Highly Homogeneous Current Transport in Ultra-Thin Aluminum Nitride (AlN) Epitaxial Films on Gallium Nitride (GaN) Deposited by Plasma Enhanced Atomic Layer Deposition.
This paper reports an investigation of the structural, chemical and electrical properties of ultra-thin (5 nm) aluminum nitride (AlN) films grown by plasma enhanced atomic layer deposition (PE-ALD) on gallium nitride (GaN). A uniform and conformal coverage of the GaN substrate was demonstrated by morphological analyses of as-deposited AlN films. Transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS) analyses showed a sharp epitaxial interface with GaN for the first AlN atomic layers, while a deviation from the perfect wurtzite stacking and oxygen contamination were detected in the upper part of the film. This epitaxial interface resulted in the formation of a two-dimensional electron gas (2DEG) with a sheet charge density ns ≈ 1.45 × 1012 cm-2, revealed by Hg-probe capacitance-voltage (C-V) analyses. Nanoscale resolution current mapping and current-voltage (I-V) measurements by conductive atomic force microscopy (C-AFM) showed a highly homogeneous current transport through the 5 nm AlN barrier, while a uniform flat-band voltage (VFB ≈ 0.3 V) for the AlN/GaN heterostructure was demonstrated by scanning capacitance microscopy (SCM). Electron transport through the AlN film was shown to follow the Fowler-Nordheim (FN) tunneling mechanism with an average barrier height of <ΦB> = 2.08 eV, in good agreement with the expected AlN/GaN conduction band offset.


Mechanism of glyceraldehyde-3-phosphate transfer from aldolase to glyceraldehyde-3-phosphate dehydrogenase.
The catalytic interaction of glyceraldehyde-3-phosphate dehydrogenase with glyceraldehyde 3-phosphate has been examined by transient-state kinetic methods. The results confirm previous reports that the apparent Km for oxidative phosphorylation of glyceraldehyde 3-phosphate decreases at least 50-fold when the substrate is generated in a coupled reaction system through the action of aldolase on fructose 1,6-bisphosphate, but lend no support to the proposal that glyceraldehyde 3-phosphate is directly transferred between the two enzymes without prior release to the reaction medium. A theoretical analysis is presented which shows that the kinetic behaviour of the coupled two-enzyme system is compatible in all respects tested with a free-diffusion mechanism for the transfer of glyceraldehyde 3-phosphate from the producing enzyme to the consuming one.


Role of calcium antagonists in cerebral arterial spasm.
Spasm of the large cerebral arteries at the base of the brain causes delayed ischemic neurologic deficits in approximately 30% of patients after a subarachnoid hemorrhage from an intracranial aneurysm. In vitro chamber studies have shown that both dog and human large cerebral artery segments contract to a variety of vasoactive agents, and the dog and human segments are remarkedly similar in their responses. The source of calcium necessary to initiate contraction was found to be extracellular for large cerebral arteries. In contrast, systemic arteries such as the femoral artery use a bound intracellular pool of calcium for contraction. The calcium antagonists nifedipine and nimodipine were found to selectively inhibit the contractions of large cerebral arteries but not the femoral artery. In vivo experiments demonstrated that both nifedipine and nimodipine, given sublingually, would prevent and reverse cerebral arterial spasm in the dog after a subarachnoid hemorrhage. Nimodipine was found to be more potent, both in the chamber and in the live dog experiments. Nimodipine significantly decreased the occurrence of severe neurologic deficits from spasm alone in a multi-institutional, prospective, double-blind, randomized, placebo-controlled trial.


Cervicofacial necrotizing fasciitis: report of three cases and literature review.
Three cases of cervicofacial necrotizing fasciitis have been reported, two of dental etiology, and one the result of blunt and abrasive facial trauma. All cases responded well to aggressive surgical intervention in combination with broad spectrum antibiotic coverage and supportive medical therapy. The presence of increased vascularity in the head and neck region probably minimizes the amount of overlying soft tissue that must be excised during surgical management (in comparison to extremity and trunk necrotizing fasciitis cases). The key to successful management of such infections is early diagnosis of the disease process with prompt surgical and medical intervention.


Trends in "green" and novel methods of pectin modification - A review.
Modification of hydrocolloids to alter their functional properties using chemical methods is well documented in the literature. There has been a recent trend of adopting eco-friendly and "green" methods for modification. Pectin, being a very important hydrocolloid finds its use in various food applications due to its gelling, emulsifying, and stabilizing properties. The adoption of various "green" methods can alter the properties of pectin and make it more suitable for incorporation in food products. The novel approaches such as microwave and pulsed electric field can also be utilized for solvent-free modification, making it desirable from the perspective of sustainability, as it reduces the consumption of organic chemicals. Pectic oligosaccharides (POSs) produced via novel approaches are being explored for their biological properties and incorporation in various functional foods. The review can help to set the perspective of potential scale-up and adoption by the food industry for modification of pectin.


pH-Dependent peptide bond formation by the selective coupling of α-amino acids in water.
A novel mechanism enabling selective peptide elongation by coupling α-amino acids over other potentially competing prebiotic amines under acidic aqueous condition is suggested. It proceeds via the generation of a carboxylic acid anhydride intermediate with subsequent intramolecular formation of the amide bond.


In vitro hemocompatibility of PVA-alginate ester as a candidate for hemodialysis membrane.
Alginate based biopolymer with improved physical and chemical properties after esterification using polyvinyl alcohol (PVA) has been studied for possible application as a hemodialysis membrane. The alginic acid to vinyl alcohol molar ratio was predetermined at 0, 0.1, 0.5 and 1. Mechanical strength, hydrophilicity and Ca(2+) adsorption of the membrane before and after modification were evaluated. The obtained PVA-alginate (PVA-Alg) ester membrane was also confirmed using FTIR and SEM. It shows that the PVA-Alg membrane tensile strength is higher than that of native alginate. The water contact angle of the membrane was found to be around 33-50°. The Ca(2+) adsorption capacity tends to decrease with the increase in molar ratio. Furthermore, the modified PVA-Alg ester membrane achieves better protein adsorption and platelet adhesion than the unmodified one. It also exhibits a dialysis performance of 47.1-50.0% for clearance of urea and 42.2-44.6% for clearance of creatinine, respectively. It is expected that this PVA-Alg ester may challenge cellulose acetate for potential application as hemodialysis membranes.


A comparison of Saint Louis encephalitis and Sindbis virus RNA.
RNA isolated from purified St. Louis encephalitis and Sindbis virus particles was compared by cellulose CF-11 chromatography, and RNase T1 and pancreatic RNase A digestion. SLE RNA eluted from the cellulose CF-11 column as a molecule with very little secondary structure, while Sindbis appears to have some internal bonding. Ribonuclease digestion indicates that SLE RNA contains 2.4 per cent polyadenylic acid.


Richard Lower: the origins of blood transfusion.
Millions of blood transfusions are performed yearly worldwide. With respect to its historical origins, this practice began in the 17(th) century with an English physician. In 1666, Richard Lower reported the first successful transfusion between animals. The first transfusion in a human patient was performed the following year by Jean Baptiste Denis, a French physician. That same year, Lower transfused blood from a lamb into the bloodstream of a clergyman named Arthur Coga. However, the practice was subsequently abandoned for hundreds of years. Safe transfusion awaited the recognition of blood types and cross-matching, and did not occur until early in the 20(th) century. A number of other advances in transfusion therapy have followed, and more are in development.


Cleavage activity of the sapovirus 3C-like protease in Escherichia coli.
We recently determined the ORF1 cleavage map of Mc10, a human sapovirus (SaV) strain, as follows: NH2-p11-p28-p35(NTPase)-p32-p14(VPg)-p70(Pro-Pol)-p60(VP1)-COOH. This cleavage was dependent on the viral encoded 3C-like protease. To identify the cleavage site of SaV ORF1, putative p70 (Pro-Pol) and p14-p70 (VPg-Pro-Pol) were expressed as N-terminal GST and C-terminal 6 x His-tag fusion proteins in Escherichia coli, and the expressed products were analyzed by SDS-PAGE and Western blotting. Our results indicated that the efficient proteolytic cleavage occurred between p14 (VPg) and p70 (Pro-Pol), and N-terminal amino acid sequencing revealed that the cleavage site was between E(1055) and A(1056). In contrast, the p70 (Pro-Pol) was not further cleaved. We also found that SaV protease cleaved the Q/G site within the rhinovirus 3C protease recognition site. Site-directed mutagenesis in a conserved GDCG motif of the protease completely abolished these proteolytic activities. This is the first report to identify the cleavage site of the SaV ORF1 polyprotein.


Serum lactate dehydrogenase level as a prognostic factor in Hodgkin's disease.
The efficacy of currently available treatments for Hodgkin's disease (HD) has led to a substantial modification in the prognosis of this disease; nevertheless there is still a group of patients that cannot be cured with conventional treatments and who will be candidates for alternative therapy. In the present work we analysed the prognostic influence of the most relevant clinico-biological characteristics of HD in a consecutive series of 137 patients diagnosed and treated in a single institution. Univariate analyses identified six variables with significant prognostic influence, both on achieving complete remission (CR) and overall survival (OS); LDH > 320 U ml-1, age > 45 years, stages IIB, III and IV, extranodal involvement, alkaline phosphatase > 190 UI dl and ESR > 40 mm h. In addition, Hb < 12.5 gr dl-1 and abdominal disease were statistically relevant for CR while a poor performance score (ECOG > or = 2) affected a lower survival. In the multivariate analysis only LDH, age and the clinical stage retained a significant prognostic influence for achieving CR, while the two first factors above, together with performance status were the variables with independent prognostic value with respect to OS. Moreover, only LDH > 320 U ml-1 had prognostic influence in the probability of relapse and disease free survival (DFS), both in the univariate and multivariate analyses. According to the three independent factors obtained in the multivariate analysis for CR (LDH, age and stage) a predictive model was established that allows the stratification of patients into two prognostic groups: one with poor prognosis that includes patients with the three adverse prognostic factors, or two if one of them was elevated LDH, and the other with good prognosis that includes the remaining patients. This model was also able to separate two independent groups of patients with respect to OS and to DFS. In conclusion, the present study shows that LDH is one of the most important prognostic factors in HD.


Severe and rapid erosion of dental enamel from swimming: a clinical report.
The diagnosis and treatment of a patient with excessive and rapid erosion of enamel is presented. Although the Center for Disease Control and the dental literature have reported on dental enamel erosion resulting from swimming pool chlorination, the awareness of such etiology among dental professionals may be limited. Common findings in these reports include cold sensitivity, a distinctive appearance resembling laminate veneer preparations of the facial surfaces of anterior teeth, occurrence of diastemas, and at times, a rough or gritty texture of the remaining tooth structure. Clinical presentations of erosive lesions can be diagnosed and the best course of treatment determined.


Curcumin induces mitophagy by promoting mitochondrial succinate dehydrogenase activity and sensitizes human papillary thyroid carcinoma BCPAP cells to radioiodine treatment.
Thyroid cancer is one of the most common endocrine malignancies. Differentiated thyroid cancer (DTC) treatment is based on the ability of thyroid follicular cells to accumulate radioactive iodide (RAI). DTC generally has a good prognosis. However, tumor dedifferentiation or defect in certain cell death mechanism occurs in a subset of DTC patients, leading to RAI resistance. Therefore, developing novel therapeutic approaches that enhance RAI sensitivity are still warranted. We found that curcumin, an active ingredient in turmeric with anti-cancer properties, rapidly accumulated in the mitochondria of thyroid cancer cells but not normal epithelial cells. Curcumin treatment triggered mitochondrial membrane depolarization, engulfment of mitochondria within autophagosomes and a robust decrease in mitochondrial mass and proteins, indicating that curcumin selectively induced mitophagy in thyroid cancer cells. In addition, curcumin-induced mitophagic cell death and its synergistic cytotoxic effect with radioiodine could be attenuated by autophagy inhibitor, 3-methyladenine (3-MA). Interestingly, the mechanism of mitophagy-inducing potential of curcumin was its unique mitochondria-targeting property, which induced a burst of SDH activity and excessive ROS production. Our data suggest that curcumin induces mitochondrial dysfunction and triggers lethal mitophagy, which synergizes with radioiodine to kill thyroid cancer cells.


Epiphytic microorganisms degrading aromatic hydrocarbons from the phyllosphere of urban woody plants.
From the leaves of three urban trees (Tilia sp., Acer sp., and Fraxinus sp.), 180 strains degrading phenanthrene, naphthalene, and salicylate were isolated by direct plating and enrichment cultures. The leaves of each tree species were characterized by a specific profile of aromatic hydrocarbon-degrading microflora. Members of the type Actinobacteria were predominant in the case of direct plating on media with phenanthrene and naphthalene. Enrichment cultures with phenanthrene and salicylate were shown to yield microbial consortia, the composition of which changed with time. Members of the type Proteobacteria were predominant in these consortia. No plasmids of polycyclic aromatic hydrocarbon degradation of the P-7 and P-9 incompatibility groups were revealed in the studied strains.


The effect of chemical blockade of PKC with Gö6976 and Gö6983 on proliferation and MAPK activity in IL-6-dependent plasmacytoma cells.
Interleukin-6 (IL-6) mediates growth of murine B9 hybridoma/plasmacytoma cells via Ras-dependent mitogen-activated protein kinase (MAPK) pathway. Preincubation of cells with selective protein kinase C (PKC) inhibitors Gö6976 and Gö6983 leads to enhancement of IL-6-induced p44/p42 MAPK activity. The basal p44/p42 MAPK activity is also stimulated in the presence of both inhibitors. On the other hand, Gö6976 completely blocks proliferation, but Gö6983 which does not inhibit PKC(mu) has no effect on the cell growth. These findings suggest that PKC(mu) is required for proliferation and other PKC isoenzymes are involved in regulation of IL-6-dependent growth of B9 cells by negative regulation of the MAPK pathway.


External drainage with an Ommaya reservoir for perioperative hydrocephalus in children with posterior fossa tumors.
This study aims to evaluate an external drainage using an Ommaya reservoir for relieving perioperative hydrocephalus and reducing postoperative complications in children with posterior fossa tumors. We retrospectively analyzed the data from 48 children with posterior fossa tumors who underwent tumor resection between May 2006 and June 2012. An Ommaya reservoir was placed in the right lateral ventricle forehead for continuous perioperative drainage of cerebrospinal fluid (CSF). Tumors were successfully removed from all patients. Intracranial infection occurred in nine patients and was controlled by antibiotic treatment. Preoperative obstruction and obstructive hydrocephalus were relieved, and the need for a shunt or endoscopic third ventriculostomy was avoided. One patient who underwent a second surgical procedure had intracranial infection, hydrocephalus, and occipital pseudomeningocele. After continuous drainage and anti-infective treatment, hydrocephalus and intracranial infection were effectively controlled. Using an Ommaya reservoir for perioperative external ventricular CSF drainage enabled tumors to be wholly and safely removed. Restoring CSF circulation provided an effective means of controlling and preventing hydrocephalus secondary to posterior fossa tumors in children.


Banking sector reactions to COVID-19: The role of bank-specific factors and government policy responses.
This paper examines the impact of bank-specific factors and variations in the context of stringency of government policy responses on bank stock returns because of the COVID-19 pandemic. A sample of 1,927 publicly listed banks from 110 countries is used for the period of the first major wave of COVID-19, that is, January to May 2020. Our findings indicate that stock returns of banks with higher capitalization and deposits, more diversification, lower non-performing loans, and larger size are more resilient to the pandemic. While banks' environment and governance scores do not have a significant impact, higher social and corporate social responsibility strategy scores intensify the negative stock price reaction to COVID-19. We further observe that the pandemic-induced reduction in bank stock prices is mitigated as the strictness of government policy responses increases, mainly through economic responses such as income support, debt and contract relief, and fiscal measures from governments.


Mechanical and Physical Properties of Two Different Resin-based Materials: A Comparative Study.
The purpose of this study was to evaluate the degree of conversion (DC) of two different resin-based composite materials (nanofill composite and ormocer) and correlate it with some mechanical properties of these two restorative materials. Two different resin-based materials (Filtek Supreme XT and Admira) were tested. A total of 30 samples of each type of selected composite were prepared. Specimens were immersed in distilled water for 24 hours. Then, the specimens were subjected to DC, hardness, and diametral tensile strength (DTS) measurements. The data obtained were tabulated for statistical analysis. The t-test was used to detect the significant difference among the variables tested in this study. Furthermore, the interrelationship between the studied parameters was investigated using a simple correlation coefficient statistical test. Statistically significant differences were observed regarding DC, hardness, and DTS. Filtek Supreme XT presented the highest values. There was a positive correlation between DC and hardness. Also there was a correlation between DC and DTS, but it was not significant. Under the tested experimental conditions, the DC of Filtek Supreme XT was higher than that of ormocer. Accordingly, Filtek Supreme XT showed better mechanical properties. Filtek Supreme XT showed superior mechanical properties. Therefore, orthodontic bracket-based composite combinations may also be expected to perform well clinically over the lifetime of a bonded orthodontic appliance.


The SPN Pediatric Nursing Excellence Model: Differentiating pediatrics.
The question of what makes an "excellent" pediatric nurse has been asked frequently by both pediatric and non-pediatric nurses for many years. Longevity in the practice setting, increased formal education in the care of children and families, positive satisfaction surveys post encounter, quantity of professional presentations and publications, and specialty certification are often listed when discussing pediatric nursing excellence. However, pediatric nursing excellence (PNE) is not well defined. Current recognition mechanisms such as clinical ladders, Magnet© and Pathways© programs, and Benner's stages of clinical competence are not specific for pediatric nursing practice. Once the characteristics of pediatric nursing excellence are determined, they can be used as the basis for identifying pediatric-specific quality indicators. In 2020, SPN initiated a project to define the construct of "pediatric nursing excellence". Two years later, SPN published its Pediatric Nursing Excellence Model, consisting of a visual depiction accompanied by definitions of 16 concepts that comprise the PNE Model. This article presents the five stages of the development process, the components of a model of pediatric nursing excellence, and the potential uses of such a model.


Structural and Comparative Analyses of Insects Suggest the Presence of an Ultra-Conserved Regulatory Element of the Genes Encoding Vacuolar-Type ATPase Subunits and Assembly Factors.
Gene and genome comparison represent an invaluable tool to identify evolutionarily conserved sequences with possible functional significance. In this work, we have analyzed orthologous genes encoding subunits and assembly factors of the V-ATPase complex, an important enzymatic complex of the vacuolar and lysosomal compartments of the eukaryotic cell with storage and recycling functions, respectively, as well as the main pump in the plasma membrane that energizes the epithelial transport in insects. This study involves 70 insect species belonging to eight insect orders. We highlighted the conservation of a short sequence in the genes encoding subunits of the V-ATPase complex and their assembly factors analyzed with respect to their exon-intron organization of those genes. This study offers the possibility to study ultra-conserved regulatory elements under an evolutionary perspective, with the aim of expanding our knowledge on the regulation of complex gene networks at the basis of organellar biogenesis and cellular organization.


On the origin of extracellular GABA collected by brain microdialysis and assayed by a simplified on-line method.
The present study describes a simplified on-line system for determination of GABA in brain dialysates. GABA was determined with an isocratic HPLC method after derivatization with o-phthaldialdehyde. One peristaltic pump was sufficient to transport both the perfusion fluid and the derivatizing reagent. The basal release of GABA was stimulated by infusion with either elevated K+ or the GABA uptake inhibitor (-)-nipecotic acid. Basal as well as stimulated GABA release were investigated for possible calcium-dependency by infusing submmolar amounts of the potent calcium antagonist cadmium. Infusion of cadmium did not modify the dialysate concentrations of GABA. In addition basal as well as nipecotic acid enhanced release of GABA dialysate concentrations were investigated for nerve-impulse dependency by infusing mumolar amounts of tetrodotoxin. No change in the GABA output was observed during infusion of TTX. From these results it is concluded that the basal as well as the nipecotic acid induced release of GABA did not fulfill the criteria for classic exocytotic release. Possible explanations for these unexpected findings are discussed.


Regional cerebral perfusion during the premonitory phase of triggered migraine: A double-blind randomized placebo-controlled functional imaging study using pseudo-continuous arterial spin labeling.
To identify changes in regional cerebral blood flow (CBF) associated with premonitory symptoms (PS) of nitroglycerin (NTG)-triggered migraine attacks. PS could provide insights into attack initiation and alterations in neuronal function prior to headache onset. We undertook a functional imaging study using a double-blind placebo-controlled randomized approach in patients with migraine who spontaneously experienced PS, and in whom PS and migraine-like headache could be induced by administration of NTG. All study visits took place in a dedicated clinical research facility housing a monitoring area with clinical beds next to a 3Tesla magnetic resonance imaging scanner. Fifty-three patients with migraine were enrolled; imaging on at least one triggered visit was obtained from 25 patients, with 21 patients completing the entire imaging protocol including a placebo visit. Whole brain CBF maps were acquired using 3D pseudo-continuous arterial spin labeling (3D pCASL). The primary outcome was that patients with migraine not taking preventive treatment (n = 12) displayed significant increases in CBF in anterior cingulate cortex, caudate, midbrain, lentiform, amygdala and hippocampus (p < 0.05 family-wise error-corrected) during NTG-induced PS. A separate region of interest analysis revealed significant CBF increases in the region of the hypothalamus (p = 0.006, effect size 0.77). Post hoc analyses revealed significant reductions in CBF over the occipital cortices in participants with a history of migraine with underlying aura (n = 14). We identified significant regional CBF changes associated with NTG-induced PS, consistent with other investigations and with novel findings, withstanding statistical comparison against placebo. These findings were not present in patients who continually took preventive medication. Additional findings were identified only in participants who experience migraine with aura. Understanding this biological and treatment-related heterogeneity is vital to evaluating functional imaging outcomes in migraine research.


Important contributions of sea-salt aerosols to atmospheric bromine cycle in the Antarctic coasts.
Polar sunrise activates reactive bromine (BrOx) cycle on the Antarctic coasts. BrOx chemistry relates to depletion of O3 and Hg in polar regions. Earlier studies have indicated "blowing snow" as a source of atmospheric BrOx. However, surface O3 depletion and BrO enhancement occurs rarely under blowing snow conditions at Syowa Station, Antarctica. Therefore, trigger processes for BrOx activation other than the heterogeneous reactions on blowing snow particles must be considered. Results of this study show that enhancement of sea-salt aerosols (SSA) and heterogeneous reactions on SSA are the main key processes for atmospheric BrOx cycle activation. Blowing snow had Br- enrichment, in contrast to strong Br- depletion in SSA. In-situ aerosol measurements and satellite BrO measurements demonstrated clearly that a BrO plume appeared simultaneously in SSA enhancement near the surface. Results show that surface O3 depletion at Syowa Station occurred in aerosol enhancement because of SSA dispersion during the polar sunrise. Amounts of depleted Br- from SSA were matched well to the tropospheric vertical column density of BrO and BrOx concentrations found in earlier work. Our results indicate that SSA enhancement by strong winds engenders activation of atmospheric BrOx cycles via heterogeneous reactions on SSA.


Acute pancreatitis-onset carcinoma in situ of the pancreas with focal fat replacement diagnosed using serial pancreatic-juice aspiration cytologic examination (SPACE).
A 59-year-old woman was admitted for acute pancreatitis. Abdominal computed tomography and magnetic resonance imaging revealed a swollen pancreatic parenchyma with dilatation of the main pancreatic duct (MPD) of the pancreas tail, which was separated from the normal pancreas body side by a locally atrophic part of the pancreas. Magnetic resonance cholangiopancreatography showed MPD stricture in the pancreas tail with dilatation of the upstream MPD. Endoscopic ultrasonography revealed that the MPD stricture of the pancreas tail was surrounded by a blurred and hypoechoic area. Endoscopic retrograde cholangiopancreatography was performed for serial pancreatic-juice aspiration cytologic examination (SPACE). The result indicated adenocarcinoma. Distal pancreatectomy was performed, and the histopathological examination showed high-grade PanIN (carcinoma in situ of the pancreatic duct) of the pancreas tail with atrophy and fibrosis of the pancreatic parenchyma, and local fat replacement adjacent to the lesion. The final histopathological diagnosis was carcinoma in situ of the pancreatic duct of the pancreas tail. Acute pancreatitis and local fatty change of the pancreatic parenchyma with MPD stricture are important clinical manifestations of pancreatic carcinoma in situ (PCIS) and performing SPACE in cases of MPD stricture without a recognizable mass is preferable for a diagnosis of PCIS.


Oxidized cellulose--survey of the most recent achievements.
The functionalization and particularly the oxidation of cellulose is an intriguing and challenging topic due to the presence of multiple reactive sites, which can undergo specific reactions. The variety of the oxidizing agents used to improve the selectivity and yields of these transformations is illustrated by the steadily growing of the number of publications and patents reported. This paper is focused on the most selective agents for cellulose oxidations, i.e., sodium periodate and stable or non persistent nitroxyl radicals, emphasizing on the most recent developments reported so far.


Visfatin enhances the production of cathelicidin antimicrobial peptide, human β-defensin-2, human β-defensin-3, and S100A7 in human keratinocytes and their orthologs in murine imiquimod-induced psoriatic skin.
Psoriasis, a chronic inflammatory dermatosis, is frequently associated with metabolic disorders, suggesting that adipokines are involved in its pathogenesis. We recently reported that the adipokine visfatin activates NF-κB and STAT3 in keratinocytes. Antimicrobial peptide expression is enhanced in psoriatic lesions and may promote disease development. Here, we investigated the effects of visfatin on antimicrobial peptide expression. In vitro, visfatin enhanced basal and tumor necrosis factor-α (TNF-α)-induced mRNA expression and secretion of cathelicidin antimicrobial peptide (CAMP), and enhanced TNF-α-induced human β-defensin-2 (hBD-2), hBD-3, and S100A7 mRNA expression and secretion in human keratinocytes. siRNAs targeting CCAAT/enhancer-binding protein-α (C/EBPα) suppressed visfatin-induced and visfatin plus TNF-α-induced CAMP production. siRNAs targeting NF-κB p65 and STAT3 suppressed visfatin plus TNF-α-induced hBD-2 and S100A7 production. siRNAs targeting c-Jun and STAT3 suppressed visfatin plus TNF-α-induced hBD-3 production. Visfatin and/or TNF-α enhanced C/EBP transcriptional activity and C/EBPα phosphorylation, which were suppressed by p38 mitogen-activated protein kinase (MAPK) inhibition. Visfatin and/or TNF-α induced p38 MAPK phosphorylation. Visfatin increased mRNA and protein expression of CAMP, hBD-2, hBD-3, and S100A7 orthologs in murine imiquimod-treated skin, mimicking psoriasis. In conclusion, visfatin enhances CAMP, hBD-2, hBD-3, and S100A7 production in human keratinocytes and their orthologs in murine imiquimod-treated psoriatic skin. Visfatin may potentiate the development of psoriasis via antimicrobial peptides.


Causal attribution fractions, and the attribution of smoking and BMI to the landscape of disease incidence in UK Biobank.
Unlike conventional epidemiological studies that use observational data to estimate "associations" between risk factors and disease, the science of causal inference has identified situations where causal estimates can be made from observational data, using results such as the "backdoor criteria". Here these results are combined with established epidemiological methods, to calculate simple population attribution fractions that estimate the causal influence of risk factors on disease incidence, and can be estimated using conventional proportional hazards methods. A counterfactual argument gives an attribution fraction for individuals. Causally meaningful attribution fractions cannot be constructed for all risk factors or confounders, but they can for the important established risk factors of smoking and body mass index (BMI). Using the new results, the causal attribution of smoking and BMI to the incidence of 226 diseases in the UK Biobank are estimated, and summarised in terms of disease chapters from the International Classification of Diseases (ICD-10). The diseases most strongly attributed to smoking and BMI are identified, finding 11 with attribution fractions greater than 0.5, and a small number with protective associations. The results provide new tools to quantify the causal influence of risk factors such as smoking and BMI on disease, and survey the causal influence of smoking and BMI on the landscape of disease incidence in the UK Biobank population.


All-optical switching of the transmission of electromagnetic radiation through subwavelength apertures.
Unprecedented optical control of the surface plasmon polariton assisted transmission of terahertz radiation through subwavelength apertures is rendered possible by carrier-induced changes to the dielectric properties of a semiconductor grating. Although the study presented is static, the extension of our approach to dynamic switching and tuning is deemed straightforward, opening the way for the realization of ultrafast surface plasmon based devices.


Monoclonal antibody to human endothelial cell surface internalization and liposome delivery in cell culture.
A monoclonal antibody (mAb), E25, is described that binds to the surface of cultured human endothelial cells. Upon binding E25 is rapidly internalized and digested intracellularly. Selective liposome targeting to the surface of the cells is performed using a biotinylated E25 antibody and an avidin-biotin system. Up to 30% of the cell-adherent liposomal lipid is internalized.


Treatment of chronic prostatitis: intraprostatic antibiotic injections under echography control.
We treated 51 patients diagnosed as having chronic bacterial prostatitis (gram-negative) with 2 ml. intraprostatic amikacin (500 mg.) or tobramycin (100 mg.) weekly for 2 to 4 weeks. Administration was perineal with echographic control and injection was done in the echogenic zone or external gland. In each case the diagnosis was obtained by fractioned microbiological study via the method of Meares and Stamey. This test was repeated 4, 12 and 24 weeks after the end of treatment. Of the patients 25 (49 per cent) were cured microbiologically, 11 (21.5 per cent) were cured after a second cycle of treatment and the remaining 15 (29.4 per cent) failed to respond. The clinical cure rate was 43.1 per cent and 41.1 per cent of the patients were improved. After 6 months 5 patients had relapse and 1 had reinfection. No differences were observed with both antimicrobials. The microbiological cure indexes of 70.5 and 58.8 per cent after 3 and 6 months, respectively, compared favorably with that obtained by oral therapy with antimicrobials that reach effective levels in the prostatic fluid. Transitory post-injection hemospermia was observed in 11 patients. Together with pain during or after injection (8 and 5 patients, respectively), these were the sole adverse effects observed with this therapy.


Examination of medical professions for counseling on medication adherence.
The abilities of 68 professional staff members (physicians, physician assistants, dietitians, nurses, and counselors) from 12 clinics of the Coronary Primary Prevention Trial of the Lipid Research Clinics Program in 28 specific skills fundamental to interviewing and counseling for medication adherence were examined. Each staff member was provided with confidential data regarding his or her abilities, and each clinic's trial director received the group data for his or her staff's possession and use of these skills. Analyses of trial-wide data showed substantial differences among clinics in possession and use of the skills, with overall greater strength in interviewing skills, as compared with assessment and counseling skills. No professional group consistently possessed most or fewest of these skills. It is suggested that trained non-physician personnel could be used to complement physician efforts to counsel patients for medication adherence.


Phospholysine phosphohistidine inorganic pyrophosphate phosphatase suppresses human esophageal cancer cell growth by inducing mitotic catastrophe through the P27/cyclin A/CDK2 signaling pathway.
Esophageal cancer (ESCA) is a global dead malignancy with poor prognosis. However, its underlying molecular mechanism remains to be elucidated. Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) has been reported as a tumor suppressor in multisystem cancer but its function in ESCA has not been reported. We analyzed LHPP expression between normal and tumor tissues of ESCA patients and performed LHPP overexpression on the ESCA cells KYSE-150 (K150). We did not observe significant differences in the expression level of LHPP between ESCA and normal tissue, and noticed that LHPP expression was not related to ESCA patient survival rate. However, increased expression of LHPP in K150 cells induced mitochondrial dysfunction, inhibited cell proliferation, migration, and cell cycle, and simultaneously increased cell apoptosis. Besides, we found that K150 cells underwent mitotic catastrophe after overexpressing LHPP, which may be regulated through the P27/cyclin A/cdk2 signaling pathway. Although the expression of LHPP may not be related to the progression and prognosis of ESCA, mitotic catastrophe, a new mechanism of tumor suppressor function of LHPP was found after overexpressing LHPP in ESCA cells. DATA AVAILABILITY: The data used to support the findings of this study are included within the article.


Effect of hydroalcoholic extract from Copaifera langsdorffii leaves on urolithiasis induced in rats.
Copaifera langsdorffii Desf. commonly known as "copaíba", produce a commercially valuable oil-resin that is extensively used in folk medicine for anti-inflammatory, antimicrobial and antiseptic purposes. We have found the hydroalcoholic extract of this plant leaf has the potential to treat urolithiasis, a problem affecting ~7% of the population. To isolate the functional compounds C. langsdorffii leaves were dried, ground, and macerated in a hydroalcoholic solution 7:3 to produce a 16.8% crude extract after solvent elimination. Urolithiasis was induced by introduction of a calcium oxalate pellet (CaOx) into the bladders of adult male Wistar rats. The treated groups received the crude extract by oral gavage at 20 mg/kg body weight daily for 18 days. Extract treatment started 30 days after CaOx seed implantation. To monitor renal function sodium, potassium and creatinine concentrations were analyzed in urine and plasma, and were found to be in the normal range. Analyses of pH, magnesium, phosphate, calcium, uric acid, oxalate and citrate levels were evaluated to determine whether the C. langsdorffii extract may function as a stone formation prevention agent. The HPLC analysis of the extract identified flavonoids quercitrin and afzelin as the major components. Animals treated with C. langsdorffii have increased levels of magnesium and decreased levels of uric acid in urinary excretions. Treated animals have a significant decrease in the mean number of calculi and a reduction in calculi mass. Calculi taken from extract treated animals were more brittle and fragile than calculi from untreated animals. Moreover, breaking calculi from untreated animals required twice the amount of pressure as calculi from treated animals (6.90 ± 3.45 vs. 3.00 ± 1.51). The extract is rich in flavonoid heterosides and other phenolic compounds. Therefore, we hypothesize this class of compounds might contribute significantly to the observed activity.


Antagonistic effect of flavonoids on NSC-741909-mediated antitumor activity via scavenging of reactive oxygen species.
NSC-741909 (1-[(4-chlorophenyl)methyl]-1H-Indole-3-methanol) is a novel anticancer agent that is highly active against several NCI-60 cancer cell lines. This agent induces sustained activation of mitogen-activated protein kinases (MAPK), including JNK and p38 MAP kinases. However, the mechanisms of its selective antitumor activity in some cancer cell lines remain unknown. We tested the combined effects of NSC-741909 and several kinase inhibitors that target the Raf/MEK/ERK1/2 or PI3K/AKT pathways in two sensitive lung cancer cells. We found that PD98059 (2'-amino-3'-methoxyflavone), a flavone derivative and a selective MEK inhibitor, can dramatically block the cell killing effect of NSC-741909. To determine whether this inhibitory effect is associated with MEK inhibition or other mechanisms, we evaluated the effects of other MEK inhibitors with different chemical structures and flavone derivatives that do not have an effect on MEK. We found that several flavonoids can markedly block NSC-741909-induced apoptosis and JNK activation in a time-dependent manner, regardless of whether they inhibit MEK or not. In contrast, NSC-741909-induced JNK activation and apoptosis were not blocked by other MEK-specific inhibitors U0126 and CI1040. Our results also showed that NSC-741909 induced a dramatic increase of reactive oxygen species in sensitive cells and that flavonoids effectively blocked the NSC-741909-induced reactive oxygen species production which are associated with flavonoids' antagonistic effects on NSC-741909-induced JNK activation and apoptosis. Those results demonstrated that flavonoids-mediated antagonist effect is through scavenging of reactive oxygen species. Our results may have implication on the design of clinical evaluation of antitumor activity of NSC-741909 or its analogues.


Neonatal sepsis in alloimmune hemolytic disease of the fetus and newborn: A retrospective cohort study of 260 neonates.
Among neonates with hemolytic disease of the fetus and newborn (HDFN), we aimed to describe the frequency of central-line use, indications for insertion, and incidence of confirmed and suspected sepsis, including antibiotic treatment over a 10-year surveillance period. All neonates with HDFN admitted to our neonatal intensive care unit between January 2012 and December 2021 were included in this retrospective, cohort study. Annual proportions of infants with a central-line and central-line-associated bloodstream infection (CLABSI) rates (per 1000 central-line days and per 100 infants) were evaluated. Numbers of confirmed and suspected early- and late-onset sepsis episodes were assessed over the entire study period. Of the 260 included infants, 25 (9.6%) were evaluated for suspected sepsis, with 16 (6.2%) having ≥1 confirmed sepsis episode. A total of 123 central-lines were placed in 98 (37.7%) neonates, with impending exchange transfusion (ET) being the most frequent indication. Of the 34 (34.7%) neonates in whom a central-line was placed due to impending ET, 11 (32.4%) received no ET. Overall CLABSI incidence was 13.58 per 1000 central-line days. Neonates with a central-line had a higher risk for confirmed late-onset infection (RR 1.11, 95% CI: 1.04-1.20) and sepsis work-up (RR 1.10, 95% CI: 1.03-1.17) compared to infants without a central-line. Sepsis incidence among neonates with HDFN remains high, in particular in those with a central-line. Considering the substantial proportion of neonates with a central-line without eventual ET, central-line placement should be delayed until the likelihood of ET is high.


Coordination, cooperation, and creativity within harm reduction networks in Iran: COVID-19 prevention and control among people who use drugs.
An unprecedented public health crisis confronts the world. Iran is among the hardest-hit countries, where effects of the COVID-19 pandemic are stretched across society and felt by the most marginalised people. Among people who use drugs, a comprehensive response to the crisis calls for broad collaboration, coordination, and creativity involving multiple government and non-government organisations. This commentary provides early insights into an unfolding experience, demonstrating the operational and policy impact of an initiative, bringing together a diverse array of harm reduction stakeholders to address the pandemic. In the context of lived experiences of social and economic marginalization, this initiative intends to lead efforts in developing an equitable response to the COVID-19 pandemic.


Induction of a brainstem correlate of conditioned taste aversion expression: role of the pontine parabrachial nucleus.
Increases in Fos-like immunoreactivity (FLI) in the intermediate division of the nucleus of the solitary tract (iNTS) are seen following the expression of a conditioned taste aversion (CTA). In studies limited to behavioral assessment, the pontine parabrachial nucleus (PBN) has been demonstrated to play a critical role in the acquisition, but not the expression, of CTAs. To better define the role of the PBN in taste aversion learning, the present study examined the effects of PBN lesions on FLI in iNTS in animals with lesions placed either before or after CTA training. As is the case with behavioral expression of a CTA, timing of PBN lesions was found to be critical. Lesions placed prior to conditioning blocked evidence of conditioning, including both taste rejection and FLI in iNTS. Lesions placed after conditioning, but before testing, did not interfere with either taste rejection or FLI. These results support and extend prior claims that PBN is critical for CTA acquisition but not expression. They also demonstrate that input from PBN to iNTS is not necessary for the FLI seen there during CTA expression.


Renal effects of losartan and amlodipine in hypertensive patients with non-diabetic nephropathy.
The objective of this study was to examine the effects of angiotensin II receptor blocker losartan versus the calcium channel blocker amlodipine on proteinuria, renal haemodynamics, glomerular sieving and tubular function in hypertensive patients with non-diabetic nephropathy. The study design was a prospective, double blind, placebo controlled, randomized crossover trial with amlodipine and losartan. Renal parameters were measured at baseline and at the end of each 4-week active treatment period. Fifteen patients with a diagnosis of non-diabetic renal disease and hypertension were included. Mean arterial blood pressure decreased from 123+/-13 mmHg at baseline to 113+/-10 mmHg (P<0.01) on losartan and to 114+/-10 mmHg on amlodipine (P<0.01). Urinary albumin excretion significantly decreased from 3510+/-2586 mg/24 h at baseline to 2684+/-2051 mg/24 h (P<0.01) on losartan and increased non-significantly to 3748+/-3355 mg/24 h on amlodipine. Filtration fraction significantly decreased from a baseline value of 22.8+/-9.3% to 21.2+/-10.2% (P<0.05) on losartan and increased to 23.6+/-8.9% (ns) on amlodipine. Either drug did not significantly alter glomerular sieving of neutral dextrans. Our results demonstrate that losartan, but not amlodipine, decreased albumin excretion in hypertensive patients with non-diabetic nephropathy.


Molecular modeling of the bacterial outer membrane receptor energizer, ExbBD/TonB, based on homology with the flagellar motor, MotAB.
The MotA/MotB proteins serve as the motor that drives bacterial flagellar rotation in response to the proton motive force (pmf). They have been shown to comprise a transmembrane proton pathway. The ExbB/ExbD/TonB protein complex serves to energize transport of iron siderophores and vitamin B12 across the outer membrane of the Gram-negative bacterial cell using the pmf. These two protein complexes have the same topology and are homologous. Based on molecular data for the MotA/MotB proteins, we propose simple three-dimensional channel structures for both MotA/MotB and ExbB/ExbD/TonB using modeling methods. Features of the derived channels are discussed, and two possible proton transfer pathways for the ExbBD/TonB system are proposed. These analyses provide a guide for molecular studies aimed at elucidating the mechanism by which chemiosmotic energy can be transferred either between two adjacent membranes to energize outer membrane transport or to the bacterial flagellum to generate torque.


Single-port inflatable mediastinoscopic esophagectomy is a cure for esophageal cancer patients: Case report.
It is often difficult to perform transthoracic esophagectomy (TTE) in patients with chest deformities, as these patients may be lost to surgery for non-oncological reasons. In this case, we had a patient with esophageal squamous cell carcinoma (ESCC) who was not suitable for TTE because of extensive thoracic adhesions caused by the left pneumonectomy 8 years ago. ESCC. Based on Professor Fujiwara's surgical method, we further improved it by proposing a single-port inflatable mediastinoscopy combined with laparoscopic-assisted esophagectomy. At the time of this writing, computed tomography and gastroscopy revealed no stenosis of anastomosis, and no evidence of disease recurrence. To the best of our knowledge, the present case is the first single-port inflatable mediastinoscopic esophagectomy performed on a patient undergoing pneumonectomy.


Where does fear originate in the brain? A coordinate-based meta-analysis of explicit and implicit fear processing.
Processing of fear is of crucial importance for human survival and it can generally occur at explicit and implicit conditions. It is worth noting that explicit and implicit fear processing produces different behavioral and neurophysiological outcomes. The present study capitalizes on the Activation Likelihood Estimation (ALE) method of meta-analysis to identify: (a) the "core" network of fear processing in healthy individuals; (b) common and specific neural activations associated with explicit and implicit processing of fear. Following PRISMA guidelines, a total of 92 fMRI and PET studies were included in the meta-analysis. The overall analysis show that the core fear network comprises the amygdala, pulvinar, and fronto-occipital regions. Both implicit and explicit fear processing activated amygdala, declive, fusiform gyrus, and middle frontal gyrus, suggesting that these two types of fear processing share a common neural substrate. Explicit fear processing elicited more activations at the pulvinar and parahippocampal gyrus, suggesting visual attention/orientation and contextual association play important roles during explicit fear processing. In contrast, implicit fear processing elicited more activations at the cerebellum-amygdala-cortical pathway, indicating an 'alarm' system underlying implicit fear processing. These findings have shed light on the neural mechanism underlying fear processing at different levels of awareness.


Ordered assemblies of myosin minifilaments.
Electron microscopic observations of negatively stained myosin minifilaments in a solution containing 10 mM-citrate buffer (pH 8.0), 4 mM-MgCl2 reveal ordered assemblies. They reveal bundles of parallel minifilaments of about 330 nm in length, aggregated into periodic linear and hexagonal structures. These structures are formed by means of interaction between myosin heads, arranged at the ends of minifilament bundles. The addition of 1 mM-ATP to the above solution causes dissociation of minifilament bundles into individual minifilaments without preventing the latter from association into linear "end-to-end" assemblies. Phosphorylation of myosin light chains does not exert any noticeable effect on the structure of the ordered minifilament assemblies but significantly increases their quantity. The interaction between minifilaments observed by us should be taken into consideration in studies on the properties of myosin which make use of minifilament systems.


Developing medical student competence in lifelong learning: the contract learning approach.
How contract learning may be used in the introduction to clinical medicine is described, with the goal to develop and enhance self-directed learning skills and attitudes of first- and second-year medical students. Essential tasks associated with successful self-directed learning are cited, and the contract method is described as a means for providing medical students with the opportunity to practice these tasks in the study of gerontology. The procedures followed in the implementation of the contract learning method are described, and its impact on both need and to continue learning about ageing and skills in directing independent learning projects are analysed and discussed. In addition, the implications of early preparation for doctor's lifelong learning are discussed.


Spatiotemporal variations of water quality and their driving forces in the Yangtze River Basin, China, from 2008 to 2020 based on multi-statistical analyses.
Water quality deterioration is a prominent issue threatening water security worldwide. As the largest river in China, the Yangtze River Basin is facing severe water pollution due to intense human activities. Analyzing water quality trends and identifying the corresponding driver factors are important components of sustainable water quality management. Thus, spatiotemporal characteristics of the water quality from 2008 to 2020 were analyzed by using a Mann-Kendall test and rescaled range analysis (R/S). In addition, multi-statistical analyses were used to determine the main driving factors of variation in the permanganate index (CODMn), ammonia nitrogen (NH3-N) concentration, and total phosphorus (TP) concentration. The results showed that the mean concentrations of NH3-N and TP decreased from 0.31 to 0.16 mg/L and 0.16 to 0.07 mg/L, respectively, from 2008 to 2020, indicating that the water quality improved during this period. However, the concentration of CODMn did not reduce remarkably. Based on R/S analysis, the NH3-N concentration was predicted to continue to decrease from 2020 to 2033, whereas the CODMn concentration was forecast to increase, highlighting an issue of great concern. In terms of spatial distribution, water quality in the upstream was better than that of the mid-downstream. Multi-statistical analyses revealed that the temporal variation in water quality was predominantly influenced by tertiary industry (TI), the nitrogen fertilizer application rate (N-FAR), the phosphate fertilizer application rate (P-FAR), and the irrigation area of arable land (IAAL), with contribution rates of 15.92%, 14.65%, 3.46%, and 2.84%, respectively. The spatial distribution of CODMn was mainly influenced by TI, whereas that of TP was primarily determined by anthropogenic activity factors (e.g., N-FAR, P-FAR). This study provides deep insight into water quality evolution in the Yangtze River Basin that can guide water quality management in this region.


Metal-organic framework grown in situ on chitosan microspheres as robust host of palladium for heterogeneous catalysis: Suzuki reaction and the p-nitrophenol reduction.
In this study, the metal-organic framework ZIF-8 has been successfully planted on the surface of chitosan microspheres (CS/PDA@ZIF-8) using polydopamine as connecting material for the first time, which avoids the use of expensive, non-renewable, and non-biodegradable polystyrene microspheres commonly used as templates to prepare core-shell structures. Moreover, the metal-organic framework ZIF-8 was prepared specially by three different methods and all characterized by SEM, TEM, and BET, and the ZIF-8 shell prepared at room temperature presents a regular morphology, uniform size, large specific surface area (353.1 m2/g) than the shells prepared by the other methods including. The CS/PDA@ZIF-825@Pd with high catalytic activity and high stability was especially prepared by encapsulating Pd nanoparticles into the pores of CS/PDA@ZIF-825. Notably, the fabricated catalyst performed well in an array of reactions, for example the Kapp value of the p-nitrophenol reduction reaction reached 0.0426 s-1, and the TOF of the Suzuki coupling reaction reached 128 h-1. In addition, the ZIF-67, UiO-66, UiO-66-NH2, HKUST-1, and NH2-MIL-53(Al) were also grown on chitosan microcapsules successively to prepare the core-shell microspheres, which prove the universal applicability of this strategy. And beyond that, the introduction of chitosan microspheres endows the material with biodegradable properties and excellent recycling properties.


Editorial to Special Issue-Research on Isolation and Intelligent Detection Methods of Foodborne Pathogens.
Foodborne illnesses pose a significant threat worldwide to public health [...].


Oncoapoptotic signaling and deregulated target genes in cancers: special reference to oral cancer.
Cancer is a class of diseases characterized by uncontrolled cell growth. The development of cancer takes place in a multi-step process during which cells acquire a series of mutations that eventually lead to unrestrained cell growth and division, inhibition of cell differentiation, and evasion of cell death. Dysregulation of oncoapoptotic genes, growth factors, receptors and their downstream signaling pathway components represent a central driving force in tumor development. The detailed studies of signal transduction pathways for mechanisms of cell growth and apoptosis have significantly advanced our understanding of human cancers, subsequently leading to more effective treatments. Oral squamous cell carcinoma represents a classic example of multi-stage carcinogenesis. It gradually evolves through transitional precursor lesions from normal epithelium to a full-blown metastatic phenotype. Genetic alterations in many genes encoding crucial proteins, which regulate cell proliferation, differentiation, survival and apoptosis, have been implicated in oral cancer. As like other solid tumors, in oral cancer these genes include the ones coding for cell cycle regulators or oncoproteins (e.g. Ras, Myc, cyclins, CDKs, and CKIs), tumor suppressors (e.g. p53 and pRb), pro-survival proteins (e.g. telomerase, growth factors or their receptors), anti-apoptotic proteins (e.g. Bcl2 family, IAPs, and NF-kB), pro-apoptotic proteins (e.g. Bax and BH-3 family, Fas, TNF-R, and caspases), and the genes encoding key transcription factors or elements for signal transduction leading to cell growth and apoptosis. Here we discuss the current knowledge of oncoapoptotic regulation in human cancers with special reference to oral cancers.


Investigations of the possible pharmacological effects of organotin(II) complexes.
Antitumour, antifertility and histopathological investigations were carried out on male rats by the use of organotin complexes. The organotin complexes were synthesized by the alkylation of [Sn(TAML(n))Cl(2)] (n=1-4 and TAML(n) represents the tetraazamacrocyclic ligands) in the presence of CH(3)I or C(2)H(5)Br. The structures of all the complexes have been established on the basis of elemental analyses, conductivity measurements, IR, (1)H NMR, (13)C NMR, (119)Sn NMR and X-ray spectral data. The antitumour effect of the compounds was examined on swiss mice. The results obtained clearly indicated that the compounds, [C(2)H(5)Sn(TAML(3))C(5)H(5)N] and [C(2)H(5)Sn(TAML(4))C(5)H(5)N] display effective antitumour activity. The emphasis has been given on in vivo study on male albino rats (Rattus norvegicus) by performing serum analyses, blood analyses and fertility test.


'M' cells in the follicle-associated epithelium of the human colon.
The morphology of the epithelium overlying human colonic mucosal lymphoid follicles has been studied by electron microscopy. Epithelial crypts stop at the edge of the follicle and the centre is covered by a single layer of enterocytes. Numerous lymphocytes and, occasionally, other mononuclear cells, are associated with these enterocytes. The lymphocytes are situated in the intercellular spaces, invaginate the lateral cell wall and ultimately appear to be completely surrounded by the enterocyte. When the lymphocyte is near the centre of the enterocyte there is usually little change in enterocyte morphology, but when the lymphocyte is near the apical surface of the enterocyte, the latter closely resembles the membranous epithelial cells ('M' cells) of human small intestine. It is probable that, as with the 'M' cells in the small intestine, these colonic 'M' cells have an antigen sampling function. Their presence may explain the localization of the early lesions of some colonic inflammatory diseases, including Crohn's disease. They may also provide a portal of entry for some rectally-transmitted viral infections.


Associations of short- and long-term mortality with admission blood pressure in Chinese patients with different heart failure subtypes.
It remains unknown whether systolic (SBP) and diastolic (DBP) pressure on admission are associated with short- and long-term mortality in Chinese patients with heart failure with preserved (HFpEF), mildly reduced (HFmrEF), and reduced (HFrEF) ejection fraction. In 2706 HF patients (39.1% women; mean age, 68.8 years), we assessed the risk of 30-day, 1-year, and long-term (> 1 year) mortality with 1-SD increment in SBP and DBP, using multivariable logistic and Cox regression, respectively. During a median follow-up of 4.1 years, 1341 patients died. The 30-day, 1-year, and long-term mortality were 3.5%, 16.7%, and 39.4%, respectively. In multivariable-adjusted analyses additionally accounted for DBP or SBP, a higher SBP conferred a higher risk of long-term mortality (hazard ratio, 1.11; 95% CI, 1.02-1.22; p = .017) and a lower DBP was associated with a higher risk of all types of mortality (p ≤ .011) in all HF patients. Independent of potential confounders including DBP or SBP, in patients with HFpEF, higher SBP and lower DBP levels predicted a higher risk of long-term mortality with hazard ratios amounting to 1.16 (95% CI, 1.04-1.29; p = .007) and .89 (95% CI, .80-.99; p = .028), respectively. In patients with HFmrEF and HFrEF, irrespective of adjustments of potential confounders, DBP was associated with 1-year mortality with odds ratios ranging from .49 to .62 (p ≤ .006). In conclusion, lower DBP and higher SBP levels on admission were associated with a higher risk of different types of all-cause mortality in Chinese patients with different HF subtypes. Our observations highlight that admission BP may help to improve risk stratification.


Nerve growth factor promotes development of the rat septo-hippocampal cholinergic projection in vitro.
There is now widespread evidence indicating that nerve growth factor (NGF) is involved in the function of central cholinergic neurons. Its possible role in the establishment of cholinergic fiber connectivities was studied in co-cultures of rat septum and hippocampus. Application of 100 ng/ml NGF greatly increased the number of acetylcholinesterase (AChE)-positive fibers which invaded the hippocampal slices, an effect which was accompanied by a more than 6-fold elevation of the two major cholinergic enzymes, choline acetyltransferase and AChE. In contrast, application of anti-NGF antiserum, but not a non-immune serum, reduced the number of AChE-positive fibers which grew into and remained within the hippocampal slices. Since no diffuse outgrowth of AChE-positive fibers from the septum was observed following application of NGF, these results suggest that NGF plays a role in the stabilization and long-term maintenance of the cholinergic septo-hippocampal projection in vitro.


[Postop complications of perforative ulcer surgery].
Of 342 patients operated on for gastroduodenal perforative ulcer the complications have occurred in 63 (18.4%) and a progressive peritonitis in particular--in 45 (71.4%). In 4 (2.8%) of patients a peritonitis progress was noted after truncal vagotomy and ulcer excision conduction without the infection-toxical shock signs.


Concentration and temperature dependence of viscosity of uranium solutions in H2O and 3 mol/L HNO3.
Viscosities of uranium solutions in H(2)O and 3 mol/L HNO(3) medium were measured by Ubbelhode flow viscometer in the concentration range of 0.5%-3.0% from 10 degrees C to 30 degrees C at 5 degrees C interval. Viscosity data were interpreted in terms of an empirical equation; eta =a(o)exp(b(o)M+c(o)M(2)). Values of coefficients a(o), b(o) and c(o) were calculated for all the three systems studied. Flow activation energies and thermodynamic parameters were also evaluated.


The changing pattern of bioaerosol characteristics, source and risk under diversity brush aerator speed.
Bioaerosols containing pathogens released from wastewater treatment plants (WWTP) may pose potential health risks to workers on-site and residents downwind. In this study, sampling points were set up in the wastewater treatment facility to investigate the generation pattern of bioaerosols in the aeration tank section. High-throughput sequencing was utilized to assay the intestinal bacteria population, while the health risks associated with airborne bacteria were estimated based on average daily dose rates. The contribution of wastewater to bioaerosols was evaluated using the traceability analysis. As the rotational speed increased from 200 rpm to 800 rpm, the concentration of culturable bacteria increased from 397 CFU/m3 to 1611 CFU/m3, the proportion of bacteria attached to particles with an aerodynamic diameter larger than 4.7 µm increased from 30.41% to 48.44%, and the Shannon index of air samples increased from 1.032485 to 1.282065. Microbial composition, sources, and health risks of bioaerosols also changed as the rotational speed increased. The results showed that the predominant bacteria in the air at 200 rpm were Bacillus (78.78%), Paenibacillus (11.77%) and Lysinibacillus (1.40%). When the rotating speed reached 800 rpm, the dominant bacteria became Bacillus (55.50%), Acinetobacter (31.01%), and Paenarthrobacter (13.17%). The contribution of the wastewater to bioaerosols increased from 46.49% to 65.10%, in which surface water was the main source of bioaerosols (34.64% on average). Although the contribution of bottom water was lower than that of surface water, its contribution increased more, from 15.36% to 29.31%. The health risk of bioaerosols was 1.28 × 10-2 on average, which increased with the increase of rotational speed. At the same exposure concentration, children (2.31 × 10-2) have a higher exposure risk than adults (7.67 × 10-3). This study is aimed at exploring the variation law of bioaerosols discharged from WWTP with oxidation ditch process and providing preliminary data for reducing its risk.


Experience with the management of thromboembolism in patients with spinal cord injury: Part I. Incidence, diagnosis and role of some risk factors.
Fifty acute SCI patients are reviewed retrospectively for incidence of deep vein thrombosis and pulmonary embolism and the problems encountered in the diagnosis. The possible role of some risk factors in triggering thromboembolism and the consequent implications in anticoagulant therapy are discussed.


Updates in Benign Lesions of the Genitourinary Tract.
The genitourinary tract is a common site for new cancer diagnosis, particularly for men. Therefore, cancer-containing specimens are very common in surgical pathology practice. However, many benign neoplasms and nonneoplastic, reactive, and inflammatory processes in the genitourinary tract may mimic or cause differential diagnostic challenges with malignancies. Emerging clinicopathologic, immunohistochemical, and molecular characteristics have shed light on the pathogenesis and differential diagnosis of these lesions. This review addresses differential diagnostic challenges related to benign genitourinary tract lesions in the kidney, urinary bladder, prostate, and testis, with emphasis on recent advances in knowledge and areas most common in diagnostic practice.


Zuogui Wan improves spermatogenesis of GC1-spg cells through modulating AR-related pathways.
Zuogui Wan (ZGW) is a common prescription medication used in traditional Chinese medicine (TCM) to significantly improve the sperm quality and treat male infertility. This study evaluated the repair effect of ZGW and Levocarnitine (LEV) on GC1-spg cell injury induced by Glucosides of Tripterygium WilforDII Hook (GTW). The results showed that the ultrastructure and apoptosis rate of GC1- spg cells in LEV and ZGW group were considerably better than GTW. The transcriptional and translational level of CYP1A1, CYP17A1, androgen receptor (AR), SRD5A2 and proliferating cell nuclear antigen (PCNA) in GC-1spg cells of the LEV group were considerably elevated than GTW group (p < 0.05 or 0.01). Furthermore, the transcriptional and translational levels of CYP19A1, CYP17A1, AR, SRD5A2 and PCNA in GC-1spg cells in ZGW group were found to be considerably elevated than the LEV group (p < 0.05 or 0.01). The findings indicate that ZGW and LEV could increase the expression of PCNA, CYP17A1, CYP19A1, SRD5A2 and AR at transcriptional and translational levels, inhibit GC-1spg cell apoptosis and promoting cell proliferation, and the effect of ZGW was found to be significantly better than that of LEV.


Prevalence and associated factors of hypnotics dependence among Japanese outpatients with psychiatric disorders.
This study aimed to investigate the prevalence of the dependence for benzodiazepine or their agonist (BZDs) hypnotics, as well as factors associated with this dependence among Japanese psychiatric outpatients. One thousand and forty-three patients in the psychiatric outpatient clinic of Tokyo Medical University Hospital receiving treatment with BZDs hypnotics were analyzed. The subjects answered questionnaires including demographic variables, subjective sleep difficulty assessed by the Pittsburg Sleep Quality Index (PSQI), duration of hypnotics medication, dose of diazepam equivalent BZDs hypnotics, the presence or absence of subjective side effects due to BZDs hypnotics (dizziness, fatigue, daytime sleepiness, amnesia, and headache), and dependency assessed by the Dependency 2-A (D 2-A) score. Subjects with a D 2-A score ≥10 were considered as having BZDs hypnotics dependence, and the variables associated with the presence of dependence were examined using logistic regression analyses. Eighty-two out of the 1043 subjects (7.9%) were determined to have BZDs hypnotics dependence. Compared with the non-dependence group, the dependence group had a significantly higher proportion of positive respondents for all the side effects. Multiple logistic regression analyses showed that the dependence was significantly associated with younger age, higher total PSQI score, and higher daily dose of BZDs hypnotics. Younger age, higher total PSQI score, and higher dose may be associated with BZDs hypnotics dependence. The finding that patients with BZDs hypnotics dependence frequently suffered from subjective side effects and had greater sleep difficulty encourages the establishment of alternative treatments for patients with insomnia symptoms refractory to BZDs hypnotics treatment.


[Social and professional effects of hip prosthetic replacment on people under 50 years of age].
Although total hip prosthetic replacement is a common surgical procedure, it is not without social and professional consequences. In a certain number of cases, return to occupational activities is not possible. In others, it is difficult. Long-term work break repercussions can be major as they often go together with financial difficulties. The medical counsultant and the occupational doctor will have an important role to play at the time of the return to occupational activities or to determine the conditions of workplace adaptation or a vocational training program.Functional recovery after insertion of total hip prosthesis observes precise rules of articular mobilization, weight bearing and muscular strengthening.In the young patient, before 50 years old, objectives will be more accurate and progress not only will concern recovery of daily living, walking and do-it-yourself activities but also return to sports, play and occupational activities. Not only will reactivation be physical, muscular and articular but also behavioral and psychological.Disease and its consequences, surgery in particular, cause a psychological and a physical aggression which modifies the patient's self-concept. • Vulnerability and plastic wrong (limping, modifications of gesture and sports performanee as well as modifications of the living conditions). The patient unconsciously translates this physical affection into: * loneliness (taking away or exclusion from the usual surroundings of those who are in good health) * "blues" * lack of dynamism * uselessness, feeling of being incompetent "in those conditions, what's the use of fighting?" ٜ At the same time - loss of social status: "Colleagues get up to go to work, children go to school, all the others are productive, I'm good at nothing." - impression of uselessness, dependence; reinforcement of turning in on the self. •The undertaking by a surgeon and his team (anaesthetist, nurse, physiotherapist) which implies constraints, orders, assessments, exercices turns the patient into an "under ling" and makes him lose his independence. Patient's self-concept is modified by the disease and its treatment. Modification of his role in the family and in the society leads him to behave as a man of leisure as an assisted person (3rd age concept).Return to work: If it is desirable, it is not always possible, 3 cases may occur: 1 - occupational activity is incompatible 2 - occupational activity is compatible if the workplace is adapted 3 - occupational activity is compatible. Occupational activity is incompatible. It only involves patients with demanding occupational activities with prolonged upright stance and load carrying or working at a height. Craftsmen and farmers adjust their activity and return to their former work.Associated lesions are often responsable for the absence of return to work. * If the patient had an occupational accident: at the time of finalisation, he will be proposed a permanent partial disablement pension. His rate is determined by the medical consultant. * If the patient is under a sick leave scheme, he can benefit from daily compensation for a maximum of three years. Nonetheless, if his state is stabilized before the end of this period, the medical consultant can set a date of return to occupational activities. If the patient has an employer, he can have a pre-return to work examination by the occupational doctor who will determine a temporary incapacity which may turn into definitive incapacity. The attending physician can then apply for a disablement pension and the medical consultant will be required to determine the level of incapacity exhibited by the patient. For a patient to benefit from a disablement pension, his capacity to work will have to be reduced by two thirds by the disabling affection. Several elements have to be taken into account: - the pathological state itself - the particular elements of the individual considered, these elements can increase or decrease the after-effect of the psychological factors. It involves the general state of health, the age, the physical and mental abilities, and those of vocational training and of the job carried out. - social elements have to be taken into account, what are the actual possibilities for the salaried employee to find a job according to the labour market context of the region he lives in. Occupational activities possible subject to: - workplace adjustment - vocational training. If the patient has no employer, he will be examined by the doctor responsable for the re-employment who will assess with him the characteristics of the workplace wanted.If the patient has an employer, a workplace which physical constraints will be compatible with the handicap of the patient will be searched for in collaboration with the occupational doctor.If no workplace adaptation is possible, vocational training will be considered. It observes relatively strict rules and will only be proposed to the youngest patients. This vocational training session will prolong the work break to a year. This will only be possible with the agreement of the COTOREP (vocational guidance and professional rehabilitation technical commission) and from the patient it needs strong motivation, a certain academic level and a match between the patients' desire, their human qualities and their intellectual abilities is essential. It is a real strategy which is implemented to lead a patient to register at a vocational training centre (there are 100 of them in France).Vocational orientation and problem assessment must be undertaken early enough so that they can repress the psychological inhibitions and take advantage of the functional rehabilitation time to determine the academic level and improve it if necessary. - Motivation: The patient must be personally motivated to undertake a vocational training program which will last for a long time and will keep him far away from his family and his emotional environment. The vocational training program thus cannot be undertaken following the set, the employer or right-thinking people entreaties. Sometimes secondary advantages can favour or oppose a vocational training assessment and this must be taken into account. - Academic level: The level of vocational training will be proportional to the academic level at that time. It will thus be assessed and remedial teaching will be planned early to reinforce academic knowledge which has been acquired but not used so may have been forgotten. A certain number of means will be implemented: - Potentialities: Even if a patient has a low academic level, he may have intellectual faculties of conceptualization of practical turn of mind, of memory which will allow him to rapidly acquire a good level of knowledge. The patients will be offerred information on the subject of carreers, pathways and academic level required. It is advisable that they should be accompanied in this step by competent librarians. Compatible occupational activity: Functional rehabilitation will be completed by retraining aiming at recovering stamina and at intensifying physical activities level essentially by play or sports activities. In some cases, retraining in a specialized centre can be considered. Social and professional difficulties which go together with resettlement of patients with total hip prostheses justify the therapeutic team involvment completed by the presence of the medical consultant, the occupational doctor and social organisations particularly the COTOREP. The medical consultant will be required for the pre-return examination, will determine whether a return to work is possible, the temporary incapacity, the definitive incapacity and will start the presentation before the COTOREP to obtain the recognition of disabled worker and undertake a vocational training program. He is in charge of the worker's follow-up after his return to occupational activities.The medical consultant will decide on the return to occupational activities as soon as the medical state is stabilized and before the 3rd year, the deadline of the work break duration. He may in case of definitive incapacity apply for a fast-track disablement file. He will determine the disability rate for workers under sick leave scheme and will determine the definitive partial disability rate for patients with occupational accidents.


Immunological determination of digestive rates in the syntopic scorpions Urodacus armatus Pocock and Urodacus novaehollandiae Peters.
Scorpions have lengthy periods of inactivity, which may be caused either by a long physiological digestion time or predator avoidance or both. We used a quantitative immunological assay to monitor the amount of prey antigen remaining in the hepatopancreas of Urodacus armatus and U. novaehollandiae for 32 days after a meal to test the hypothesis of a long digestion time. In both species, prey antigen concentration in the hepatopancreas increased between 0.25 and 0.5 days after feeding, probably because of incomplete transfer of prey proteins from the large preoral cavity to the hepatopancreas at this stage of digestion. This was followed by a rapid decline, and by 3 days after feeding less than 25% of ingested antigen remained in each species. Small prey residues could still be detected up to 32 days. Prey decay curves in both species were best fitted by a log-log transformation, and were not significantly different. Since digestion is essentially complete after 3 days, it appears that longer periods of post-feeding inactivity are for predator avoidance, not digestion. However, the 32-day detection period exceeds those reported for other invertebrates, and suggests an unusual digestive physiology in scorptions.


Postprandial hyperlipemia inhibits platelet aggregation without affecting prostanoid metabolism.
The objective of this work was to characterize changes in platelet aggregability during postprandial hypertriglyceridemia with special emphasis on arachidonic acid metabolism. Ten healthy young men consumed 100 g fat after a fasting period of 12 hr. In-vitro platelet aggregation induced by ADP and collagen was measured at 0, 3, 5, and 9 hours after the fat intake. The major arachidonic acid metabolites, 12-hydroxyeicosatetraenoic acid (12-HETE), thromboxane A2 (TXA2), prostaglandin F2 alpha (PGF2a), and prostaglandin E2 (PGE2) produced during collagen-induced platelet activation were quantified by gas chromatography/mass spectrometry. A significant decrease in platelet aggregability induced by both ADP and collagen was detected during the postprandial hyperlipemia. No significant changes could be found in the prostanoid pattern of collagen activated platelets. There was no correlation between the degree of the inhibition of platelet aggregation and the relative or absolute increase of triglyceride-levels in the plasma during the postprandial hyperlipemia.


Gd2O3/b-TiO2 composite nanoprobes with ultra-high photoconversion efficiency for MR image-guided NIR-II photothermal therapy.
Photothermal therapy (PTT), as an important noninvasive and effective tumor treatment method, has been extensively developed into a powerful cancer therapeutic technique. Nevertheless, the low photothermal conversion efficiency and the limited tissue penetration of typical photothermal therapeutic agents in the first near-infrared (NIR-I) region (700-950 nm) are still the major barriers for further clinical application. Here, we proposed an organic/inorganic dual-PTT agent of synergistic property driven by polydopamine-modified black-titanium dioxide (b-TiO2@PDA) with excellent photoconversion efficiency in the second NIR (NIR-II) region (1000-1500 nm). More specifically, the b-TiO2 treated with sodium borohydride produced excessive oxygen vacancies resulting in oxygen vacancy band that narrowed the b-TiO2 band gap, and the small band gap led to NIR-II region wavelength (1064 nm) absorbance. Furthermore, the combination of defect energy level trapping carrier recombination heat generation and conjugate heat generation mechanism, significantly improved the photothermal performance of the PTT agent based on b-TiO2. The photothermal properties characterization indicated that the proposed dual-PTT agent possesses excellent photothermal performance and ultra-high photoconversion efficiency of 64.9% under 1064 nm laser irradiation, which can completely kill esophageal squamous cells. Meanwhile, Gd2O3 nanoparticles, an excellent magnetic resonance imaging (MRI) agent, were introduced into the nanosystem with similar dotted core-shell structure to enable the nanosystem achieve real-time MRI-monitored cancer therapeutic performance. We believe that this integrated nanotherapeutic system can not only solve the application of PTT in the NIR-II region, but also provide certain theoretical guidance for the clinical diagnosis and treatment of esophageal cancer.


The new improved silastic band for ligation of fallopian tubes.
Twelve different sizes of elastic bands were tried in animal experimentation for tubal sterilization. Reversible sterilization was not successful in any of the animals after removal of the various-sized bands. A new elastic Silastic band is reported which is larger and wider than those previously described. Over a 4-year period, no serious complications have been reported and extremely low pregnancy rates have been achieved by utilizing the new, wider bands and our applicators for human sterilization.


Excess cases of prostate cancer and estimated overdiagnosis associated with PSA testing in East Anglia.
This study aimed to estimate the extent of 'overdiagnosis' of prostate cancer attributable to prostate-specific antigen (PSA) testing in the Cambridge area between 1996 and 2002. Overdiagnosis was defined conceptually as detection of prostate cancer through PSA testing that otherwise would not have been diagnosed within the patient's lifetime. Records of PSA tests in Addenbrookes Hospital were linked to prostate cancer registrations by NHS number. Differences in prostate cancer registration rates between those receiving and not receiving prediagnosis PSA tests were calculated. The proportion of men aged 40 years or over with a prediagnosis PSA test increased from 1.4 to 5.2% from 1996 to 2002. The rate of diagnosis of prostate cancer was 45% higher (rate ratios (RR)=1.45, 95% confidence intervals (CI) 1.02-2.07) in men with a history of prediagnosis PSA testing. Assuming average lead times of 5-10 years, 40-98% [corrected] of the PSA-detected cases were estimated to be overdiagnosed. In East Anglia, from 1996 to 2000, a 1.6% excess of cases was associated with PSA testing (around a quarter of the 5.3% excess incidence cases observed in East Anglia from 1996 to 2000). Further quantification of the overdiagnosis will result from continued surveillance and from linkage of incidence to testing in other hospitals.


Improving access to diabetes care for children: An evaluation of the changing diabetes in children project in Kenya and Bangladesh.
The changing diabetes in children (CDiC) project is a public-private partnership implemented by Novo Nordisk, to improve access to diabetes care for children with type 1 diabetes. This paper outlines the findings from an evaluation of CDiC in Bangladesh and Kenya, assessing whether CDiC has achieved its objectives in each of six core program components. The Rapid Assessment Protocol for Insulin Access (RAPIA) framework was used to analyze the path of insulin provision and the healthcare infrastructure in place for diagnosis and treatment of diabetes. The RAPIA facilitates a mixed-methods approach to multiple levels of data collection and systems analysis. Information is collected through questionnaires, in-depth interviews and focus group discussions, site visits, and document reviews, engaging a wide range of stakeholders (N = 127). All transcripts were analyzed thematically. The CDiC scheme provides a stable supply of free insulin to children in implementing facilities in Kenya and Bangladesh, and offers a comprehensive package of pediatric diabetes care. However, some elements of the CDiC program were not functioning as originally intended. Transitions away from donor funding and toward government ownership are a particular concern, as patients may incur additional treatment costs, while services offered may be reduced. Additionally, despite subsidized treatment costs, indirect costs remain a substantial barrier to care. Public-private partnerships such as the CDiC program can improve access to life-saving medicines. However, our analysis found several limitations, including concerns over the sustainability of the project in both countries. Any program reliant on external funding and delivered in a high-turnover staffing environment will be vulnerable to sustainability concerns.


A follow-up survey of family physicians' interest in and knowledge of nutrition.
Forty-two practicing family physicians completed a questionnaire about 33 nutrition topic areas. They were among 71 physicians who, over an eight-year period (1980-1988), completed an identical questionnaire upon entry to their first postgraduate year in the family practice residency program at Brown University/Memorial Hospital of Rhode Island. Specific topic areas were grouped into five scales. Perceived knowledge of these topics significantly increased (p less than .0001) in all areas except nutritional biochemistry. There was significantly less (p less than .0001) interest in learning more about nutrition. One major exception was that the physicians wanted to learn more about nutrition counseling. Another exception was that nutrition in the life cycle remained an area about which they wanted to learn more. The physicians rated nutritional skills as less relevant on the second questionnaire than on the first. The authors conclude that more emphasis on nutrition counseling skills and nutrition in the life cycle may be appropriate in medical education.


Neurovascular injuries of the spinal cord.
Neurovascular spinal cord injuries are very prevalent and in a busy trauma center radiology practice these injuries are commonly seen. Imaging neurovascular injuries has been greatly facilitated by magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). The histopathological changes that occur with spinal cord trauma have been found to correlate well with what is seen on MRI examinations. The MRI findings in spinal cord trauma have also been found to be useful in determining patient prognosis. Spinal cord infarcts due to arterial injury from trauma are relatively rare, but it has been shown by imaging that vertebral artery injuries are not an unusual occurrence. The specific findings associated with neurovascular injuries will be described with an emphasis on the findings on MRI and MRA examinations. MRI and MRA techniques have become the procedure of choice for evaluating neurovascular injuries because of their proven accuracy and because they are non-invasive. Conventional angiography, although, does remain quite useful for evaluating arterial injuries.


Computer simulation assesses PI design prior to implementation.
Hospital seeks sense of assurance that process will work. Consultants apply process capability tools from industry. Nurses' time estimates are compared to historical data.


Bone disease after orthotopic liver transplantation.
After orthotopic liver transplantation (OLT), not infrequently a deterioration of bone disease leading to compression fractures of vertebrae is seen. In a consecutive series of 36 adult OLT patients, we studied, clinically and radiologically, the incidence and degree of bone disease before and after OLT; we also studied whether clinical, radiological and laboratory findings were related to the event of postoperative vertebral collapse. Before OLT, radiological signs of mostly slight osteoporosis were seen in a minority of patients. After OLT, 38% of patients developed vertebral collapse, mainly in the second trimester. Collapse occurred in both previously normal and abnormal vertebrae. Of the preoperative parameters sex, age, menopause, intake of prednisolone, duration and diagnosis of liver disease, duration and degree of cholestasis, bone radiology and urinary calcium, only a low urinary calcium was related to postoperative collapse. Of the postoperative parameters duration of cholestasis, urinary calcium, duration of hospital stay, prednisolone dose and outcome in terms of life and death, none was related to collapse. We conclude that vertebral collapse after OLT occurs frequently and is not easily predicted. Early prevention of bone disease in patients with chronic liver disease before OLT and a low steroid-containing immunosuppressive regimen after OLT are advocated.


Inhibition of the degradation of receptor-bound human choriogonadotropin by leupeptin.
The ability of leupeptin to block the degradation of receptor-bound human choriogonadotropin has been studied. It was found that this compound inhibited hormone degradation and intracellular cathepsin B activity in a parallel fasion, without affecting hormone-stimulated steroidogenesis.


Fossorial adaptations in African mole-rats (Bathyergidae) and the unique appendicular phenotype of naked mole-rats.
Life underground has constrained the evolution of subterranean mammals to maximize digging performance. However, the mechanisms modulating morphological change and development of fossorial adaptations in such taxa are still poorly known. We assessed the morpho-functional diversity and early postnatal development of fossorial adaptations (bone superstructures) in the appendicular system of the African mole-rats (Bathyergidae), a highly specialized subterranean rodent family. Although bathyergids can use claws or incisors for digging, all genera presented highly specialized bone superstructures associated with scratch-digging behavior. Surprisingly, Heterocephalus glaber differed substantially from other bathyergids, and from fossorial mammals by possessing a less specialized humerus, tibia and fibula. Our data suggest strong functional and developmental constraints driving the selection of limb specializations in most bathyergids, but more relaxed pressures acting on the limbs of H. glaber. A combination of historical, developmental and ecological factors in Heterocephalus are hypothesized to have played important roles in shaping its appendicular phenotype.


Anatomical features of skull base and oral cavity: a pilot study to determine the accessibility of the sella by transoral robotic-assisted surgery.
The role of transoral robotic surgery (TORS) in the skull base emerges and represents the natural progression toward miniinvasive resections in confined spaces. The accessibility of the sella via TORS has been recently described on fresh human cadavers. An anatomic study is mandatory to know if this approach would be feasible in the majority of patients regardless of their oral morphological features. From 30 skull base CT scans from patients who were asked to open their mouth as wide as they can, we measured specific dimensions of the oral cavity and the skull base, such as length of the palate, mouth opening and distance from the sella to the palate. All data were acquired on a sagittal midline plane and on a 25° rotation plane, which simulated the axis of the robotic instruments. Looking at the projection of the dental palatine line on the sella, we studied possible predictive factors of sellar accessibility and tried to bring objective data for surgical feasibility. We also proposed an angle α to study the working angle at the skull base. We observed that the maximal mouth opening was a good predictive factor of sellar accessibility by TORS (p < 0.05). The mouth aperture threshold value for a good sensitivity, over 80 %, was comparable to the mean value of mouth opening in our series, 38.9 and 39.4 mm respectively. Moreover, we showed a statistically significant increase of the working angle α at the skull base comparing the lateral access to the midline one (p < 0.05). This seemed to quantitatively demonstrate that the robotic arms placed at the labial commissure of the mouth can reach the sella. From these anatomical features and previous cadaveric dissections, we assume that TORS may be feasible on a majority of patients to remove pituitary adenomas.


Hospitalisations Related to Adverse Drug Reactions in Switzerland in 2012-2019: Characteristics, In-Hospital Mortality, and Spontaneous Reporting Rate.
Adverse drug reactions (ADRs) contribute to morbidity, and serious ADRs may cause hospitalisation and death. This study characterises and quantifies ADR-related hospitalisations and subsequent in-hospital deaths, and estimates the spontaneous reporting rate to regulatory authorities in Switzerland, where healthcare professionals are legally obliged to report ADRs. This retrospective cohort study from 2012 to 2019 analysed nationwide data from the Federal Statistical Office. ICD-10 coding rules identified ADR-related hospitalisations. To estimate the reporting rate, individual case safety reports (ICSRs) collected in the Swiss spontaneous reporting system during the same period were considered. Among 11,240,562 inpatients, 256,550 (2.3%) were admitted for ADRs, 132,320 (51.6%) were female, 120,405 (46.9%) were aged ≥ 65 (median of three comorbidities, interquartile range [IQR] 2-4), and 16,754 (6.5%) were children/teenagers (0 comorbidities, IQR 0-1). Frequent comorbidities were hypertension (89,938 [35.1%]), fluid/electrolyte disorders (54,447 [21.2%]), renal failure (45,866 [17.9%]), cardiac arrhythmias (37,906 [14.8%]), and depression (35,759 [13.9%]). Physicians initiated 113,028 (44.1%) of hospital referrals, and patients/relatives 73,494 (28.6%). Frequently ADR-affected were the digestive system (48,219 [18.8%], e.g. noninfective gastroenteritis and colitis), the genitourinary system (39,727 [15.5%], e.g. acute renal failure), and the mental/behavioural state (39,578 [15.4%], e.g. opioid dependence). In-hospital mortality was 2.2% (5669). Since ICSRs indicated 14,109 hospitalisations and 700 in-hospital deaths, estimated reporting rates were 5% and 12%, respectively. This 8-year observation in Switzerland revealed that 2.3%, or roughly 32,000 admissions per year, were caused by ADRs. The majority of ADR-related admissions were not reported to the regulatory authorities, despite legal obligations.


Risk-Based Therapeutic Strategies for HER2-Positive Early Breast Cancer: A Consensus Paper.
Breast cancer represents the most commonly diagnosed neoplasm worldwide and the HER2-positive subtype accounts for nearly 1 in 5 breast cancers. The majority of patients with breast cancer present with an early-stage disease upon diagnosis, which is thus susceptible to virtually curative treatment strategies. For a stage, I T1a/b N0 HER2-positive disease, upfront surgery followed by adjuvant therapy is the preferred approach. However, there is some uncertainty regarding the appropriate management of stage cT1c cN0, as both the neoadjuvant approach and upfront surgery have been proven to be feasible therapeutic options. The aim of this Delphi consensus was to define the best strategies for the treatment of early HER2-positive breast cancer. This work may help clinicians in the management of early HER2-positive breast cancer.


Anaesthesia and glucose-6-phosphate dehydrogenase deficiency. A case report and review of the literature.
Anaesthetic management of a patient with glucose-6-phosphate dehydrogenase deficiency is described. The pathogenesis and various complications relating to this common hereditary blood disorder are reviewed. Problems related to anaesthesia in the presence of glucose-6-phosphate dehydrogenase deficiency are discussed.