Novel application of proton pump inhibitor for the prevention of colitis-induced colorectal carcinogenesis beyond acid suppression.
Colitis-associated cancers arise in the setting of chronic inflammation wherein an "inflammation-dysplasia-carcinoma" sequence prevails. Based on our previous findings in which the proton pump inhibitor could impose significant levels of anti-inflammatory, antiangiogenic, and selective apoptosis induction beyond gastric acid suppression, we investigated whether omeprazole could prevent the development of colitis-associated cancer in a mouse model induced by repeated bouts of colitis. Omeprazole, 10 mg/kg, was given i.p. all through the experimental periods for colitis-associated carcinogenesis. Molecular changes regarding inflammation and carcinogenesis were compared between control groups and colitis-associated cancer groups treated with omeprazole in addition to chemopreventive outcome. Nine of 12 (75.0%) mice in the control group developed multiple colorectal tumors, whereas tumors were noted in only 3 of 12 (25.0%) mice treated with daily injections of omeprazole. The cancer-preventive results of omeprazole treatment was based on significant decreases in the levels of nitric oxide, thiobarbituric acid-reactive substance, and interleukin-6 accompanied with attenuated expressions of tumor necrosis factor-alpha, inducible nitric oxide synthase, and cyclooxygenase-2. The expressions of matrix metalloproteinase (MMP)-9, MMP-11, and MT1-MMMP were significantly decreased in mice treated with omeprazole in accordance with significant decreases in the number of beta-catenin-accumulated crypts. A significant induction of apoptosis was observed in tumor tissue treated with omeprazole. Omeprazole could block the trophic effect of gastrin in colon epithelial cells. The significant anti-inflammatory, antioxidative, and antimutagenic activities of omeprazole played a cancer-preventive role against colitis-induced carcinogenesis, and our novel in vivo evidence is suggestive of chemopreventive action independent of gastric acid suppression.


Bread Staling: Updating the View.
Staling of bread is cause of significant product waste in the world. We reviewed the literature of the last 10 y with the aim to give an up-to-date overview on processing/storage parameters, antistaling ingredients, sourdough technology, and measurement methods of the staling phenomenon. Many researchers have been focusing their interest on the selection of ingredients able to retard staling, mainly hydrocolloids, waxy wheat flours (WWF), and enzymes, but different efforts have been made to understand the molecular basis of bread staling with the help of various measurement methods. Results obtained confirm the central role of amylopectin retrogradation and water redistribution within the different polymers in determining bread staling, but highlighted also the importance of other flour constituents, such as proteins and nonstarch polysaccharides. Data obtained with thermal, spectroscopy, nuclear magnetic resonance, X-ray crystallography, and colorimetry analysis have pointed out the need to encourage the use of one or more of these techniques in order to better understand the mechanisms of staling. Results so far obtained have provided new insight on bread staling, but the phenomenon has not been fully elucidated so far.


Potential Role of Monocyte Chemoattractant Protein-1 in Monitoring Disease Progression and Response to Treatment in Overactive Bladder Patients.
To compare urinary levels of monocyte chemoattractant protein-1 (MCP-1), an inflammatory cytokine, in healthy controls and overactive bladder (OAB) patients, to correlate changes in urinary MCP-1 with OAB treatment response and symptom severity, and to study the diagnostic potential of MCP-1 for OAB, as well as the efficacy of MCP-1 as a potential biomarker for different phenotypes of OAB. We used enzyme-linked immunosorbent assay to measure normalized urinary MCP-1 levels in 56 individuals (43 OAB patients and 13 controls). We assessed the OAB patients at 3 visits with 2 validated symptom severity questionnaires (OAB-V8 and Patient Perception of Bladder Condition). The mean pretreatment urinary MCP-1 level at visit 1 (229.2-pg/mg creatinine) was significantly greater than the MCP-1 levels at visit 3 in both the treatment (107.0-pg/mg creatinine) (P<0.001) and control (52.35-pg/mg creatinine) groups (P<0.001). Average OAB symptom severity decreased significantly from visit 1 (baseline) to visits 2 (4 weeks) and 3 (12-14 weeks) and was significantly correlated with urinary MCP-1 levels. Urinary MCP-1 levels dropped significantly (P=0.002) posttreatment in patients whose symptom severity improved by >30%, whereas nonresponders displayed no significant MCP-1 decrease (P=0.164). The receiver operating characteristic analysis of the OAB visit 1 and control groups produced an area under the curve of 0.891. We found no significant differences in sex, race, or age between the OAB and control groups. MCP-1 levels differed significantly between the control and OAB groups and were closely correlated with symptom severity and treatment response. The good diagnostic accuracy of MCP-1 for OAB suggests the potential usage of MCP-1 for OAB diagnosis. The varying response of urinary MCP-1 levels to treatment may indicate at least 2 potential phenotypes of OAB. MCP-1, in combination with other biomarkers and symptom severity questionnaires, could potentially aid in developing a patient-centered OAB treatment approach.


Population genetics of the schistosome intermediate host Biomphalaria pfeifferi in the Zimbabwean highveld: implications for co-evolutionary theory.
Co-evolutionary theory proposes that polymorphisms in co-evolved traits may be maintained through differential selection in spatially heterogeneous environments. Spatial heterogeneity of the schistosome intermediate host, Biomphalaria pfeifferi, was investigated here, using RAPD markers. Overall, 256 individuals, collected at 32 sites on 13 rivers in the Chiweshe region of Zimbabwe, were analysed. Significant genetic differentiation was demonstrated, both between populations from the different rivers and between populations collected at different sites on each of several of the rivers investigated. However, the presence of spatial differentiation between populations from individual rivers varied with river type. It was not apparent in permanent, deep, fast-flowing rivers, where high levels of migration, through passive dispersal along the rivers, are likely. The snails collected from shallow, semi-permanent rivers not only showed relatively high levels of population subdivision but also high levels of within-site genetic diversity, consistent with the existence of 'co-evolutionary hot-spots' where schistosome infection may be prevalent. These results are discussed with reference to the population biology of B. pfeifferi and to host-parasite co-evolution.


Toward a mechanistic understanding and prediction of biotic homogenization.
The widespread replacement of native species with cosmopolitan, nonnative species is homogenizing the global fauna and flora. While the empirical study of biotic homogenization is substantial and growing, theoretical aspects have yet to be explored. Consequently, the breadth of possible ecological mechanisms that can shape current and future patterns and rates of homogenization remain largely unknown. Here, we develop a conceptual model that describes 14 potential scenarios by which species invasions and/or extinctions can lead to various trajectories of biotic homogenization (increased community similarity) or differentiation (decreased community similarity); we then use a simulation approach to explore the model's predictions. We found changes in community similarity to vary with the type and number of nonnative and native species, the historical degree of similarity among the communities, and, to a lesser degree, the richness of the recipient communities. Homogenization is greatest when similar species invade communities, causing either no extinction or differential extinction of native species. The model predictions are consistent with current empirical data for fish, bird, and plant communities and therefore may represent the dominant mechanisms of contemporary homogenization. We present a unifying model illustrating how the balance between invading and extinct species dictates the outcome of biotic homogenization. We conclude by discussing a number of critical but largely unrecognized issues that bear on the empirical study of biotic homogenization, including the importance of spatial scale, temporal scale, and data resolution. We argue that the study of biotic homogenization needs to be placed in a more mechanistic and predictive framework in order for studies to provide adequate guidance in conservation efforts to maintain regional distinctness of the global biota.


[Possible indications for temporalis muscle flaps in plastic-reconstructive surgery of the head and neck].
In reconstructive plastic surgery, the temporalis muscle has proven to be a reliable and versatile flap for a wide field of indications. The temporalis muscle is a flat, fanshaped muscle with a generous blood supply and innervation from the trigeminal nerve. Based on our own experiences in a total of 25 cases (12 cases involving muscle transposition for mouth reanimation, six cases involving stabilisation of a duraplasty including protecting the internal carotid artery in one case, four cases involving reconstruction of the orbital floor or the base of the skull, and three cases involving recontouring the lateral face) and a review of the literature we give an up-to-date overview of the different indications for the temporalis muscle flap. These include: a) treatment of facial nerve paralysis, b) recontouring of the lateral face, c) reconstruction of skull base, orbita, and oropharynx, d) stabilization of duraplasty, e) protection of internal carotid artery, f) in temporomandibular joint surgery, and g) for obliteration in ear surgery. Because of the wide range of indications, the temporalis muscle flap remains a versatile and important tool in plastic reconstructive surgery.


Visually guided and context-dependent spatial navigation in the translucent fish Danionella cerebrum.
Danionella cerebrum (DC) is a promising vertebrate animal model for systems neuroscience due to its small adult brain volume and inherent optical transparency, but the scope of their cognitive abilities remains an area of active research. In this work, we established a behavioral paradigm to study visual spatial navigation in DC and investigate their navigational capabilities and strategies. We initially observed that adult DC exhibit strong negative phototaxis in groups but less so as individuals. Using their dark preference as a motivator, we designed a spatial navigation task inspired by the Morris water maze. Through a series of environmental cue manipulations, we found that DC utilize visual cues to anticipate a reward location and found evidence for landmark-based navigational strategies wherein DC could use both proximal and distal visual cues. When subsets of proximal visual cues were occluded, DC were capable of using distant contextual visual information to solve the task, providing evidence for allocentric spatial navigation. Without proximal visual cues, DC tended to seek out a direct line of sight with at least one distal visual cue while maintaining a positional bias toward the reward location. In total, our behavioral results suggest that DC can be used to study the neural mechanisms underlying spatial navigation with cellular resolution imaging across an adult vertebrate brain.


Neuritogenic and neuroprotective activities of fruit residues.
Neuritogenic and neuroprotective activities of litchi (Litchi chinensis Sonn., Sapindaceae) and salacca (Salacca edulis Reinw., Arecaceae) pericarp, and sapodilla (Achras sapota L., Sapotaceae) and tamarind Srichompu cultivar (Tamarindus indica L., Caesalpiniaceae) seed coat extracts were evaluated on cultured cholinergic P19-derived neurons. All the extracts, at a very low concentration (1 ng/mL of litchi and salacca pericarp extracts, 10 ng/mL of sapodilla and 100 ng/mL of tamarind seed coat extracts), enhanced the survival of cultured neurons (% viability more than 100%) by XTT reduction assay. The extracts were further evaluated for their neuritogenicity by observing cell morphology by phase-contrast microscopy and neuroprotective activity in serum deprivation and pre- and co-administration of hydrogen peroxide models. The phase-contrast micrographs displayed that all of the extracts possessed neurogenic activity by promoting the neurite outgrowth of the cultured neurons. Moreover, these extracts can protect neurons from oxidative stress-caused cell death in a serum deprivation model, and prevent and protect neuron cells from the toxicity of hydrogen peroxide. In this study we assured that the neuritogenic and neuroprotective activities of these extracts derived from the phenolic components and flavonoids contained in the extracts by acting as signaling molecules to enhance neuron survival and promote neurite outgrowth. These results suggest that all of the extracts are potentially sources of neuritogenic and neuroprotective components which might be used either as pharmaceutical products or dietary supplements for neurodegenerative disorder patients, for example, those suffering from Alzheimer's disease.


Multiple [3H]-oxytocin binding sites in rat myometrial plasma membranes.
The affinity spectrum method has been used to analyse binding isotherms for [3H]-oxytocin to rat myometrial plasma membranes. Three populations of binding sites with dissociation constants (Kd) of 0.6-1.5 x 10(-9), 0.4-1.0 x 10(-7) and 7 x 10(-6) mol/l were identified and their existence verified by cluster analysis based on similarities between Kd, binding capacity and Hill coefficient. When experimental values were compared to theoretical curves constructed using the estimated binding parameters, good fits were obtained. Binding parameters obtained by this method were not influenced by the presence of GTP gamma S (guanosine-5'-O-(3-thiotriphosphate) in the incubation medium. The binding parameters agree reasonably well with those found in uterine cells, they support the existence of a medium affinity site and may allow for an explanation of some of the discrepancies between binding and response in this system.


Acquired cerebral hemiatrophy: Dyke-Davidoff-Masson Syndrome - a case report.
A rare syndrome, Dyke-Davidoff-Masson Syndrome (DDMS), with a diagnostic conundrum, and the way it was solved is presented. A 13-year-old boy presented with recurrent seizures for the past 10 years. He had been treated with anticonvulsant medication which was satisfactory at first but later the seizures recurred. Recently, the frequency of the seizures increased with preictal dizziness and postictal drowsiness. Physical examination revealed mild left hemiparesis and left deviated gait irregularity. He was mentally alert but had not achieved all the developmental milestones as compared to normal child of his age. CT and MRI scan of the head showed hemiatrophic cerebral parenchyma with prominent sulci and encephalomalacia. 24-hour intensive video EEG monitoring revealed suppression of alpha rhythm and local slow wave activity on the side of the atrophic hemisphere. PET-CT showed highly functional left cerebral hemisphere and less functional right cerebral hemisphere. The patient underwent functional hemispherectomy under neurophysiological monitoring and the nonfunctional brain tissues were resected while selectively preserving the functional areas detected by fMRI and PET-CT scan. During follow up, the patient was seizure free as well as without difficulties in performing his daily activities and communications. Functional hemispherectomy for DDMS patient has a good prognosis.


Nutritional Assessment of Adult Patients Undergoing Maintenance Hemodialysis in the Gaza Strip.
Malnutrition is a common condition in patients undergoing hemodialysis (HD), and it is associated with increased morbidity and mortality. The main objective of the study was to evaluate the nutritional status of patients on maintenance HD. After applying eligibility criteria, 141 HD patients attending major governmental dialysis centers were randomly recruited in this cross-sectional study and assessed for nutritional status using the Patient-Generated Subjective Global Assessment (PG-SGA) tool. The PG-SGA categorizes patients as well-nourished, moderately malnourished, and severely malnourished. Different anthropometric measurements, laboratory investigations, blood pressure measurements, and 24-h dietary recall were collected from each patient. According to PG- SGA results, 78% of patients were moderately malnourished and 22% of patients were severely malnourished. The mean body mass index was 27.8 kg/m2, and 5.7% of patients were underweight. There were significant differences in the mid-upper arm muscle circumference (P = 0.020) between the PG-SGA groups. The total energy and protein intake were significantly (P <0.001) less than the recommended dietary intake by 1268.9 kcal and 41.4 g, respectively. The albumin level in 37.6% of patients was less than the normal level, and the results indicated that there were significant differences in serum iron (P = 0.022) between the moderately and severely malnourished patients. The results of this study indicated that all HD patients were suffering from different degrees of malnutrition and, unfortunately, most of their energy and nutrient intake was far less than the requirements, which might be the reason why they face nutritional and health risks.


Anatomic site-specific positive margins in organ-confined prostate cancer and its impact on outcome after radical prostatectomy.
The impact of a positive surgical margin in otherwise confined prostate cancer after radical prostatectomy remains unclear. We analyzed the outcome of a large number of patients with organ-confined prostate cancer according to the presence and anatomic site of margin positivity. We evaluated 2712 prostatectomy patients with Stage pT2N0 cancer (ie, no evidence of extra-prostatic disease, seminal vesicle or regional node involvement) and no prior therapy who were treated by radical prostatectomy between 1987 and 1995 at Mayo Clinic. A total of 697 patients (26%) had positive margins. To assess the effect of margin status in the absence of treatment, 378 patients with postoperative adjuvant therapy were not considered for the study group: the final group consisted of 2334 patients. Overall, 253 (58%) tumors were positive at the apex and/or urethra, 85 (19%) at the prostate base, 11 (2.5%) at the anterior prostate, and 174 (40%) at the posterior prostate; 89 (20%) had at least two margins involved and 21 (8.3%) had more than two involved. The apex/urethra was the only positive anatomic site in 183 (42%). Five-year survival free of clinical recurrence or prostate-specific antigen (PSA) biochemical failure (postoperative serum PSA of 0.2 ng/mL or more) for patients with a single positive margin was 79% for apex or urethra, 78% for anterior/posterior, and 56% for prostate base. Five-year survival free of clinical recurrence or PSA (biochemical) failure was slightly higher for those with one versus two margin-positive regions (77% versus 68%, respectively). Multivariate analysis revealed that positive surgical margins were a significant predictor of clinical recurrence and PSA (biochemical) failure (relative risk [95% confidence interval]: 1.65 [1.24, 2.18]) after controlling for Gleason grade, preoperative PSA, and deoxyribonucleic acid (DNA) ploidy. The effect of margin positivity on recurrence at a specific anatomic site (versus negative margins or positive at a different anatomic site) revealed the prostate base to be the only significant anatomic site when adjusted for grade, PSA, and ploidy. Five-year survival free of the combined clinical or PSA failure end point for those with versus those without positive margins at the prostate base was 56% versus 85%, respectively (P < 0.0001). Positive surgical margins are a significant predictor of recurrence in Stage pT2N0 cancer, which is independent of grade, PSA, and DNA ploidy. The impact of positive margin status on recurrence-free survival appears to be anatomic and site-specific, with prostate base positivity significantly associated with poor outcome. The benefit of adjuvant therapy based on anatomic site-specific margin positivity remains to be tested in order to optimize recurrence-free survival.


Alterations to melanocortinergic, GABAergic and cannabinoid neurotransmission associated with olanzapine-induced weight gain.
Second generation antipsychotics (SGAs) are used to treat schizophrenia but can cause serious metabolic side-effects, such as obesity and diabetes. This study examined the effects of low to high doses of olanzapine on appetite/metabolic regulatory signals in the hypothalamus and brainstem to elucidate the mechanisms underlying olanzapine-induced obesity. Levels of pro-opiomelanocortin (POMC), neuropeptide Y (NPY) and glutamic acid decarboxylase (GAD(65), enzyme for GABA synthesis) mRNA expression, and cannabinoid CB1 receptor (CB1R) binding density (using [(3)H]SR-141716A) were examined in the arcuate nucleus (Arc) and dorsal vagal complex (DVC) of female Sprague Dawley rats following 0.25, 0.5, 1.0 or 2.0 mg/kg olanzapine or vehicle (3×/day, 14-days). Consistent with its weight gain liability, olanzapine significantly decreased anorexigenic POMC and increased orexigenic NPY mRNA expression in a dose-sensitive manner in the Arc. GAD(65) mRNA expression increased and CB1R binding density decreased in the Arc and DVC. Alterations to neurotransmission signals in the brain significantly correlated with body weight and adiposity. The minimum dosage threshold required to induce weight gain in the rat was 0.5 mg/kg olanzapine. Olanzapine-induced weight gain is associated with reduced appetite-inhibiting POMC and increased NPY. This study also supports a role for the CB1R and GABA in the mechanisms underlying weight gain side-effects, possibly by altering POMC transmission. Metabolic dysfunction can be modelled in the female rat using low, clinically-comparable olanzapine doses when administered in-line with the half-life of the drug.


The tumor suppressor UCHL1 forms a complex with p53/MDM2/ARF to promote p53 signaling and is frequently silenced in nasopharyngeal carcinoma.
Nasopharyngeal carcinoma is prevalent in southern China and Southeast Asia, with distinct geographic and ethnic distribution. One candidate susceptibility locus has been identified at 4p11-14, with the associated candidate gene(s) not identified yet. This study investigated the role of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) in nasopharyngeal carcinoma pathogenesis. UCHL1 expression and methylation were examined in nasopharyngeal carcinoma. Furthermore, the mechanism of its tumor-suppressive function was elucidated in nasopharyngeal carcinoma cells. Through genomewide expression profiling, we identified UCHL1, a 4p14 gene normally expressed in normal upper respiratory tract tissues, being silenced in all nasopharyngeal carcinoma cell lines. Its silencing is mediated by CpG methylation because UCHL1 promoter methylation was detected in all silenced cell lines, and pharmacologic demethylation reactivated UCHL1 expression along with concomitant promoter demethylation. UCHL1 methylation was also frequently detected in primary tumors but only weakly detected in few normal nasopharyngeal tissues, indicating that the methylation-mediated silencing of UCHL1 is important in nasopharyngeal carcinoma pathogenesis. Ectopic UCHL1 expression dramatically inhibited the growth of nasopharyngeal carcinoma cells through promoting tumor cell apoptosis. We further found that UCHL1 formed a complex with p53/p14(ARF)/Mdm2 p53 binding protein homolog (mouse), MDM2 and activated the p53 signaling pathway. UCHL1 expression extended p53 and p14(ARF) protein half-life and shortened MDM2 protein half-life. These results indicate that UCHL1 could deubiquitinate p53 and p14(ARF) and ubiquitinate MDM2 for p53 stabilization to promote p53 signaling, thus involved in nasopharyngeal carcinoma pathogenesis, whereas it is frequently silenced in this tumor.


Rational engineering and insight for a L-glutaminase activity reduced type II L-asparaginase from Bacillus licheniformis and its antileukemic activity in vitro.
Type II L-asparaginase (ASNase) has been approved by the FDA for treating acute lymphoid leukemia (ALL), but its therapeutic effect is limited by low catalytic efficiency and L-glutaminase (L-Gln) activity. This study utilized free energy based molecular dynamics calculations to identify residues associated with substrate binding in Bacillus licheniformis L-asparaginase II (BLASNase) with high catalytical activity. After saturation and combination mutagenesis, the mutant LGT (74 L/75G/111 T) with intensively reduced l-glutamine catalytic activity was generated. The l-glutamine/L-asparagine activity (L-Gln/L-Asn) of LGT was only 6.6 % of parent BLASNase, whereas the L-asparagine (L-Asn) activity was preserved >90 %. Furthermore, structural comparison and molecular dynamics calculations indicated that the mutant LGT had reduced binding ability and affinity towards l-glutamine. To evaluate its effect on acute leukemic cells, LGT was supplied in treating MOLT-4 cells. The experimental results demonstrated that LGT was more cytotoxic and promoted apoptosis compared with commercial Escherichia coli ASNase. Overall, our findings firstly provide insights into reducing l-glutamine activity without impacting L-asparagine activity for BLASNase to possess remarkable potential for anti-leukemia therapy.


The EMBL data library.
The EMBL Data Library was the first internationally supported central resource for nucleic acid sequence data. Working in close collaboration with its American counterpart, GenBank (1), the library prepares and makes available to the scientific community a comprehensive collection of the published nucleic acid sequences. This paper describes briefly the contents of the database, how it is available, and possible future enhancements of Data Library services.


Intention to apply or accept an alternative job among participants of extended employment programs.
The research studied 249 people employed in extended employment programs in northern Israel with respect to their intention to apply for an alternative job (an active step) or to accept a new job offer (a passive step). Findings indicated that young, single people who were living with their parents and perceived their level of disability as mild indicated more intention to apply for an alternative job or to accept a new job offer. Furthermore, people with low monthly wages, less satisfaction with their income and with the extended employment program in general, and a lack of participation in non-employment activities expressed a greater inclination to apply for an alternative job or to accept a new job offer. The only difference between people's intentions to apply for an alternative job (an active step) or to accept a job offer (a passive step) was in regard to their perception of their disability. The intention to apply for an alternative job was associated with mild disability, whereas the acceptance of a new job offer was related to mild and moderate disability.


Nipple-Sparing Mastectomy in Breast Cancer: Impact on Surgical Resection, Oncologic Safety, and Psychological Well-Being.
Nipple-sparing mastectomy (NSM) is a surgical option to improve patient satisfaction with aesthetic outcome. It can be utilized to decrease body image disturbance by preserving the woman's skin and areolar complex. Data for cancer treatment and risk reduction in NSM shows the procedure is oncologically safe. Nipple-sparing mastectomy preserves the nipple to improve cosmetic appearance. Patient satisfaction is higher for NSM compared with traditional mastectomy. PubMed and Cochrane databases were searched from January 1, 2013, to December 22, 2019. The following search terms and keywords were used: nipple-sparing mastectomy, microvascular breast reconstruction, breast cancer, and nipple necrosis. Studies published in scientific journals that reported objective results (specific outcomes of skin flap and nipple-areola complex necrosis) were included. Nipple-sparing mastectomy should be discussed as a surgical option for women who meet the selection criteria to assist with psychological benefits related to body image. Research comparing levels of distress and body image disturbances in women undergoing NSM with traditional mastectomy would be helpful in addressing the psychological care of these women. Ongoing data collection needs to continue to validate that NSM is safe from a surgical and an oncologic standpoint.


Myelopathy due to degenerative and structural spine diseases.
This article reviews the current evaluation and treatment of patients with myelopathy due to cervical spondylotic disease and other structural disorders of the spine. In patients with cervical spondylotic myelopathy, symptom duration, severity at baseline, and possibly age have been identified as key prognostic markers of clinical course and postsurgical outcome. Other potential markers include specific MRI and EMG findings. The diagnosis and monitoring of syringomyelia is enhanced by the addition of phase contrast MRI, which evaluates CSF flow dynamics. Flexion MRI is helpful in establishing the diagnosis of Hirayama disease, which is now attributed to a tightened dural sac that is displaced anteriorly on neck flexion, compressing the cord. Advances in neuroimaging along with new insights into the pathophysiology of structural spine diseases can help guide clinical decision making and optimize patient outcomes.


Efficacy of elective lymph node dissection in 2,347 patients with clinical stage I malignant melanoma.
The results of a largely prospective but non-randomized study of 2,347 patients with clinical Stage I malignant melanoma have demonstrated that there are certain subgroups of patients who benefit substantially from ELND. Men with lesions of intermediate thickness (1.6 to 3.0 millimeters) benefited most from ELND, both in terms of disease-free and total survival rates. Ten year survival rates in patients who underwent ELND were more than 40 per cent higher than the rates in patients who underwent WE. Although total survival rates were not improved in patients with the thickest lesions (those in excess of 3.0 millimeters) disease-free rates in these patients were considerably higher after ELND. Women with lesions of the extremities thicker than 1.5 millimeters had significantly improved disease-free and total survival rates after ELND (ten year survival rates of up to 37 per cent higher after ELND). No women with lesions of the trunk appeared to benefit from this surgical procedure.


Efficacy of Distal Pancreatectomy Combined With Modified DuVal Procedure in Patients With a High Risk of Postoperative Pancreatic Fistula.
The incidence of postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP) remains high. The present study aimed to clarify the efficacy of our modified DuVal (mDuVal) pancreatojejunostomy following DP in patients with a high risk of POPF. The medical records of 346 consecutive patients who underwent DP between 2006 and 2016 were retrospectively reviewed. Perioperative features were compared between 24 patients undergoing mDuVal (mDuVal group) and 322 patients undergoing standard DP (standard DP group). Preoperative American Society of Anesthesiologists physical status 1 was more frequent in the standard group than in the mDuVal group (P = .02). The start of a solid diet after operation was significantly earlier in the mDuVal group than in the standard DP group (P = .01), while there were no significant differences between the groups for clinically relevant POPF, amylase concentration in the drainage fluid on postoperative day 1 and days 3-5, time to drain removal, additional intervention for POPF, overall complications, or postoperative hospital stay. The mDuVal procedure could be an option for patients with a high risk of POPF to improve the outcomes after DP. Further investigation involving large study populations is necessary to clarify the efficacy of this procedure.


[Stimulation of nonspecific body resistance in transplantation].
The experiments on mice showed in principle a possibility of using prodigiozan, a stimulant of the host immunobiological reactivity together with immunodepressants in transplantation. Imuran in doses of 25 or 60 mg/kg and prednisolone in doses of 30 or 50 mg/kg were used on alternate days at a rate of 5 injections of every drug per course. Prodigiozan was administered intramuscularly in a dose of 0.5 mg/kg on the 4th and 8th-9th days of the immunodepressant administration. Addition of prodigiozan to the scheme of the combined use of the immunodepressants provided an increase in the survival rate of mice with staphylococcal and coli infections and prolongation of the skin allotransplant rejection time. No effect of prodigiozan on immune depression due to imuran was observed. The results suggest that screening of drugs for the use in transplanthology for prevention of infectious complications in the presence of immunostimulants is advisable among stimulants of the host nonspecific resistance.


Community acquired pneumonia incidence before and after proton pump inhibitor prescription: population based study.
Objective To examine the risk of community acquired pneumonia before and after prescription of proton pump inhibitor (PPI) and assess whether unmeasured confounding explains this association.Design Cohort study and self controlled case series.Setting Clinical Practice Research Datalink (1990 to 2013) in UK.Participants Adult patients with a new prescription for a PPI individually matched with controls.Main outcome measures Association of community acquired pneumonia with PPI prescription estimated by three methods: a multivariable Cox model comparing risk in PPI exposed patients with controls, corrected for potential confounders; a self controlled case series; and a prior event rate ratio (PERR) analysis over the 12 month periods before and after the first PPI prescription.Results 160 000 new PPI users were examined. The adjusted Cox regression showed a risk of community acquired pneumonia 1.67 (95% confidence interval 1.55 to 1.79) times higher for patients exposed to PPI than for controls. In the self controlled case series, among 48 451 PPI exposed patients with a record of community acquired pneumonia, the incidence rate ratio was 1.19 (95% confidence interval 1.14 to 1.25) in the 30 days after PPI prescription but was higher in the 30 days before a PPI prescription (1.92, 1.84 to 2.00). The Cox regressions for prior event rate ratio similarly showed a greater increase in community acquired pneumonia in the year before than the year after PPI prescription, such that the analysis showed a reduced relative risk of pneumonia associated with PPI use (prior event rate ratio 0.91, 95% confidence interval 0.83 to 0.99).Conclusion The association between the use of PPIs and risk of community acquired pneumonia is likely to be due entirely to confounding factors.


Interpolar microtubules are dispensable in fission yeast meiosis II.
The mitotic spindle consists of two types of microtubules. Dynamic kinetochore microtubules capture kinetochores, whereas stable interpolar microtubules serve as the structural backbone that connects the two spindle poles. Both have been believed to be indispensable for cell division in eukaryotes. Here we demonstrate that interpolar microtubules are dispensable for the second division of meiosis in fission yeast. Even when interpolar microtubules are disrupted by a microtubule-depolymerizing drug, spindle poles separate and chromosomes segregate poleward in second division of meiosis in most zygotes, producing viable spores. The forespore membrane, which encapsulates the nucleus in second division of meiosis and is guided by septins and the leading-edge proteins, is responsible for carrying out meiotic events in the absence of interpolar microtubules. Furthermore, during physiological second division of meiosis without microtubule perturbation, the forespore membrane assembly contributes structurally to spindle pole separation and nuclear division, generating sufficient force for spindle pole separation and subsequent events independently of interpolar microtubules.


Responsible gambling among older adults: a qualitative exploration.
Responsible gambling (RG) is defined as gambling for pleasure and entertainment but with an awareness of the likelihood of losing, an understanding of the associated risks and the ability to exercise control over one's gambling activity. The current study describes a qualitative approach to explore RG among older adults (aged 60 years and above) in Singapore and reports on the cognitive and behavioural strategies employed by them to regulate their gambling. Inclusion criteria included Singapore residents aged 60 years and above, who could speak in English, Chinese, Malay or Tamil and were current or past regular gamblers. Participants were recruited using a combination of network and purposive sampling. Socio-demographic information on age, age of onset of gambling, gender, ethnicity, marital status, education and employment was collected. The South Oaks Gambling Screen (SOGS) was used to collect information on gambling activities and problems associated with gambling behaviour. Qualitative interviews were conducted with 25 older adults (60 years and above) who currently gambled. The data was analyzed using thematic network analysis. This global theme of RG comprised two organising themes: self -developed strategies to limit gambling related harm and family interventions to reduce gambling harm. The basic themes included delayed gratification, perception of futility of gambling, setting limits, maintaining balance, help-seeking and awareness of disordered gambling in self or in others. Family interventions included pleading and threatening, compelling help-seeking as well as family exclusion order. The study highlights the significant role that families play in Asian societies in imposing RG. Education of family members both in terms of the importance of RG, and communication of the ways in which older adults can incorporate RG behaviours including the use of exclusion in specific scenarios is important.


Behaviour and dynamics of di-ammonium phosphate in bauxite processing residue sand in Western Australia--I. NH3 volatilisation and residual nitrogen availability.
Australia is the largest producer of bauxite in the world, with an annual output of approximately 62 million metric dry tons in 2007. For every tonne of alumina, about 2 tonnes of highly alkaline and highly saline bauxite-processing residue are produced. In Western Australia, Alcoa World Alumina, Australia (Alcoa) produces approximately 15 MT of residue annually from its refineries (Kwinana, Pinjarra and Wagerup). The bauxite-processing residue sand (BRS) fraction represents the primary material for rehabilitating Alcoa's residue disposal areas (RDAs). However, the inherently hostile characteristics (high alkalinity, high salinity and poor nutrient availability) of BRS pose severe limitations for establishing sustainable plant cover systems. Alcoa currently applies 2.7 t ha(-1) of di-ammonium phosphate ((NH(4))(2)HPO(4); DAP)-based fertiliser as a part of rehabilitation of the outer residue sand embankments of its RDAs. Limited information on the behaviour of the dominant components of this inorganic fertiliser in highly alkaline BRS is currently available, despite the known effects of pH on ammonium (NH(4)) and phosphorus (P) behaviour. The aim of this study was to quantify the effects of pH on NH(3) volatilisation and residual nitrogen (N) in BRS following DAP applications. The sponge-trapping and KCl-extraction method was used for determining NH(3) volatilisation from surface-applied DAP in samples of BRS collected from each of Alcoa's three Western Australia Refineries (Kwinana, Pinjarra, Wagerup) under various pH conditions (pH 4, 7, 9 and 11). Following cessation of volatilisation, the residual N was extracted from BRS using 2 M KCl and concentrations of NH (4) (+) -N and NO (3) (-) -N were determined by flow injection analysis. The quantities of NH(3) volatilised increased dramatically as the pH increased from 4 to 11. Much of the N lost as NH(3) (up to 95.2%) occurred within a short period (24 h to 7 days), particularly for the pH 9 and 11 treatments. Concentrations of residual NH (4) (+) -N recovered in DAP-treated BRS at the end of the experiment decreased with increasing pH. This finding was consistent with increasing loss of N via volatilisation as pH increased. The concentration of NO (3) (-) -N was very low due to no nitrification in BRS. The pH was a key driver for NH(3) volatilisation from DAP-treated BRS and primarily controlled N dynamics in BRS. Results indicate that NH(4) not adsorbed by BRS was highly susceptible to volatilisation. The likely lack of nitrifying bacteria did not allow conversion of ammonium to nitrate, thereby further exacerbating the potential for loss via volatilisation It was demonstrated that the pH is the key factor controlling the loss of inorganic N from BRS. Although volatilisation was considerably lower at pH 4, achieving this pH reduction in the field is not possible at present. Findings from this study highlight the need to better understand which forms of N fertiliser are most suitable for use in highly alkaline BRS. Although pH reduction is the most likely means of stopping NH(3) volatilisation in BRS, it is economically and operationally unfeasible to add sufficient acidity for adequately lowering pH in the BRS for revegetation. More attention on forms of fertilisers more suitable to highly alkaline, microbially inert soil conditions appears to be warranted.


Fracture strength of secondary crown with different taper and thickness in zirconia double crown attachments.
The objective of this study was to clarify the influences of zirconia materials, one-half taper angle, and thickness of the secondary crown on the fracture strength of the secondary crown. For the primary and secondary crowns, Y-TZP and Ce-TZP/Al2O3 were used, respectively. Samples were prepared at one-half taper angles of 2° and 4°, and a secondary crown thickness of 0.5 and 1.0 mm (n=8). Regarding the fracture strength, the secondary crown was restored on the primary crown, all specimens were loaded until fracture using a universal testing machine. The load value added at the time of secondary crown fracture was regarded as fracture strength. Based on the analysis of variance, the fracture strength of Ce-TZP/Al2O3 was significantly higher than that of Y-TZP with regard to the material and that at 1.0-mm thickness was significantly higher than that at 0.5-mm thickness, but the taper angle had no influence.