoreactivity is present as early as 20% of embryonic development. During ontogenesis, an elaborate system of PDH-immunoreactive neurons and fibres develops in the eyestalks and the protocerebrum, whereas less labelling is present in the deuto- and tritocerebrum and the ventral nerve cord. The sinus gland is innervated by PDH neurites at hatching. This pattern of PDH immunoreactivity has been compared with that found in various insect species. Neurons immunoreactive to pigment-dispersing factor in the medulla have been shown to be a central component of the system that generates the circadian rhythm in insects. Our results indicate that, in view of the position of the neuronal somata and projection patterns of their neurites, the immunolabelled medulla neurons in insects have homologous counterparts in the crustacean eyestalk. Since locomotory and other activities in crustaceans follow distinct circadian rhythms comparable with those observed in insects, we suggest that PDH-immunoreactive medulla neurons in crustaceans are involved in the generation of these rhythms.


Increased circulating uric acid aggravates heart failure via impaired fatty acid metabolism.
Increased circulating uric acid (UA) concentration may disrupt cardiac function in heart failure patients, but the specific mechanism remains unclear. Here, we postulate that hyperuremia induces sterol regulatory element binding protein 1 (SREBP1), which in turn activate hepatic fatty acid biosynthesis response, leading to cardiac dysfunction. Increased circulating uric acid was observed in heart failure patients and inversely correlated to cardiac function. Besides, uric acid correlated to circulating lipids profile based on metabolomics in heart failure patients. Using cultured human hepatoellular carcinomas (HepG2) and Tg(myl7:egfp) zebrafish, we demonstrated that UA regulated fatty acid synthase (FASN) via SREBP1 signaling pathway, leading to FFA accumulation and impaired energy metabolism, which could be rescued via SREBP1 knockdown. In ISO treated zebrafish, UA aggravated heart failure via increased cardiovascular cavity size, decreased heart beats, pericardial edema and long-stretched heart deformation. Our findings suggest that UA-SREBP1-FASN signaling exacerbates cardiac dysfunction during FFA accumulation. Identification of this mechanism may help in treatment and prevention of heart failure.


[Analysis of amino acid composition of skim milk and buttermilk for the production of dairy drink when introducing whey protein hydrolysate].
The imbalance of macronutrient composition of people's diets determines the relevance of the functional foods development - sources of protein and essential amino acids. The aim of the work was to analyze the amino acid composition and determine the functional significance of the product based on skim milk and buttermilk byadding whey protein hydrolysate. Material and methods. The control options were samples of skimmed milk, buttermilk and their mixtures in a 1:1 ratio. From 1 to 3% of the whey protein hydrolysate with a degree of hydrolysis of about 60% of peptide bonds were added to the same milk base samplesin the experimental options. The amino acid composition was analyzed by high performance liquid chromatography using a cation exchange analyzer and subsequent post-column derivatization with ninhydrin. Results and discussion. The content of essential amino acids per 100 g of whey protein hydrolysate (WPH) is 50.6-168.0% from the adequate level of their daily intake, while there are only 3.0-22.3 and 2.6-19.9% in skimmed milk and buttermilk, respectively. Despite the practically equal protein content in skimmed milk and buttermilk 3.36±0.02 and 3.09±0.01%, respectively, the absolute content of all essential amino acids in buttermilk is lower than in skimmed milk. This can be explained by differences in the qualitative composition of proteins in these types of dairy raw materials. Conclusion. The amino acid composition of the milk base, consisting of buttermilk and skimmed milk mixture in a 1:1 ratio, can be presented as «functional» product in relation to Val, Ile, Leu, Lis, Trp and Tyr, due to the addition of 3% WPH, because the product portion of 200 g provides 15% of adequate daily intake of these essential amino acids. There is the reason to include additional information: low-fat, low-calorie, contains only natural sugars and a source of protein for people whose protein requirement does not exceed 99 grams per day in the labeling of the developed product, in addition to its nutritional and energy value.


Prevalence of Sleep Problems Among Chinese Medical Students: A Systematic Review and Meta-Analysis.
Sleep is a necessary physiological process, which is closely related to cognitive function, emotion, memory, endocrine balance, and immunity. The prevalence of sleep problems continues to rise in Chinese medical students, which has a potential influence on living and work. This study aimed to observe the prevalence of sleep problems among medical students in China. The included cross-sectional studies on the prevalence of sleep problems of medical students in China were retrieved from PubMed, Embase, the Cochrane Database of Systematic Reviews, CNKI, and Wanfang database. An 11-item checklist recommended by the Agency for Healthcare Research and Quality was adopted to evaluate the methodological quality of the included studies. Software Stata 12.0, SPSS 26.0, and R were used to analyze the data. Registration: PROSPERO, CRD 42021237303. The prevalence of sleep problems among Chinese medical students was 27.38%. The subgroup analysis showed significant differences in the prevalence of sleep problems among different regions, educational backgrounds, grades, and University types. The region, latitude, and gross domestic product (GDP) were significant heterogeneous sources of sleep problems. The prevalence is positively correlated with latitude and negatively correlated with GDP per capita. Regular screening and appropriate intervention are recommended for these mental health problems. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021237303, identifier: CRD42021237303.


Car accidents in cellular automata models for one-lane traffic flow.
Conditions for the occurrence of car accidents are introduced in the Nagel-Schreckenberg model. These conditions are based on the thought that a real accident depends on several parameters: an unexpected action of the car ahead (sudden stop or abrupt deceleration), the gap between the two cars, the velocity of the successor car and its delayed reaction time. We discuss then the effect of this delayed reaction time on the probability of traffic accidents. We find that these conditions for the occurrence of car accidents are necessary for modeling realistic accidents.