[The human Y chromosome].
Recent findings concerning the human Y chromosome are reviewed. Normally the presence of the Y chromosome is related to male differentiation; however until recently nothing was known about chromosome Y and the development of the testis at the molecular level. Initially the most plausible assumption in this field was the "H-Y hypothesis" which suggested that the presence of a male specific antigen called H-Y, controlled by a gene(s) on the Y chromosome, was responsible for the differentiation of the primitive gonad into a testis. An alternative was a series of DNA sequences termed Bkm which were thought to play an important role in sex determination. These two hypothesis were refuted. More recently, molecular studies in XX males have shown the presence of Y-DNA in their genome suggesting that a small fragment of the Y (probably a single gene) is responsible for testis development in the majority of these patients. This gene has been termed TDF or ZFY and encodes a protein that could act as a regulating factor of the male pathway. Also reviewed are the actions of various genes recently assigned to the Y chromosome.


Effects of home visits by paraprofessionals and by nurses: age 4 follow-up results of a randomized trial.
To examine the effects of prenatal and infancy home visiting by paraprofessionals and by nurses from child age 2 through age 4 years. We conducted, in public and private care settings in Denver, Colorado, a randomized, controlled trial with 3 arms, ie, control, paraprofessional visits, and nurse visits. Home visits were provided from pregnancy through child age 2 years. We invited 1178 consecutive, low-income, pregnant women with no previous live births to participate, and we randomized 735; 85% were unmarried, 47% Mexican American, 35% white non-Mexican American, 15% black, and 3% American Indian/Asian. Outcomes consisted of maternal reports of subsequent pregnancies, participation in education and work, use of welfare, marriage, cohabitation, experience of domestic violence, mental health, substance use, and sense of mastery; observations of mother-child interaction and the home environment; tests of children's language and executive functioning; and mothers' reports of children's externalizing behavior problems. Two years after the program ended, women who were visited by paraprofessionals, compared with control subjects, were less likely to be married (32.2% vs 44.0%) and to live with the biological father of the child (32.7% vs 43.1%) but worked more (15.13 months vs 13.38 months) and reported a greater sense of mastery and better mental health (standardized scores [mean = 100, SD = 10] of 101.25 vs 99.31 and 101.21 vs 99.16, respectively). Paraprofessional-visited women had fewer subsequent miscarriages (6.6% vs 12.3%) and low birth weight newborns (2.8% vs 7.7%). Mothers and children who were visited by paraprofessionals, compared with control subjects, displayed greater sensitivity and responsiveness toward one another (standardized score [mean = 100, SD = 10] of 100.92 vs 98.66) and, in cases in which the mothers had low levels of psychologic resources at registration, had home environments that were more supportive of children's early learning (score of 24.63 vs 23.35). Nurse-visited women reported greater intervals between the births of their first and second children (24.51 months vs 20.39 months) and less domestic violence (6.9% vs 13.6%) and enrolled their children less frequently in preschool, Head Start, or licensed day care than did control subjects. Nurse-visited children whose mothers had low levels of psychologic resources at registration, compared with control group counterparts, demonstrated home environments that were more supportive of children's early learning (score of 24.61 vs 23.35), more advanced language (score of 91.39 vs 86.73), superior executive functioning (score of 100.16 vs 95.48), and better behavioral adaptation during testing (score of 100.41 vs 96.66). There were no statistically significant effects of either nurse or paraprofessional visits on the number of subsequent pregnancies, women's educational achievement, use of substances, use of welfare, or children's externalizing behavior problems. Paraprofessional-visited mothers began to experience benefits from the program 2 years after the program ended at child age 2 years, but their first-born children were not statistically distinguishable from their control group counterparts. Nurse-visited mothers and children continued to benefit from the program 2 years after it ended. The impact of the nurse-delivered program on children was concentrated on children born to mothers with low levels of psychologic resources.


An amplifiable and deletable locus of Streptomyces ambofaciens RP181110 contains a very large gene homologous to polyketide synthase genes.
Streptomyces ambofaciens RP181110 produces the macrolide polyketide spiramycin. Like many other Streptomyces species, the RP181110 strain is prone to genetic instability involving genomic rearrangements (deletions and/or amplifications) in the large unstable region of the genome. It has previously been demonstrated that the amplification of a particular locus (AUD205) affects spiramycin biosynthesis and, conversely, the loss of this amplification is correlated with the restoration of antibiotic production. This report focuses on a 0.93 kb reiterated fragment specific for the AUD205 locus. Sequencing of 3596 bp including this reiteration revealed the presence of an ORF (orfPS) whose potential product was highly homologous to the EryA and Raps proteins, responsible for the biosynthesis of erythromycin in Saccharopolyspora erythraea and rapamycin in Streptomyces hygroscopicus, respectively. orfPS encodes a protein with at least four successive domains: ketoacyl synthase, acyltransferase, ketoreductase and acyl carrier protein. This organization is very similar to most eryA and rap modules. The reiterated sequence corresponds to the acyltransferase domain. orfPS was transcribed during rapid growth and stationary phase in RP181110 and overtranscribed in the amplified mutant. Both these results suggest that the gene encodes a type I polyketide synthase and its reorganization is responsible for the loss of spiramycin production in the amplified strains.


Structural and functional analysis of a glutathione S-transferase from Ascaris suum.
A recombinant glutathione S-transferase (GST) (EC 22.214.171.124) from the parasitic nematode Ascaris suum (AsGST1) displays specific activity with a variety of model substrates and secondary products of lipid peroxidation. The AsGST1 interacts with a range of model inhibitors, haematin-related compounds, bile acids and anthelminthics. The reported variations in biochemical activity correlate with structural differences observed by homology modelling. Here, differences in the topography of the proposed substrate binding site between the AsGST1 and the host GSTs were identified. A rabbit polyclonal antiserum was raised against the glutathione-binding proteins of A. suum and specific antibodies against AsGST1 were affinity-purified using the recombinant protein. These antibodies were used to localize the AsGST1 in adult worms by immunohistochemical staining. The strongest immunostaining for AsGST1 was localized in the intestine in all worms examined. This suggests that the enzyme may be responsible for the metabolism of materials that are incorporated from the environment, as well as for molecules that are excreted or secreted from the parasite to the environment. It also demonstrates the accessibility of the enzyme to an inhibitor or blocking antibody. In addition, the structure and sequence of the gene encoding AsGST1 have been determined. Southern-blot analyses of the AsGST1 gene suggests that it is a single-copy gene. The nucleotide sequence analysis revealed that the gene is composed of four exons and three introns, and potential regulatory elements were identified in the 5' flanking sequence.


Testosterone response of cryptorchid and hypophysectomized rats to human chorionic gonadotrophin (hCG) stimulation.
The testosterone responses to a single injection of hCG (100 i.u.) in hypophysectomized (hypox.), cryptorchid or sham-operated rats were followed over a 5-day period. In sham-operated rats, hCG induced a biphasic rise in serum testosterone, peaks being observed at 2 and 72 h. Reduced testis weights, elevated FSH and LH levels and reduced serum testosterone levels were found after 4 weeks of cryptorchidism, but hCG stimulation resulted in a normal 2 h peak in serum testosterone. However, the secondary rise at 72 h in cryptorchid rats was significantly lower than sham-operated rats. Reduced testis weight and undetectable serum FSH and LH levels together with decreased testosterone levels were found 4 weeks after hypophysectomy. Serum testosterone levels rose 2 h after hCG in comparison to hypox. controls but this peak was significantly reduced compared with sham-operated rats. The second rise in serum testosterone began on day 2, peaking on day 4 at levels comparable to that seen in sham-operated rats after hCG. The in vitro basal and hCG stimulated secretion of testosterone by cryptorchid testes was greater than that secreted by normal rat testes (518.0 +/- 45.9 and 3337.6 +/- 304.1 pmol per testis per 4 h compared with 223.6 +/- 24.9 and 1312.9 +/- 141.4 pmol per testis per 4 h for normal rat testes). In cryptorchid animals a single injection of 100 i.u. hCG resulted in a pattern of in vitro refractoriness similar to normal rats, lasting from 12 h to 2 days, during which testosterone secretion was reduced to near basal levels. The in vitro basal and hCG-stimulated secretion of testosterone by hypox. rat testes was severely diminished compared with normal rat testes. The temporal pattern of in vitro secretion of testosterone from hypox. rat testes mimicked the in vivo serum testosterone pattern seen in these animals. This study demonstrates important differences in the in vivo and in vitro testosterone response to hCG after testicular damage.


Development of thermally stable red-emitting lead-free double-perovskite phosphors with an internal PLQY approaching 100.
White light-emitting diode (WLEDs), acting as a new generation of solid-state lighting, play a critical role in energy conservation. Red-emitting phosphors with high efficiency could effectively improve the quality of WLED devices. In this report, Eu3+-doped Ca2ScTaO6 luminescent materials have been successfully synthesized by a high-temperature solid-state method. Its crystal structure was confirmed to be a monoclinic lead-free double-perovskite material system with the space group P21/n by the X-ray diffraction patterns. The strongest emission peak was about 614 nm distributed to the 5D0 → 7F2 electric-dipole transition. Additionally, the optimal doping concentration was found to be 40 mol%, and the concentration quenching mechanism is assigned to d-d interactions. The Ca2ScTaO6:Eu3+ phosphors exhibited an ultrahigh internal quantum yield (about 100%) with good thermal stability (81.5% at 423 K compared with the emission intensity at 303 K). Furthermore, a WLED with a suitable correlated color temperature (4201 K) and a color rendering index (87.62) was fabricated. The phosphor-based polydimethylsiloxane light-emitting flexible film exhibited good luminescence, which is suitable to be utilized in flexible displays. The obtained results suggest that the high-efficiency red-emitting Ca2ScTaO6:Eu3+ phosphors are promising commercial candidates for use in near-ultraviolet-excited WLEDs.


[Partial jejunal volvulus due to a mesenteric cystic lymphangioma].
Mesenteric cysts are unusual benign tumours that include lymphangioma. Their clinical presentation is variable and acute symptoms can be produced due to complications. This tumour appears especially in childhood, and its prognosis after surgical removal is excellent. We present the case of a 15 year old female patient with symptoms of postprandial abdominal pain and palpation of smooth mass in hypogastrium. Radiological studies showed a big polilobular mass of cystic substance that included a portion of jejune with incomplete volvulus. The treatment was the removal of the cyst and a jejunal portion and the pathological diagnosis was mesenteric cyst lymphangioma. The patient is asymptomatic more than three years after the intervention.


Efficacy of Dietary Lipid Control in Healing High-Fat and High-Cholesterol Diet-Induced Fibrotic Steatohepatitis in Rats.
Nonalcoholic steatohepatitis is related to lifestyle, particularly to dietary habits. We developed diet-induced fibrotic steatohepatitis model stroke-prone spontaneously hypertensive 5/Dmcr (SHRSP5/Dmcr) rats showing steatosis, hepatic inflammation, and severe fibrosis induced by high-fat and -cholesterol (HFC) diet feeding. We aimed to clarify the efficacy of dietary intervention on the disease before and after the appearance of fibrosis. Male SHRSP5/Dmcr rats were divided into 9 groups; of these, 6 groups were fed control or HFC diet for several weeks and the remaining 3 groups represented the dietary intervention groups, which were fed the control diet after HFC diet feeding for 2 (before the appearance of fibrosis) or 8 (after the appearance of fibrosis) weeks. Dietary intervention before the appearance of fibrosis significantly improved the steatosis and reset the increased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and serum total cholesterol (TC) levels. However, dietary intervention after the appearance of fibrosis was unable to reset the levels of hepatic TC, serum ALT, and fibrogenesis-related markers and had only a minor influence on hepatic fibrosis, although it reset the increased expression of transforming growth factor (TGF)-β1 and α-smooth muscle actin (SMA). It was noted that dietary intervention improved the increased AST levels; however, aggregated CD68-positive cells were still observed around the fibrosis area, which may be related to the findings of inflammatory cytokine mRNAs. Taken together, dietary intervention for fibrotic steatohepatitis improved steatosis, although it could not completely improve fibrosis.


Adaptive plasticity during the development of colour vision.
Colour vision greatly enhances the discriminatory and cognitive capabilities of visual systems and is found in a great majority of vertebrates and many invertebrates. However, colour coding visual systems are confronted with the fact that the external stimuli are ambiguous because they are subject to constant variations of luminance and spectral composition. Furthermore, the transmittance of the ocular media, the spectral sensitivity of visual pigments and the ratio of spectral cone types are also variable. This results in a situation where there is no fixed relationship between a stimulus and a colour percept. Colour constancy has been identified as a powerful mechanism to deal with this set of problems; however, it is active only in a short-term time range. Changes covering longer periods of time require additional tuning mechanisms at the photoreceptor level or at postreceptoral stages of chromatic processing. We have used the trichromatic blue acara (Aequidens pulcher, Cichlidae) as a model system and studied retinal morphology and physiology, and visually evoked behaviour after rearing fish for 1-2 years under various conditions including near monochromatic lights (spectral deprivation) and two intensities of white light (controls). In general, long-term exposure to long wavelengths light had lesser effects than light of middle and short wavelengths. Within the cone photoreceptors, spectral deprivation did not change the absorption characteristics of the visual pigments. By contrast, the outer segment length of middle and long-wave-sensitive cones was markedly increased in the blue rearing group. Furthermore, in the same group, we observed a loss of 65% short-wave-sensitive cones after 2 years. These changes may be interpreted as manifestations of compensatory mechanisms aimed at restoring the balance between the chromatic channels. At the horizontal cell level, the connectivity between short-wave-sensitive cones and the H2 cone horizontal cells, and the spinule dynamics were both affected in the blue light group. This observation rules out the role of spinules as sites of chromatic feedback synapses. The light-evoked responses of H2 horizontal cells were also sensitive to spectral deprivation showing a shift of the neutral point towards short wavelengths in the blue rearing group. Interestingly, we also found an intensity effect because in the group reared in bright white light the neutral point was more towards longer wavelength than in the dim light group. Like the changes in the cones, the reactions of horizontal cells to spectral deprivation in the long wave domain can be characterised as compensatory. We also tested the spectral sensitivity of the various experimental groups of blue acara in visually evoked behaviour using the optomotor response paradigm. In this case, the changes in the relative spectral sensitivity were more complex and could not be explained by a simple extrapolation of the adaptive and compensatory processes in the outer retina. We conclude that the inner retina, and/or the optic tectum are also involved and react to the changes of the spectral environment. In summary, we have shown a considerable developmental plasticity in the colour vision system of the blue acara, where epigenetic adaptive processes at various levels of the visual system respond to the specific spectral composition of the surroundings and provide a powerful mechanism to ensure functional colour vision in different visual environments. We suggest that processes involving an active fine-tuning of the photoreceptors and the postreceptoral processing of chromatic information during ontogenetic development are a general feature of all colour vision systems. Such mechanisms would establish a functional balance between the various chromatic channels. This appears to be an essential condition for the cognitive systems to extract the relevant and stable information from the unstable and changing stimulus situation.


Extensive Homoplasy but No Evidence of Convergent Evolution of Repeat Numbers at MIRU Loci in Modern Mycobacterium tuberculosis Lineages.
More human deaths have been attributable to Mycobacterium tuberculosis than any other pathogen, and the epidemic is sustained by ongoing transmission. Various typing schemes have been developed to identify strain-specific differences and track transmission dynamics in affected communities, with recent introduction of whole genome sequencing providing the most accurate assessment. Mycobacterial interspersed repetitive unit (MIRU) typing is a family of variable number tandem repeat schemes that have been widely used to study the molecular epidemiology of M. tuberculosis. MIRU typing was used in most well-resourced settings to perform routine molecular epidemiology. Instances of MIRU homoplasy have been observed in comparison with sequence-based phylogenies, limiting its discriminatory value. A fundamental question is whether the observed homoplasy arises purely through stochastic processes, or whether there is evidence of natural selection. We compared repeat numbers at 24 MIRU loci with a whole genome sequence-based phylogeny of 245 isolates representing three modern M. tuberculosis lineages. This analysis demonstrated extensive homoplasy of repeat numbers, but did not detect any evidence of natural selection of repeat numbers, at least since the ancestral branching of the three modern lineages of M. tuberculosis. In addition, we observed good sensitivity but poor specificity and positive predictive values of MIRU-24 to detect clusters of recent transmission, as defined by whole-genome single nucleotide polymorphism analysis. These findings provide mechanistic insight, and support a transition away from VNTR-based typing toward sequence-based typing schemes for both research and public health purposes.


Vitality of the dentin-pulp complex in health and disease: growth factors as key mediators.
The vitality of the dentin-pulp complex, both during tissue homeostasis and after injury, is dependent on pulp cell activity and the signalling processes, which regulate the behavior of these cells. Research, particularly over the last ten to fifteen years, has led to a better understanding of the molecular control of cellular behavior. Growth factors play a pivotal role in signalling the events of tissue formation and repair in the dentin-pulp complex. Sequestration of growth factors in the dentin matrix during tissue formation provides a pool of these molecules, which may be released during injury and contribute to signalling of reparative events. Therapeutic intervention with recombinant growth factors also provides possibilities for control of cell activity during repair. Harnessing both endogenous and exogenous sources of growth factors can provide exciting opportunities for novel biological approaches to dental tissue repair and the blueprint for tissue engineering of the tooth. These approaches offer significant potential for improved clinical management of dental disease and maintenance of tooth vitality.


DMCA-GAN: Dual Multilevel Constrained Attention GAN for MRI-Based Hippocampus Segmentation.
Precise segmentation of the hippocampus is essential for various human brain activity and neurological disorder studies. To overcome the small size of the hippocampus and the low contrast of MR images, a dual multilevel constrained attention GAN for MRI-based hippocampus segmentation is proposed in this paper, which is used to provide a relatively effective balance between suppressing noise interference and enhancing feature learning. First, we design the dual-GAN backbone to effectively compensate for the spatial information damage caused by multiple pooling operations in the feature generation stage. Specifically, dual-GAN performs joint adversarial learning on the multiscale feature maps at the end of the generator, which yields an average Dice coefficient (DSC) gain of 5.95% over the baseline. Next, to suppress MRI high-frequency noise interference, a multilayer information constraint unit is introduced before feature decoding, which improves the sensitivity of the decoder to forecast features by 5.39% and effectively alleviates the network overfitting problem. Then, to refine the boundary segmentation effects, we construct a multiscale feature attention restraint mechanism, which forces the network to concentrate more on effective multiscale details, thus improving the robustness. Furthermore, the dual discriminators D1 and D2 also effectively prevent the negative migration phenomenon. The proposed DMCA-GAN obtained a DSC of 90.53% on the Medical Segmentation Decathlon (MSD) dataset with tenfold cross-validation, which is superior to the backbone by 3.78%.


Preliminary clinical experience with the 4 K3-dimensional microvideoscope (VITOM 3D) system for free flap head and neck reconstruction.
To demonstrate the use of a 4 K 3-dimensional microvideoscope (VITOM 3D) system for free flap head and neck reconstruction. Clinical human study of free flap harvesting and microvascular anastomosis in patients undergoing reconstruction after ablative surgery for head and neck carcinoma. The video shows the harvesting of a chimeric myofascial/fascio-cutaneous anterolateral thigh free flap and microvascular anastomosis using different techniques. The VITOM 3D exoscope system provided sufficient access, reach, and visualization to perform successfully free flap harvesting and microvascular anastomosis. Using the 3D glasses, both surgeons and nurses can have the same visualization throughout the entire procedure. We performed 10 arterial and venous anastomosis without significant complications. This study demonstrates the technical feasibility of free flap harvesting and microvascular anastomosis using the 4 K3-Dimensional Microvideoscope (VITOM 3D) System.


The interaction between Toxoplasma gondii and mammalian cells. I. Mechanism of entry and intracellular fate of the parasite.
Macrophage, fibroblast, and HeLa cell cultures have been infected with Toxoplasma gondii, and observations have been made on parasite entry and fate. A special procedure was devised for studying the entry of toxoplasmas by electron microscopy. Toxoplasmas were centrifuged onto the cells in the cold; fixation 1-3 min after warming yielded specimens showing numerous examples of parasites in the process of entering cells. The mechanism of entry into macrophages, fibroblasts, and HeLa cells was in all cases by phagocytosis. Micropseudopods were extended by the cells to envelop the attached parasites in a typical phagocytic vacuole. Apparently the toxoplasmas stimulated this response of HeLa cells and fibroblasts, cell types not usually phagocytic. No instance was seen of penetration of toxoplasmas through the cell membrane, or of parasites located free in the cytoplasm. Essentially all of the toxoplasmas that entered HeLa cells divided with a generation time of 9 hr; the parasites formed large rosettes situated in vacuoles, eventually leading to host cell rupture. Macrophages took in larger numbers of toxoplasmas than did HeLa cells, but approximately half of the parasites inside of macrophages degenerated within a few hours. The surviving toxoplasmas in macrophages divided every 8 hr, forming rosettes and eventually rupturing the cells.


Understanding Parenting Intentions Among Childfree Gay Men: A Comparison With Lesbian Women and Heterosexual Men and Women.
There is a growing interest in the parenting intentions of gay men. Prior research has found that gay men are less likely to become parents compared to their heterosexual and lesbian peers, but we know very little about why this discrepancy exists. Our first aim was to investigate whether the strength of parenting intentions is similar or different among childfree gay men compared to lesbian women, and heterosexual men and women. Our second aim was to explore the extent to which the theory of planned behavior (TPB) model (attitude, subjective norms, and self-efficacy) is universal in predicting the strength of parenting intentions across gender and/or sexual orientation. The study was based on a United States cross-sectional, internet-based survey of childfree people who want to become parents in the future. The sample consisted of 58 gay men, 66 lesbian women, 164 heterosexual people (128 women and 36 men). A Bayesian ANCOVA showed no support for a gender difference in the strength of parenting intentions. Moderate evidence was provided for gay men and lesbian women reporting a similar strength of parenting intentions compared to their heterosexual peers. Bayesian linear regression analyses showed that perceived positive and negative life changes were stronger predictors of the strength of parenting intentions for men than for women. Perceived positive life changes predicted the strength of parenting intentions similarily across sexual orientations. For gay men and lesbian women, perceived parental acceptance of future parenthood was a weaker predictor of the strength of parenting intentions compared to heterosexual people. Those who perceived parenthood as bringing positive life changes, especially for men, expressed stronger parenting intentions.


[Active computer systems for medical education: approach and implementation].
The methodological bases and ways of building and using the new type of the educational computer-aided systems for physicians, the Diagnostic trainer, are discussed in the paper. The user's work on the Diagnostic Trainer proceeds in the form of a game during which the system stimulates clinical cases while the user analyzes them. The Diagnostic Trainer uses its knowledge base for simulations and requires no clinical cases to be prepared beforehand. The Diagnostic Trainer never forces the user to do, but always fixes his/her attention on the available essential points and possible contradictions between the specific clinical case and the user's strategy to make a decision.


First branchial arch cyst in an elderly patient: diagnostic dilemma and subsequent management.
The branchial system plays a significant role in the embryological development of the many internal and external human body structures. Failure of normal development of these systems may result in branchial system anomalies. Anomalies of the first branchial cleft are rare and account for 1-8% of all branchial anomalies. They have an incidence of 1 per 1 million births, most of which are diagnosed in early childhood. We present an unusual case of a first branchial arch cyst in an elderly gentleman: a 65-year-old man who presented with a persistent swelling in the left pre-auricular region with no associated sinus, fistulae or lymphadenopathy and with an intact facial nerve. Investigations including fine needle aspiration, ultrasound and magnetic resonance imaging led to the diagnosis of a lesion of salivary origin and an extracapsular dissection was undertaken. The histological appearance on excision was, however, in keeping with a first arch branchial cyst. In conclusion, the nonspecific clinical and radiological presentation of first branchial arch anomalies may lead to difficulty and often delay in the diagnosis of these lesions, particularly in elderly patients as it is more often associated with childhood and adolescence. A high level of suspicion is mandatory to prevent inappropriate management in the form of incision and drainage, which further increases the risk of recurrence and facial nerve injury at the time of formal excision due to scarring.


The role of hepatic progenitor cells in predicting response to therapy in Egyptian patients with chronic hepatitis C, genotype 4.
Interferon therapy is used as a line of treatment of chronic hepatitis C virus (HCV) in several areas of the world including Egypt. Our aim was to investigate the value of hepatic progenitor cells (HPCs) in predicting response of patients with chronic HCV, genotype 4 to pegylated interferon (PEGIFN) plus ribavirin (RBV) therapy. Pre-treatment liver biopsies obtained from 110 patients with chronic HCV, genotype 4 were examined immunohistochemically for HPCs using cytokeratin19. The mean number of HPCs as ductular reaction (DR) and as isolated progenitor cells (IPCs) was counted in each case. The patients were classified into: those with sustained virological response (SVR) and those who did not achieve SVR. The results were compared between the two groups. Also, the relationships between HPCs and other clinico-pathologic variables were estimated using multivariate analysis. The mean number of HPCs was the only independent predictor of therapeutic response, being significantly higher in non-responders (P = 0 for DR and P = 0.03 for IPCs). On the other hand, fibrosis stage and steatosis were the only independent factors which showed a significant direct association with the mean number of HPCs in the form of DR and IPCs (P = 0 for each). The number of HPCs provides prognostic information in chronic HCV since it is significantly associated with stage of fibrosis. More importantly, it can be used as a marker to predict response of patients with chronic HCV to PEGIFN plus RBV therapy.


Methicillin-resistant Staphylococcus aureus as a community organism.
An increase in methicillin-resistant Staphylococcus aureus (MRSA) infections prompted a study of MRSA during a 21-month period in a 600-bed university hospital in southern Texas. MRSA cases were classified as community, nosocomial, or transfer cases. A case-control study of risk factors for community MRSA compared with community methicillin-susceptible S. aureus (MSSA) was performed. Pulsed field gel electrophoresis (PFGE) of whole cell DNA typing was used as a marker of strain identity for 31 consecutive isolates collected during the last 8 months of the study. During the 21 months there were 170 patients with MRSA infection or colonization, an incidence of 0.2 per 1,000 patient-days. Ninety-nine (58%) of 170 isolates were from community cases; the community to nosocomial case ratio was 2:1. No significant risk factors differentiated patients with community MRSA compared with community MSSA. Most community MRSA isolates studied (15 [68%] of 22) had distinct PFGE patterns, as did many nosocomial MRSA isolates (4 [44%] of 9). MRSA isolates were commonly present on admission to the hospital, and multiple MRSA strains were demonstrated among both community and hospital isolates.


Angiogenic nature of the "intravascular bronchioloalveolar tumor" of the lung: an electron microscopic study.
An intravascular bronchioloalveolar tumor of lung (IVBAT) was studied with electron microscopy. Based on ultrastructural evidence and information obtained from the literature, we propose the following: (1) IVBAT is a true pulmonary neoplasm with distinctive morphologic features; (2) it consists of cells with endothelial characteristics and is probably derived from multipotential mesenchymal reserve cells; (3) it is not related to the typical bronchioloalveolar tumor of lung; (4) a more appropriate designation for this unusual pulmonary neoplasm is "sclerosing angiogenic tumor."


Caspofungin-induced severe toxic epidermal necrolysis.
To report a case of suspected caspofungin-induced toxic epidermal necrolysis (TEN). An 86-year-old man had a right femur intertrochanteric fracture and right proximal humerus fracture due to an accidental fall. Disseminated Candida krusei infection complicated the postoperative course. Candidemia persisted despite 25 days of treatment with parenteral fluconazole. The antifungal agent was changed to intravenous caspofungin. Immediately after administration of a caspofungin 70-mg loading dose, a transient skin rash developed, which resolved after discontinuation of the drug and immediate treatment with intravenous diphenhydramine 30 mg and methylprednisolone 40 mg. Six days later, a caspofungin 70-mg loading dose was given again due to increasing sepsis. Erythematous and purpuric macules and plaques developed the next day and rapidly progressed to extensive erythema, exfoliation, blisters, and skin erosions. A dermatologist was consulted and TEN was diagnosed. The patient was treated with intravenous hydrocortisone 100 mg every 8 hours and diphenhydramine 30 mg every 8 hours. The skin lesions progressed unrelentingly and the patient died of refractory shock 6 days later. TEN is a rare but life-threatening systemic and cutaneous disease that is most often the result of an adverse drug reaction. It usually manifests as fever and influenza-like symptoms 1-3 days before the development of mucocutaneous lesions, namely erythema and erosions of the buccal, ocular, and genital mucosa and characteristic epidermal detachment. The precise pathogenesis is not fully understood. Several models have been described, including immunopathology, genetic susceptibility, Fas-Fas ligand, perforin/granzyme, and cytokine dysregulation. Use of the Naranjo probability scale indicated a probable relationship between caspofungin and the development of TEN in this patient. This is the first report of caspofungin-induced TEN. Health-care professionals are advised to be aware of the early presentations of TEN in patients receiving caspofungin.


Mortality and Macrovascular Risk in Elderly With Hypertension and Diabetes: Effect of Intensive Drug Therapy.
This study identifies the effect of intensive drug therapy (IDT) in individuals age 65+ with diabetes (type 2 diabetes mellitus (T2D)) and hypertension on all-cause death, congestive heart failure (CHF), hospitalization for myocardial infarction (MI), and stroke or transient ischemic attack (TIA). Individuals from the Medicare 5% dataset with hypertension and T2D undergoing IDT for these conditions were propensity score matched to a nonintensive drug-therapy group. Hazard ratios (HRs) were obtained using the Cox proportional hazard model. IDT was associated with increased risk of CHF (HR 2.32; 95% confidence interval (CI) 2.32-2.38), MI (HR 4.27; 95% CI 4.05-4.52), and stroke or TIA (HR 1.80; 95% CI 1.70-1.89) but decreased risk of death (HR 0.95; 95% CI 0.93-0.97). Risk for CHF (HR 0.73; 95% CI 0.71-0.73), MI (HR 0.64; 95% CI 0.62-0.67), stroke or TIA (HR 0.82; 95% CI 0.78-0.86), and death (HR 0.29; 95% CI 0.28-0.29) was decreased by adherence to diabetes management guidelines. Use of IDT in a high-risk population delays death but not severe macrovascular outcomes. Protective effects of IDT in high-risk patients likely outweigh polypharmacy-related health concerns.


Diminution of oxalate induced renal tubular epithelial cell injury and inhibition of calcium oxalate crystallization in vitro by aqueous extract of Tribulus terrestris.
Recurrence and persistent side effects of present day treatment for urolithiasis restrict their use, so an alternate solution, using phytotherapy is being sought. The present study attempted to evaluate the antilithiatic properties of Tribulus terrestris commonly called as "gokhru" which is often used in ayurveda to treat various urinary diseases including urolithiasis. The activity of Tribulus terrestris was investigated on nucleation and the growth of the calcium oxalate (CaOx) crystals as well as on oxalate induced cell injury of NRK 52E renal epithelial cells. Tribulus terrestris extract exhibited a concentration dependent inhibition of nucleation and the growth of CaOx crystals. When NRK-52E cells were injured by exposure to oxalate for 72 h, Tribulus terrestris extract prevented the injury in a dose-dependent manner. On treatment with the different concentrations of the plant, the cell viability increased and lactate dehydrogenase release decreased in a concentration dependent manner. The current data suggests that Tribulus terrestris extract not only has a potential to inhibit nucleation and the growth of the CaOx crystals but also has a cytoprotective role. Our results indicate that it could be a potential candidate for phytotherapy against urolithiasis.


(CA/GT)(n) microsatellites affect homologous recombination during yeast meiosis.
One of the most common microsatellites in eukaryotes consists of tandem arrays of the dinucleotide GT. Although the study of the instability of such repetitive DNA has been extremely fruitful over the last decade, no biological function has been demonstrated for these sequences. We investigated the genetic behavior of a region of the yeast Saccharomyces cerevisiae genome containing a 39-CA/GT dinucleotide repeat sequence. When the microsatellite sequence was present at the ARG4 locus on homologous chromosomes, diploid cells undergoing meiosis generated an excess of tetrads containing a conversion of the region restricted to the region of the microsatellite close to the recombination-initiation double-strand break. Moreover, whereas the repetitive sequence had no effect on the frequency of single crossover, its presence strongly stimulated the formation of multiple crossovers. The combined data strongly suggest that numerous recombination events are restricted to the initiation side of the microsatellite as though progression of the strand exchange initiated at the ARG4 promoter locus was impaired by the repetitive sequence. This observation corroborates in vitro experiments that demonstrated that RecA-promoted strand exchange is inhibited by CA/GT dinucleotide tracts. Surprisingly, meiotic instability of the microsatellite was very high (>0.1 alterations per tetrad) in all the spores with parental and recombinant chromosomes.


A theoretical framework and competency-based approach to improving handoffs.
Once characterised by remarkable continuity of care by a familiar doctor, patient care today is delivered by multiple physicians with varying degrees of knowledge of the patient. Yet, few trainees learn the potential risks of these transitions and the strategies to improve patient care during handoffs. Little is known regarding the mechanisms by which handoffs affect patient care. Building on theoretical constructs from the social sciences and illustrated with a case study of the implementation of a night float service for the inpatient general medicine services at the University of Chicago, a conceptual framework is proposed to describe how handoffs affect both patients and physicians. Using this conceptual framework, recommendations are made for formal education based on the core competencies of communication and professionalism. Opportunities to educate trainees in acquiring these skills are described in the context of handoffs of patient care.


Chemiluminescence DNA biosensor based on dual-amplification of thrombin and thiocyanuric acid-gold nanoparticle network.
A sensitive DNA biosensor based on dual-amplification of thrombin and thiocyanuric acid-gold nanoparticle (TCA-AuNP) network is developed. First, the sandwich hybridization is formed by the capture probe immobilized on the surface of magnetic beads (MBs), the target DNA and the reporter probe loaded on PbS nanoparticles (PbS NPs). The PbS NPs contain two kinds of DNA sequences, one is the reporter probe complementary to the target DNA, and the other is the thrombin aptamer I. Through the specific recognition for thrombin, thrombin aptamer II labeled gold nanoparticles are linked to the sandwich complex, and further fabricate a network with TCA. AuNPs are released and dissolved into Au(3+), which catalyzes luminol chemiluminescence (CL) reaction. Due to the dual-amplification effects of thrombin-labeled PbS NPs and the TCA-AuNP network, a significant sensitivity enhancement of this DNA biosensor could be obtained, in the range of 2.0 x 10(-16) M to 3.5 x 10(-14) M, with a limit of detection (LOD) as low as 1.0 x 10(-16) M.


Asthma is more prevalent in elite swimming adolescents despite better mental and physical health.
An increased risk of developing asthma has been reported among swimmers exposed to chloramine in pool arenas. The aim of the present study was to compare the prevalence of asthma and respiratory symptoms among elite aspiring swimmers compared with age-matched controls with different degrees of physical activity. We also aimed to relate these findings to mental and psychosocial factors. One hundred and one elite swimmers and 1628 age-matched controls answered a questionnaire containing questions about respiratory symptoms, lifestyle factors, mental and physical well-being. The controls were divided into three different groups according to the degree of physical activity, no physical activity, recreational training and elite training. Swimmers reported significantly more asthma symptoms, with 36.6% having physician-diagnosed asthma, compared with 16.2% among the controls. Use of regular medication was more common (14.9% vs 8.0%) and more swimmers reported an exacerbation of their asthma during the previous 12 months (16.8%) vs (5.8%) for the controls. Despite an increased prevalence of asthma symptoms, the swimmers reported best physical performance and best mental and physical well-being. They also had a healthier lifestyle without smoking and low alcohol consumption.


miR-1260b inhibits periodontal bone loss by targeting ATF6β mediated regulation of ER stress.
The expression profiles of exosomal microRNAs (miRNAs) are regulated by the microenvironment, and appropriate priming with mesenchymal stem cells (MSCs) is one of the strategies to enhance the paracrine potency of MSCs. Our previous work demonstrated that exosomes from tumor necrosis factor (TNF)-α-primed human gingiva-derived MSCs (GMSCs) could be a therapeutic tool against periodontitis, and that TNFα-inducible exosomal miR-1260b is essential for the inhibition of alveolar bone loss. However, the precise molecular mechanism underlying miR-1260b-mediated inhibition of osteoclastogenesis is not yet fully understood. Here, we found that the activating transcription factor (ATF)-6β, a novel miR-1260b-targeting gene, is critical for the regulation of osteoclastogenesis under endoplasmic reticulum (ER) stress. An experimental periodontal mouse model demonstrated that induction of ER stress was accompanied by enhanced ATF6β expression, and local administration of miR-1260b and ATF6β siRNA using polyethylenimine nanoparticles (PEI-NPs) significantly suppressed the periodontal bone resorption. In periodontal ligament (PDL) cells, the ER stress inducer, tunicamycin, enhanced the expression of the receptor activator of NF-κB ligand (RANKL), while miR-1260b-mediated downregulation of ATF6β caused RANKL inhibition. Furthermore, the secretome from miR-1260b/ATF6β-axis-activated PDL cells inhibited osteoclastogenesis in human CD14+ peripheral blood-derived monocytes. These results indicate that the miR-1260b/ATF6β axis mediates the regulation of ER stress, which may be used as a novel therapeutic strategy to treat periodontal disease.


Pulsed radiofrequency V2 treatment and intranasal sphenopalatine ganglion block: a combination therapy for atypical trigeminal neuralgia.
Trigeminal neuralgia (TN) is a chronic condition affecting the fifth cranial nerve and resulting in sporadic intense burning and shock-like pain lasting for seconds to minutes that can be incapacitating to patients. Atypical TN includes additional features such as continuous pain and sensory disturbances in the area innervated by one or more branches of the trigeminal nerve. Documented cases of TN have dated back to the 18th century. Today, there are roughly 140,000 people suffering with this condition in the U.S.A. Conventional treatments for this disorder include medical management with nonconvulsants such as carbamazepine, which decrease the nerves response to peripheral stimulation. These agents have good initial pain relief, but relief rates fall off dramatically over the long-term. Recently, methadone has shown promise as a pharmacologic adjunct to patients with intractable neuropathic noncancer pain, including patients suffering from TN. Cases refractory to medical management can be treated with surgical microdecompression or minimally invasive procedures such as radiofrequency (RF) treatment. Pulsed RF (PRF) is a method gaining interest as it is delivered in pulses, allowing adequate time for dissipation of heat and energy resulting in less damage to surrounding structures. This case report describes the successful treatment of atypical V2 TN refractive to medical management requiring PRF treatment, a sphenopalatine block series, and low-dose methadone.


[Proteolytic lysosomal enzymes in ovarian cancer].
Activity of lysosomal proteinases cathepsins B and D was studied in normal tissues, malignant and benign ovary tumors, in blood sera and ascites fluid of patients with primary ovary cancer. The cathepsin B activity was 12-fold higher in tissues of ovary malignant tumors as compared with that of normal ovary and 6-fold higher -- as compared with tissues of benign tumors. Activation of the enzyme depended directly on the mass of malignant tumors and on the intensity of their penetration into surrounding tissues (uterus, urinary bladder, small pelvic fat) and spreading over peritoneum. Activity of cathepsin D was 2- and 2.6-fold higher in malignant ovary tumors as compared with normal tissue and benign tumors, respectively. The data obtained suggest that estimation of cathepsins B and D activities in bioptic material from ovary tumors might be useful for diagnosis of the disease.


Residue Y70 of the Nitrilase Cyanide Dihydratase from Bacillus pumilus Is Critical for Formation and Activity of the Spiral Oligomer.
Nitrilases pose attractive alternatives to the chemical hydrolysis of nitrile compounds. The activity of bacterial nitrilases towards substrate is intimately tied to the formation of large spiral-shaped oligomers. In the nitrilase CynD (cyanide dihydratase) from Bacillus pumilus, mutations in a predicted oligomeric surface region altered its oligomerization and reduced its activity. One mutant, CynD Y70C, retained uniform oligomer formation however it was inactive, unlike all other inactive mutants throughout that region all of which significantly perturbed oligomer formation. It was hypothesized that Y70 is playing an additional role necessary for CynD activity beyond influencing oligomerization. Here, we performed saturation mutagenesis at residue 70 and demonstrated that only tyrosine or phenylalanine is permissible for CynD activity. Furthermore, we show that other residues at this position are not only inactive, but have altered or disrupted oligomer conformations. These results suggest that Y70's essential role in activity is independent of its role in the formation of the spiral oligomer.


Electroacupuncture enhances resting-state functional connectivity between dorsal caudate and precuneus and decreases associated leptin levels in overweight/obese subjects.
Electroacupuncture (EA) is a safe and effective method for treating obesity. However, how it modulates reward-related brain activity/functional connectivity and gut hormones remains unclear. We employed resting-state functional magnetic resonance imaging (RS-fMRI) and resting-state functional connectivity (RSFC) to investigate EA induced changes in resting-state activity and RSFC in reward-related regions and its association with gut hormones in overweight/obese subjects who received real (n = 20) and Sham (n = 15) stimulation. Results showed reduced leptin levels was positively correlated with reduced body mass index (BMI) and negatively correlated with increased cognitive-control as measured with Three-Factor-Eating-Questionnaire (TFEQ). Significant time effects on RSFC between dorsal caudate (DC) and precuneus were due to significant increased RSFC strength in both EA and Sham groups. In addition, increased RSFC of DC-precuneus was negatively correlated with reduced BMI and leptin levels in the EA group. Mediation analysis showed that the relationship between increased DC-precuneus RSFC strength and reduced BMI was mediated by reduced leptin levels. These findings reflect the association between EA-induced brain reward-related RSFC and leptin levels, and decreased leptin levels mediated altered DC-precuneus RSFC strength and consequent weight-loss, suggesting the potential role of EA in reducing weight and appetite.


Differential expression of syndecan-1 mediates cationic nanoparticle toxicity in undifferentiated versus differentiated normal human bronchial epithelial cells.
Most in vitro toxicity studies on engineered nanomaterials (ENMs) use transformed rather than primary cells for logistical reasons. However, primary cells may provide a more appropriate connection to in vivo toxicity because these cells maintain their phenotypic fidelity and are also capable of differentiating into lineages that may be differently affected by potentially hazardous ENMs. Few studies to date have focused on the role of cellular differentiation in determining ENM toxicity. We compared the response of undifferentiated and differentiated primary human bronchial epithelial (NHBE) cells to cationic mesoporous silica nanoparticles (MSNPs) that are coated with polyethyleneimine (PEI) since this polymer is known to exert differential cytotoxicity depending on its molecular weight and cationic density. The attachment of cationic PEI polymers to the MSNP surface was used to assess these materials' toxicological potential in undifferentiated and differentiated human bronchial epithelial cells, using a multiparametric assay that screens for an integrated set of sublethal and lethal response outcomes. MSNPs coated with high molecular weight (10 and 25 kD) polymers were more toxic in differentiated cells than particles coated with shorter length polymers. The increased susceptibility of the differentiated cells is in agreement with more abundant expression of a proteoglycan, syndecan-1, which contains copious heparin sulfate side chains. Pretreatment with heparinase to remove the negatively charged sulfates decreased MSNP-PEI binding to the cell surface and lowered the cytotoxic potential of the cationic particles. These data demonstrate the importance of studying cellular differentiation as an important variable in the response of primary cells to toxic ENM properties.


The koniocellular pathway in primate vision.
A neurochemically distinct population of koniocellular (K) neurons makes up a third functional channel in primate lateral geniculate nucleus. As part of a general pattern, K neurons form robust layers through the full representation of the visual hemifield. Similar in physiology and connectivity to W cells in cat lateral geniculate nucleus, K cells form three pairs of layers in macaques. The middle pair relays input from short-wavelength cones to the cytochrome-oxidase blobs of primay visual cortex (V1), the dorsal-most pair relays low-acuity visual information to layer I of V1, and the ventral-most pair appears closely tied to the function of the superior colliculus. Throughout each K layer are neurons that innervate extrastriate cortex and that are likely to sustain some visual behaviors in the absence of V1. These data show that several pathways exist from retina to V1 that are likely to process different aspects of the visual scene along lines that may remain parallel well into V1.


Xylan as limiting factor in enzymatic hydrolysis of nanocellulose.
The role of xylan as a limiting factor in the enzymatic hydrolysis of cellulose was studied by hydrolysing nanocellulose samples prepared by mechanical fibrillation of birch pulp with varying xylan content. Analyzing the nanocelluloses and their hydrolysis residues with dynamic FT-IR spectroscopy revealed that a certain fraction of xylan remained tightly attached to cellulose fibrils despite partial hydrolysis of xylan with xylanase prior to pulp fibrillation and that this fraction remained in the structure during the hydrolysis of nanocellulose with cellulase mixture as well. Thus, a loosely bound fraction of xylan was predicted to have been more likely removed by purified xylanase. The presence of loosely bound xylan seemed to limit the hydrolysis of crystalline cellulose, indicated by an increase in cellulose crystallinity and by preserved crystal width measured with wide-angle X-ray scattering. Removing loosely bound xylan led to a proportional hydrolysis of xylan and cellulose with the cellulase mixture.


Microalgal Peloids for Cosmetic and Wellness Uses.
Peloids have been used for therapeutic purposes since time immemorial, mainly in the treatment of locomotor system pathologies and dermatology. Their effects are attributed to their components, i.e., to the properties and action of mineral waters, clays, and their biological fraction, which may be made up of microalgae, cyanobacteria, and other organisms present in water and clays. There are many studies on the therapeutic use of peloids made with microalgae/cyanobacteria, but very little research has been done on dermocosmetic applications. Such research demonstrates their potential as soothing, regenerating, antioxidant, anti-inflammatory, and antimicrobial agents. In this work, a method for the manufacture of a dermocosmetic peloid is presented based on the experience of the authors and existing publications, with indications for its characterization and study of its efficacy.


The impact of UV-C irradiation on spoilage microorganisms and colour of orange juice.
The effect of UV-C irradiation on inactivation of spoilage microorganisms and colour of freshly squeezed orange juice were investigated. Orange juice samples were intentionally fermented in order to increase the natural microflora which were mostly composed of yeasts and then exposed to UV-C irradiation at an intensity level of 1.32 mW/cm(2) and sample depth of 0.153 cm for several exposure times by using a collimated beam apparatus. Applied UV dose was in the range of 0 and 108.42 mJ/cm(2). Resistance of yeast to UV light and existence of suspended particles limited the effectiveness of the process. Survival data obtained for yeasts was either described by the Weibull or traditional first-order model and goodness-of-fit of these models was investigated. Weibull model produced a better fit to the data with higher adjusted determination coefficient (R(2) adj) and lower mean square error (MSE) values which were 0.99 and 0.003, respectively. Time and UV dose of first decimal reduction were obtained as 5.7 min and 31 mJ/cm(2), respectively. The data suggests that biodosimetric studies performed by using inoculated microorganisms for assesment of the efficiency of UV irradiation treatment in the shelf life extension of juices must be carefully evaluated. UV-C irradiation had no influence on the colour of orange juice.


Structural and evolutionary classification of Type II restriction enzymes based on theoretical and experimental analyses.
For a very long time, Type II restriction enzymes (REases) have been a paradigm of ORFans: proteins with no detectable similarity to each other and to any other protein in the database, despite common cellular and biochemical function. Crystallographic analyses published until January 2008 provided high-resolution structures for only 28 of 1637 Type II REase sequences available in the Restriction Enzyme database (REBASE). Among these structures, all but two possess catalytic domains with the common PD-(D/E)XK nuclease fold. Two structures are unrelated to the others: R.BfiI exhibits the phospholipase D (PLD) fold, while R.PabI has a new fold termed 'half-pipe'. Thus far, bioinformatic studies supported by site-directed mutagenesis have extended the number of tentatively assigned REase folds to five (now including also GIY-YIG and HNH folds identified earlier in homing endonucleases) and provided structural predictions for dozens of REase sequences without experimentally solved structures. Here, we present a comprehensive study of all Type II REase sequences available in REBASE together with their homologs detectable in the nonredundant and environmental samples databases at the NCBI. We present the summary and critical evaluation of structural assignments and predictions reported earlier, new classification of all REase sequences into families, domain architecture analysis and new predictions of three-dimensional folds. Among 289 experimentally characterized (not putative) Type II REases, whose apparently full-length sequences are available in REBASE, we assign 199 (69%) to contain the PD-(D/E)XK domain. The HNH domain is the second most common, with 24 (8%) members. When putative REases are taken into account, the fraction of PD-(D/E)XK and HNH folds changes to 48% and 30%, respectively. Fifty-six characterized (and 521 predicted) REases remain unassigned to any of the five REase folds identified so far, and may exhibit new architectures. These enzymes are proposed as the most interesting targets for structure determination by high-resolution experimental methods. Our analysis provides the first comprehensive map of sequence-structure relationships among Type II REases and will help to focus the efforts of structural and functional genomics of this large and biotechnologically important class of enzymes.


Sox11 is expressed in early progenitor human multipotent stromal cells and decreases with extensive expansion of the cells.
There has been considerable interest in developing new therapies with adult multipotent progenitor stromal cells or mesenchymal stem cells (MSCs) in organ replacement and repair. To be effectively seeded into scaffolds for therapy, large numbers of cells are needed, but concerns remain regarding their chromatin stability in long-term culture. We therefore expanded four donors of human MSCs (hMSCs) from bone marrow aspirates with a protocol that maintains the cells at low density. MSCs initially proliferated at average doubling times of 24 h and then gradually reached senescence after 8-15 passages (33-55 population doublings) without evidence of immortalization. Comparative genomic hybridization assays of two preparations revealed no abnormalities through 33 population doublings. One preparation had a small amplification of unknown significance in chromosome 7 (7q21:11) after 55 population doublings. Microarray assays demonstrated progressive changes in the transcriptome of the cells. However, the transcriptomes clustered more closely over time within a single passage, rather than with passage number, indicating a partial reversibility of the patterns of gene expression. One of the largest changes was a decrease in mRNA for Sox11, a transcription factor previously identified in neural progenitor cells. Knockdown of Sox11 with siRNA decreased the proliferation and osteogenic differentiation potential of hMSCs. The results suggested that assays for Sox11 may provide a biomarker for early progenitor hMSCs.


The longitudinal elderly person shadowing program: outcomes from an interprofessional senior partner mentoring program.
The University of Saskatchewan's Longitudinal Elderly Person Shadowing (LEPS) is an interprofessional senior mentors program (SMP) where teams of undergraduate students in their first year of medicine, pharmacy, and physiotherapy; 2nd year of nutrition; 3rd year nursing; and 4th year social work partner with community-dwelling older adults. Existing literature on SMPs provides little information on the sustainability of attitudinal changes toward older adults or changes in interprofessional attitudes. LEPS students completed Polizzi's Aging Semantic Differential and the Interdisciplinary Education Perception Scale. Perceptions of older men and women improved significantly and changes were sustained after one year. However, few changes were seen in interprofessional attitudes.


Tracing the evolutionary history of Drosophila regulatory regions with models that identify transcription factor binding sites.
Much of evolutionary change is mediated at the level of gene expression, yet our understanding of regulatory evolution remains unsatisfying. In light of recent data indicating that transcription factor binding sites undergo substantial turnover between species, we attempt to quantify the process of binding site turnover in regulatory regions of well-studied genes controlling embryonic patterning in Drosophila. We examine polymorphism and divergence data in Drosophila melanogaster and four related species from regulatory regions of five early development genes for which functional binding sites have been identified. This analysis reveals that Drosophila regulatory regions exhibit patterns of variation consistent with functional constraint. We develop a novel approach to binding site prediction which we use to characterize the process of binding site divergence in regulatory regions. This method uses sets of known binding sites to construct a model that predicts transcription factor specificity and bootstrap sampling to derive significance levels. This approach allows appropriate significance levels to be determined even in the face of skewed base composition in the background sequence. Using this approach, we show that, although functional elements exhibit conservation of sequence, there is substantial potential to gain new functional elements within the regulatory regions. Our results show that application of models that predict transcription factor binding sites can yield insights into the process and dynamics of binding site evolution within regulatory regions.


Incidence and risk factors for early wound complications after spinal arthrodesis in children: analysis of 30-day follow-up data from the ACS-NSQIP.
Retrospective review of prospectively collected data. To determine the incidence and risk factors for 30-day wound complication after spinal arthrodesis in pediatric patients. Although multiple prior studies have reported on wound complications in pediatric spine, the majority have been single-center retrospective series. The National Surgical Quality Improvement Program (NSQIP) employs on-site personnel to prospectively collect 30-day morbidity data from 50 pediatric centers. Year 2012 was the first year of enrollment, and 1915 cases with thoracic or lumbar spinal fusion were included. Patients were divided into cohorts of those with and without a wound complication, with univariate and multivariate analyses used to identify risk factors. A P value of less than 0.05 was considered significant. Wound complications occurred in 67 patients (3.5%). The incidence was significantly higher in patients with congenital (4.35%) or neuromuscular (4.67%) diagnoses, as opposed to idiopathic (2.7%) or infantile (1.61%). Procedures with fusions extending to the pelvis (9.91%) or an osteotomy (4.99%) were associated with higher risk. Longer hospital lengths of stay, increased operative time, increased patient body mass index, and patients with cardiac, gastrointestinal, neurological, or pulmonary comorbidities were also associated with a higher risk. In the multivariate analysis, a body mass index of more than 30 kg/m2, patients with cardiac risk factors, and fusions extending to the pelvis were independent risk factors. Data from this large prospective multicenter study confirm that the incidence of early wound complications in pediatric spine surgery is low. Patients with a fusion extending to the pelvis, obese patients, and patients with significant cardiac conditions were independently associated with higher risk for this complication. These data should be useful for patients' counseling and for preoperative risk stratification. Interventions for minimizing wound complication risk may be most applicable to the high-risk groups identified here. 2.


Protection from respiratory syncytial virus infection in cotton rats by passive transfer of monoclonal antibodies.
The effects of passive administration of neutralizing monoclonal antibodies (MAB) to respiratory syncytial virus glycoproteins (GP90 and VP70) was evaluated in cotton rats challenged with respiratory syncytial virus. Animals injected with MAB to VP70 had lower mean viral titers in lung tissues than did controls (log10 2.5 versus 5.4 PFU/g; P less than 0.001), as did cotton rats given MAB to GP90 (log10 2.1 versus 5.0 PFU/g; P less than 0.001). Fifty percent of animals given either MAB had no detectable virus in lung tissues, whereas virus was detected in the lungs of all controls. Virus growth in nasal turbinates was decreased but not eliminated in recipients of either MAB.


Rapid Quantification and Validation of Lipid Concentrations within Liposomes.
Quantification of the lipid content in liposomal adjuvants for subunit vaccine formulation is of extreme importance, since this concentration impacts both efficacy and stability. In this paper, we outline a high performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) method that allows for the rapid and simultaneous quantification of lipid concentrations within liposomal systems prepared by three liposomal manufacturing techniques (lipid film hydration, high shear mixing, and microfluidics). The ELSD system was used to quantify four lipids: 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), cholesterol, dimethyldioctadecylammonium (DDA) bromide, and ᴅ-(+)-trehalose 6,6'-dibehenate (TDB). The developed method offers rapidity, high sensitivity, direct linearity, and a good consistency on the responses (R² > 0.993 for the four lipids tested). The corresponding limit of detection (LOD) and limit of quantification (LOQ) were 0.11 and 0.36 mg/mL (DMPC), 0.02 and 0.80 mg/mL (cholesterol), 0.06 and 0.20 mg/mL (DDA), and 0.05 and 0.16 mg/mL (TDB), respectively. HPLC-ELSD was shown to be a rapid and effective method for the quantification of lipids within liposome formulations without the need for lipid extraction processes.


Polo-like kinase 1 promotes sepsis-induced myocardial dysfunction.
Sepsis-induced myocardial dysfunction (SIMD) is the main cause of mortality in sepsis. In this study, we identified Polo-like kinase 1 (Plk-1) is a promoter of SIMD. Plk-1 expression was increased in lipopolysaccharide (LPS)-treated mouse hearts and neonatal rat cardiomyocytes (NRCMs). Inhibition of Plk-1 either by heterozygous deletion of Plk-1 or Plk-1 inhibitor BI 6727 alleviated LPS-induced myocardial injury, inflammation, cardiac dysfunction, and thereby improved the survival of LPS-treated mice. Plk-1 was identified as a kinase of inhibitor of kappa B kinase alpha (IKKα). Plk-1 inhibition impeded NF-κB signal pathway activation in LPS-treated mouse hearts and NRCMs. Augmented Plk-1 is thus essential for the development of SIMD and is a druggable target for SIMD.


Towards building a chromosome segregation machine.
All organisms, from bacteria to humans, face the daunting task of replicating, packaging and segregating up to two metres (about 6 x 10(9) base pairs) of DNA when each cell divides. This task is carried out up to a trillion times during the development of a human from a single fertilized cell. The strategy by which DNA is replicated is now well understood. But when it comes to packaging and segregating a genome, the mechanisms are only beginning to be understood and are often as variable as the organisms in which they are studied.


Association between soil heavy metals and fatty liver disease in men in Taiwan: a cross sectional study.
Metabolic factors are major risk factors for non-alcoholic fatty liver disease although other factors may also contribute to development of fatty liver disease. We explored the association between exposure to soil heavy metals and prevalence of fatty liver disease. We retrospectively analysed data from patients diagnosed with fatty liver disease in 2014 at the Health Evaluation Centre of Chang-Hua Christian Hospital (n=1137). We used residency data provided in the records of the Health Evaluation Centre and data for soil metal concentrations from a nationwide survey conducted by the Environmental Protection Administration of Taiwan. We studied the correlations between the severity of fatty liver disease and concentrations of soil heavy metals (arsenic, mercury, cadmium, chromium, copper, nickel, lead and zinc). The prevalence of moderate to severe fatty liver disease in our study was 26.5%. Using univariate and multivariate analysis, we demonstrated that the presence of soil heavy metals was a significant risk factor for fatty liver disease in men (OR 1.83, 95% CI 1.161 to 2.899, p=0.009). With stratification by body mass index (BMI) and gender, lean men with a BMI <24 kg/m2 were the most susceptible to soil heavy metals (OR 5.059, 95% CI 1.628 to 15.728, p<0.05). Our study suggested a significant association between exposure to soil heavy metals and fatty liver disease in lean men.


Does the EcoRI polymorphism in the human apolipoprotein B gene affect the binding of low density lipoprotein to the low density lipoprotein receptor?
In human populations, there is an association between coronary artery disease and a polymorphism in the apolipoprotein B (apo B) gene detected with the enzyme EcoRI. This polymorphism gives rise to two apo B alleles, one (E+) encoding glutamic acid and the other (E-) encoding lysine at position 4,154 in apo B-100, the protein of low density lipoprotein (LDL). We have tested the hypothesis that this amino acid substitution indirectly influences proneness to coronary artery disease by affecting the binding of LDL to LDL receptors. The receptor-binding affinities of LDLs from eight pairs of subjects with genotypes E+/+ and E-/- who were matched for other apo B genotypes were determined in vitro. There was no significant difference between the binding affinities of LDLs from the two groups of subjects. Our results strongly suggest that the amino acid at position 4,154 does not influence the function of the receptor-binding domain in apo B-100 and that the association between coronary artery disease and the EcoRI polymorphism is not mediated by an effect of the polymorphism on serum LDL concentration. In view of our findings, it would be of interest to examine the effect of the amino acid substitution on the binding of LDL to arterial proteoglycans and on the oxidizability of LDL by cells in culture.


Ventricular fibrillation and rhabdomyolysis after administration of succinylcholine.
Succinylcholine is a depolarising muscle relaxant. Because of its quick onset of action, it is particularly used in situations which require urgent intubation. However, there have been several reports of cardiac arrest after administration of succinylcholine. We describe the case of a young woman who developed ventricular fibrillation and rhabdomyolysis following succinylcholine administration. Possible mechanisms and treatment are discussed.


A2A adenosine receptor-driven cAMP signaling in olfactory bulb astrocytes is unaffected in experimental autoimmune encephalomyelitis.
The cyclic nucleotide cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger, which is known to play an important anti-inflammatory role. Astrocytes in the central nervous system (CNS) can modulate inflammation but little is known about the significance of cAMP in their function. We investigated cAMP dynamics in mouse olfactory bulb astrocytes in brain slices prepared from healthy and experimental autoimmune encephalomyelitis (EAE) mice. The purinergic receptor ligands adenosine and adenosine triphosphate (ATP) both induced transient increases in cAMP in astrocytes expressing the genetically encoded cAMP sensor Flamindo2. The A2A receptor antagonist ZM241385 inhibited the responses. Similar transient increases in astrocytic cAMP occurred when olfactory receptor neurons were stimulated electrically, resulting in ATP release from the stimulated axons that increased cAMP, again via A2A receptors. Notably, A2A-mediated responses to ATP and adenosine were not different in EAE mice as compared to healthy mice. Our results indicate that ATP, synaptically released by afferent axons in the olfactory bulb, is degraded to adenosine that acts on A2A receptors in astrocytes, thereby increasing the cytosolic cAMP concentration. However, this pathway is not altered in the olfactory bulb of EAE mice.


Vetiver grass (Chrysopogon zizanioides) is capable of removing insensitive high explosives from munition industry wastewater.
Synthetic organic explosive compounds in the wastewater stream of industrial munition facilities are subject to regulatory permits and require pretreatment prior to discharge. Munition industries are currently focused on developing insensitive high explosives (IHEs) such as dinitroanisole (DNAN), nitroguanidine (NQ), and 1,2,4-triazol-3-one (NTO), to replace conventional munitions such as trinitrotoluene (TNT) and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). IHEs are typically more soluble than conventional explosives, and their production generates waste streams with high nitrate (N) concentrations. Several chemical remediation studies have attempted to degrade the explosive compounds within waste streams with limited success. Phytoremediation is a relatively new application for the remediation of munition industry wastewater, which is both environmentally and economically sustainable. Vetiver grass (Chrysopogon zizanioides), with its massive and dense root system and ability to grow in harsh environments, has been observed to remove many chemicals from soil and water, including nutrients and TNT. The objective of this study was to evaluate the phytoremediation potential of vetiver in removing explosive compounds and N from wastewater effluents generated in an industrial munition facility. Results show that the removal efficiency of vetiver was a factor of the initial concentration. Successive batches of vetiver removed DNAN, NQ, and RDX by 96, 79 and 100%, respectively. More than 95% of N was removed by four successive batches of vetiver grass. A major portion of NQ and RDX was translocated from root to shoot. LC-MS analysis showed the presence of transformation products of RDX, HMX (1,3,5,7-Tetranitro-1,3,5,7-tetrazocane) and DNAN in vetiver root and shoot.


Detection of Zaire ebolavirus in swine: Assay development and optimization.
Ebolaviruses (family Filoviridae, order Mononegavirales) cause often fatal, haemorrhagic fever in primates including humans. Pigs have been identified as a species susceptible to Reston ebolavirus (RESTV) infection, with indicated transmission to humans in the Philippines; however, their role during Ebola outbreaks in Africa needs to be clarified. To perform surveillance studies, detection of ebolavirus requires a prerequisite validation of viral RNA and antibody detection methods in swine samples. These diagnostic tests also need to be suitable for deployment to low-level containment laboratories. In this study, we developed a set of tests for detection of antibodies against Zaire ebolavirus (EBOV) in swine. Recombinant EBOV nucleoprotein was produced using a baculovirus expression system for indirect ELISA development. Evaluation of this assay was performed using laboratory and field samples, achieving a diagnostic specificity of 99%. Importantly, the indirect ELISA was able to detect antibodies to EBOV at 7 dpi, 3 days earlier than virus neutralization tests (VNT). The format of the VNT in this work was modified to a microtitre plaque reduction neutralization assay (miPRNT) complemented with immunostaining to provide a more rapid and highly specific assay. Finally, a confirmatory immunoblot assay was generated to supplement the indirect ELISA results.


Lactate-induced translocation of GLUT1 and GLUT4 is not mediated by the phosphatidyl-inositol-3-kinase pathway in the rat heart.
We have determined the effect of lactate on the translocation of GLUT1 and GLUT4 and on the myocardial uptake and phosphorylation of the glucose analogues 2-deoxy-D-glucose (DG) and 2-18F-fluoro-2-deoxy-D-glucose (18FDG). The involvement of phosphatidyl-inositol-3-kinase (PI3K) in this translocation was determined using wortmannin. Hearts from fed and fasted male Wistar rats were perfused in the presence of 11 mM glucose +/- 10 mM lactate for two hours and the distribution of glucose transporters was determined using Western blot techniques. Two other groups of hearts from fed animals were perfused in the presence of 11 mM glucose +/- 10 mM lactate for two hours followed by perfusion for a further 30 minutes in the presence of 4 mM 2-deoxy-D-glucose. Using 31P NMR spectroscopy, the accumulation of 2-deoxy-D-glucose-6-phosphate (DG6P) was monitored over time. Another group of hearts from fed animals was initially perfused in the presence of 11 mM glucose for 100 minutes and then the perfusate was changed to 11 mM glucose + 10 mM lactate for a further 120 minutes. Using PET, the accumulation of 2-18F-fluoro-deoxy-D-glucose-6-phosphate (18FDG6P) was monitored throughout the whole protocol. Lactate induced the translocation of both GLUT1 and GLUT4 to the plasma membrane (from 67 +/- 1% to 82 +/- 2% and from 16 +/- 1% to 28 +/- 2%, respectively (P < 0.05)) in hearts from fed animals; similar translocations were observed in hearts from fasted animals. Wortmannin did not inhibit the translocation of either GLUT1 or GLUT4. Glucose transporter translocation was accompanied by a significant inhibition of DG6P accumulation (4.24 +/- 0.68 vs. 1.50 +/- 0.38; P < 0.001) and a decrease in the rate of 18FDG6P accumulation. In conclusion, lactate causes translocation of GLUT1 and GLUT4 to the plasma membrane, via a non-PI3K-mediated pathway. Despite this externalisation of the GLUT transporters, a marked decrease in the accumulation of both DG6P and 18FDG6P was observed.


Idiopathic Sialolithiasis: Scalpel Versus Current Trends in Management.
Idiopathic sialolithiasis is one of the most common affliction of the salivary glands with the submandibular gland most frequently involved. The article discusses the occurrence and incidence of this condition with a review of different diagnostic and treatment modalities. In light of several advances to diagnose and treat sialolithiasis, a simple sialolithotomy for idiopathic submandibular gland sialolithiasis may prove to be a preferred treatment for selected patients as it remains a cost-effective and simple out-patient department procedure with minimal/no complications and a highly satisfactory outcome. For stones slightly proximal in the Wharton duct, a "dual" approach of milking the gland to bring the stone more distally followed by a sialolithotomy with a scalpel proves to be a quick and effective procedure.


Intralesional chemotherapy for nonmelanoma skin cancer: a practical review.
Intralesional chemotherapy for nonmelanoma skin cancer has existed for more than 5 decades. However, it is used so infrequently that recent consensus guidelines for the treatment of basal cell and squamous cell carcinoma do not include intralesional chemotherapy. Barriers to the use of intralesional chemotherapy include the off-label use of these agents, absence of therapeutic guidelines, a relatively small number of patients treated, and a lack of large, well-designed trials with long-term follow-up. Surgical intervention remains the gold standard for the treatment of nonmelanoma skin cancer; however, intralesional chemotherapy remains an option for well-selected patients who cannot or will not undergo surgery. The objectives of this article are to determine response rates and suggest reasonable treatment guidelines for the treatment of squamous cell carcinoma, keratoacanthoma, and basal cell carcinoma with the most widely available intralesional agents (methotrexate, 5-fluorouracil, bleomycin, and interferon).


Resistant starch manipulated hyperglycemia/hyperlipidemia and related genes expression in diabetic rats.
The effect of resistant starch (RS) administration on biological parameters including blood glucose, lipids composition and oxidative stress of type 2 diabetic rats was investigated. The results showed blood glucose level, total cholesterol and triglycerides concentrations significantly reduced, and high-density lipoprotein cholesterol concentration was doubly increased in the rats of RS administration group compared to model control group (P<0.01). The analyses of genes involved in glucose and lipid metabolism pathways demonstrated that the expression levels of lipid oxidation gene Acox1, glycogen synthesis genes, GS2 and GYG1, and insulin-induced genes, Insig-1 and Insig-2, were significantly up-regulated (P<0.01). In contrast, fatty acids and triglycerides synthesis and metabolism-related gene SREBP-1, fatty acid synthesis gene Fads1 and gluconeogenesis gene G6PC1 were greatly down-regulated. The mechanism study shows that the lowering of blood glucose level in diabetic rats by feeding RS is regulated through promoting glycogen synthesis and inhibiting gluconeogenesis, and the increased lipid metabolism is modulated through promoting lipid oxidation and cholesterol homeostasis. Our study revealed for the first time that the regulation of hepatic genes expression involved in glucose and lipids metabolisms in diabetic rats could be achieved even at a moderate level of RS consumption.


An Outbreak of Brucellosis: An Adult and Pediatric Case Series.
Brucellosis is recognized as a neglected zoonotic disease and a major public health threat. The purpose of this study was to characterize epidemiological risk factors and healthcare utilization and compare clinical aspects of disease among adult and pediatric cases in North Texas. A retrospective chart review of electronic medical records was completed at 3 large tertiary centers-Parkland Health and Hospital System, Clements University Hospital, and Children's Medical Center-between January 1, 2007 and June 1, 2017. Demographic, clinical, and laboratory variables were collected. Cases were defined as confirmed or probable. Twenty-eight cases of brucellosis were identified: 26 confirmed (9 children, 17 adults) and 2 probable cases (1 child, 1 adult). Half (n = 14) were diagnosed in 2016 during an outbreak in Dallas County. Risk factors associated with infection were consumption of unpasteurized cheese (71%), recent travel (54%), close contact to a confirmed human brucellosis case (36%), and exposure to animals (11%). Median days of symptoms was 10 and 16 for children and adults, respectively. The majority (79%) of patients visited the emergency department before diagnosis and 93% were hospitalized. Fever was the most common symptom in children (80%) and adults (100%). Hepatitis (75% of children) and anemia (82% of adults) were the most common laboratory abnormalities. The most common complication in children was splenic lesions (40%), and the most common complication in adults was hepato/splenomegaly (39%). The diagnosis of Brucella infection requires a high index of suspicion and should be considered in patients presenting with a febrile illness and a compatible exposure history.


Tissue-type plasminogen activator of colonic mucosa in ulcerative colitis. Evidence of endothelium-derived fibrinolytic activation.
Microvascular endothelial alterations are thought to be a crucial step for development of hemorrhagic changes in various pathological states. In this study, we determined the activity and amount of tissue-type plasminogen activator (t-PA) in the biopsy specimens from sigmoid colon of patients with ulcerative colitis to evaluate endothelial alterations and vascular changes of permeability. The results of this investigation revealed that mucosal amount of t-PA in the active stage of ulcerative colitis was two- to threefold higher than in healthy controls, while t-PA levels in plasma samples showed no remarkable differences among the groups. Increased t-PA activity appeared to correlate well to the degree of inflammation of colonic mucosa, and t-PA amount was still increased in the inactive stage. The present study indicates that t-PA determination in colonic biopsy specimens may be useful for the evaluation of clinical activity of ulcerative colitis in terms of the mucosal microvascular endothelial changes.


On the sensitivity of alginate rheology to composition.
The linear response of alginate-phenyl boronic acid (Alg-PBA) esters shows a universal, composition-independent viscoelastic fluid-like behaviour. Reversible association of alginates governs their rheology at all compositions (viz. at all alginate concentrations and solution pH). However, their high strain behaviour is very sensitive to composition. Tuning composition affords liquids that neck to form filaments capable of being drawn to large elongations without failure. We interpret our data by invoking strain-dependent association and dissociation rates for the alginates. High association rates at high strain result in materials with viscoelastic liquid like behaviour.


A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency.
Chronic cerebrospinal venous insufficiency (CCSVI) is characterized by combined stenoses of the principal pathways of extracranial venous drainage, including the internal jugular veins (IJVs) and the azygous (AZY) vein, with development of collateral circles and insufficient drainage shown by increased mean transit time in cerebral magnetic resonance (MR) perfusion studies. CCSVI is strongly associated with multiple sclerosis (MS). This study evaluated the safety of CCSVI endovascular treatment and its influence on the clinical outcome of the associated MS. Sixty-five consecutive patients with CCSVI, subdivided by MS clinical course into 35 with relapsing remitting (RR), 20 with secondary progressive (SP), and 10 with primary progressive (PP) MS, underwent percutaneous transluminal angioplasty (PTA). Mean follow-up was 18 months. Vascular outcome measures were postoperative complications, venous pressure, and patency rate. Neurologic outcome measures were cognitive and motor function assessment, rate of MS relapse, rate of MR active positive-enhanced gadolinium MS lesions (Gad+), and quality of life (QOL) MS questionnaire. Outpatient endovascular treatment of CCSVI was feasible, with a minor and negligible complication rate. Postoperative venous pressure was significantly lower in the IJVs and AZY (P < .001). The risk of restenosis was higher in the IJVs compared with the AZY (patency rate: IJV, 53%; AZY, 96%; odds ratio, 16; 95% confidence interval, 3.5-72.5; P < .0001). CCSVI endovascular treatment significantly improved MS clinical outcome measures, especially in the RR group: the rate of relapse-free patients changed from 27% to 50% postoperatively (P < .001) and of MR Gad+ lesions from 50% to 12% (P < .0001). The Multiple Sclerosis Functional Composite at 1 year improved significantly in RR patients (P < .008) but not in PP or SP. Physical QOL improved significantly in RR (P < .01) and in PP patients (P < .03), with a positive trend in SP (P < .08). Mental QOL showed significant improvement in RR (P < .003) and in PP (P < .01), but not in SP. PTA of venous strictures in patients with CCSVI is safe, and especially in patients with RR, the clinical course positively influenced clinical and QOL parameters of the associated MS compared with the preoperative assessment. Restenosis rates are elevated in the IJVs but very promising in the AZY, suggesting the need to improve endovascular techniques in the former. The results of this pilot study warrant a subsequent randomized control study.


Corneal endothelium in viral induced anterior uveitis. Ultrastructural changes following canine adenovirus type 1 infection.
Dogs inoculated intravenously with attenuated canine adenovirus type 1 developed anterior segment inflammation and corneal edema. During the stage of mild anterior uveitis, virus was isolated from the aquious fluid, and by electron microscopy, viral replication was found to occur in corneal endothelial cells. Later, at the stage of severe anterior uveitis with corneal edema, virus was not isolated from the aqueous fluid and cells containing intranuclear (replicating) virus were not found. At this stage, many inflammatory cells had infiltrated the anterior chamber and contained numerous membrane-bound viral aggregates (viral-antibody complexes). Phagocytized viral-antibody complexes were present in the areas of most prominent endothelial cell destruction. Peripheral to the principal lesion sites, inflammatory cells had dissected the endothelium from Descemet membrane. After recovery from the disease, an intact endothelial cell layer was present.


Public health and social supervision issues within public administration of ukrainian territories in the late 8th- early 9th centuries.
Introduction: The public health system modernization history is based upon the progress in state country administration and administration of healthcare within the sectorwide approach. The WHO European Bureau pays much attention to the National Health Service systems development while implementing their basic policies. The Ukrainian state health service management was founded basing on the regulatory field of the Russian Empire, using the European healthcare promotion experience. Aim: of the article is the analysis of the regulatory field of police and amenity authorities of the Russian Empire and Ukraine within the medical and social service in the 18th-19th centuries. Materials and methods: The structure of the article corresponds to the problem city and chronology principles, using the following methods and techniques of scientific learning: the systemic, historic, regulatory comparative, logical and structural-functional analysis of the studied medical-legal phenomena. The study sources are the scientific publications, collections of laws and executive orders of the Russian Empire and Ukraine in the 18th-19th centuries. Review: As a result of the performed work it can be determined were the main directions of the police competence in late 18th- early 19th centuries. Conclusion: Preserving health, treatment of the ill and injured, management of medical and social service of those in need, holding various preventive activities and supporting safe environment and regulating the safety of food were the main directions of the police competence in late 18th- early 19th centuries.


External and circadian inputs modulate synaptic protein expression in the visual system of Drosophila melanogaster.
In the visual system of Drosophila melanogaster the retina photoreceptors form tetrad synapses with the first order interneurons, amacrine cells and glial cells in the first optic neuropil (lamina), in order to transmit photic and visual information to the brain. Using the specific antibodies against synaptic proteins; Bruchpilot (BRP), Synapsin (SYN), and Disc Large (DLG), the synapses in the distal lamina were specifically labeled. Then their abundance was measured as immunofluorescence intensity in flies held in light/dark (LD 12:12), constant darkness (DD), and after locomotor and light stimulation. Moreover, the levels of proteins (SYN and DLG), and mRNAs of the brp, syn, and dlg genes, were measured in the fly's head and brain, respectively. In the head we did not detect SYN and DLG oscillations. We found, however, that in the lamina, DLG oscillates in LD 12:12 and DD but SYN cycles only in DD. The abundance of all synaptic proteins was also changed in the lamina after locomotor and light stimulation. One hour locomotor stimulations at different time points in LD 12:12 affected the pattern of the daily rhythm of synaptic proteins. In turn, light stimulations in DD increased the level of all proteins studied. In the case of SYN, however, this effect was observed only after a short light pulse (15 min). In contrast to proteins studied in the lamina, the mRNA of brp, syn, and dlg genes in the brain was not cycling in LD 12:12 and DD, except the mRNA of dlg in LD 12:12. Our earlier results and obtained in the present study showed that the abundance of BRP, SYN and DLG in the distal lamina, at the tetrad synapses, is regulated by light and a circadian clock while locomotor stimulation affects their daily pattern of expression. The observed changes in the level of synaptic markers reflect the circadian plasticity of tetrad synapses regulated by the circadian clock and external inputs, both specific and unspecific for the visual system.


Trends in Prehospital Analgesia Administration by US Forces From 2007 Through 2016.
Tactical Combat Casualty Care (TCCC) guidelines regarding prehospital analgesia agents have evolved. The guidelines stopped recommending intramuscular (IM) morphine in 1996, recommending only intravenous (IV) routes. In 2006, the guidelines recommended oral transmucosal fentanyl citrate (OTFC), and in 2012 it added ketamine via all routes. It remains unclear to what extent prehospital analgesia administered on the battlefield adheres to these guidelines. We seek to describe trends in analgesia administration patterns on the battlefield during 2007-2016. This is a secondary analysis of a Department of Defense Trauma Registry data set from January 2007 to August 2016. Within that group, we searched for subjects who received IM morphine, IV morphine, OTFC, parenteral fentanyl, or ketamine (all routes). Our predefined ED search codes captured 28,222 subjects during the study period. Of these, 594 (2.1%) received IM morphine; 3,765 (13.3%) received IV morphine; 589 (2.1%) received OTFC; and 1,510 (5.4%) subjects received ketamine. Annual rates of administration of IM morphine were relatively stable during the study period, while those for OTFC and ketamine generally trended upward starting in 2012. In particular, the proportion of subjects receiving ketamine rose from 3.9% (n = 995/25,618) during the study period preceding its addition to the TCCC guidelines (2007 to 2012) to 19.8% thereafter (2013-2016, n = 515/2,604, p < 0.001). During the study period, rates of prehospital administration of IM morphine remained relatively stable while those for OTFC and ketamine both rose. These findings suggest that TCCC guidelines recommending the use of these agents had a material impact on prehospital analgesia patterns.


Dynamics of diabetes and obesity: Epidemiological perspective.
The purpose of this review article is to understand the current literature on obesity, diabetes and therapeutic avenues across the world. Diabetes is a chronic lifestyle condition that affects millions of people worldwide and it is a major health concern in our society. Diabetes and obesity are associated with various conditions, including non-modifiable and modifiable risk factors. Early detectable markers are not well established to detect pre-diabetes and as a result, it becomes diabetes. Several published epidemiological studies were assessed and the findings were summarized. Resources from published studies were used to identify criteria used for pre-diabetes, the role of diet in pre-diabetics and potential risks and characteristics associated with pre-diabetes. Preventive strategies are needed to combat diabetes. Individuals diagnosed with pre-diabetes need detailed education, need to fully understand the risk factors and have the ability to manage diabetes. Interventions exist that include chronic disease self-management programs, lifestyle interventions and pharmacological strategies. Obesity plays a large role in causing pre-diabetes and diabetes. Critical analysis of existing epidemiological research data suggests that additional research is needed to determine the efficacy of interventions. This article is part of a Special Issue entitled: Oxidative Stress and Mitochondrial Quality in Diabetes/Obesity and Critical Illness Spectrum of Diseases - edited by P. Hemachandra Reddy.