Release of sarcoplasmic enzymes from skeletal muscle by Bothrops jararacussu venom: antagonism by heparin and by the serum of South American marsupials.
The venom of B. jararacussu induced a time- and dose-dependent (2-100 micrograms/ml) increase in the rate of release of sarcoplasmic enzymes (CK and LDH) from isolated rat and frog muscles. This effect, which we attribute to sarcolemmal damage by the venom, persisted in a Ca2+-free media, suggesting that phospholipase A activity was not required. The venom-induced enzyme release from the isolated muscles was reversibly inhibited by the sera (1-10 microliters/ml) of the marsupials Didelphis marsupialis aurita and Philander opossum, by an acidic glycoprotein fraction isolated from the opossum serum (50 micrograms/ml), and by heparin (50 micrograms/ml). Incubation of the B. jararacussu venom with opossum sera or heparin prevented the increase in plasma CK level observed in mice in which the snake venom (2.5-5.0 micrograms/g) was injected i.m. It is suggested that formation of acid-base complexes between basic myotoxins of B. jararacussu venom and either acidic components in the marsupial sera or the polyanionic heparin could account for the inhibition of the in vitro and in vivo effects of the venom on the release of sarcoplasmic enzymes from skeletal muscles.


Effects of X-ray irradiation on the fitness of the established invasive pest fall armyworm Spodoptera frugiperda.
Spodoptera frugiperda has spread to Africa, Asia, and Oceania, posing a serious threat to global agriculture. We estimated the appropriate dose of X-ray sterilization for S. frugiperda using an X-ray irradiation instrument to investigate environmentally acceptable control techniques, laying the framework for future applications of sterile insect technology (SIT) to manage the pest environmentally-friendly. This study is the first to investigate the effects of X-ray irradiation on the growth, development, survival, reproduction, and flight of S. frugiperda. The results showed that irradiation with 50-400 Gy had no significant effect on pupal eclosion, but females were more sensitive than males in terms of reproductive parameters, especially when doses of radiation were > 350 Gy. After irradiation with a sub-sterilizing dose of 250 Gy, the parental sterility rate was > 85%, and the sterility traits could be passed on to their offspring, resulting in a continuous decrease in the population of F1 and F2 generations. Our laboratory experiments theoretically confirmed the feasibility of SIT for controlling S. frugiperda in the field using X-ray radiation. This study provides a theoretical basis for future regional pest management strategies. © 2022 Society of Chemical Industry.


Structural investigation of aroylhydrazones in dimethylsulphoxide/water mixtures.
Molecular structures of aroylhydrazones derived from salicylaldehyde, o-vanilin and nicotinic acid hydrazide in DMSO and DMSO/H(2)O mixtures have been studied by NMR, UV-Vis, ATR and Raman spectroscopy. The addition of water to the system did not induce the tautomeric conversion of the existing form constituted of the ketoamino hydrazide part and the enolimino aldehyde part, but it was involved in the formation of hydrated molecules. Vibrational spectra (ATR and Raman) clearly indicated hydrogen bonding of the studied hydrazones through the carbonyl, amino and hydroxyl groups with water molecules. Increasing the water content conversion from E to Z isomer was not observed.


Acute spinal epidural empyema. Observations from seven cases.
Seven cases with an acute epidural spinal empyema are presented. The best results are observed in cases with early treatment. Since this rare condition is not widely known and swift diagnosis and treatment is imperative, it is stressed that immediate referral of the patient with back pain and any signs of infection in addition to commencing neurological abnormalities to a neurological unit for myelography can be vital or can at least reduce the risk of permanent paraplegia.


Evidence related to the use of ancillary drugs in bovine respiratory disease (anti-inflammatory and others): are they justified or not?
The therapeutic approach for bovine respiratory disease (BRD) includes antimicrobial treatment due to the frequent implication of bacteria. The data concerning the use of ancillary drugs (such as anti-inflammatory drugs or immunomodulators) are scant and often are based on experimental models of BRD. The effect of NSAIDs on pulmonary lesions, despite appearing beneficial, remains to be confirmed in well-designed, long-term trials. The impact on weight gain is inconsistent in these studies. This review emphasized the need for articles concerning clinical trials to clearly state study inclusion criteria, and definitions of clinical scores, relapses, and treatment failures to be properly evaluated.


[Clinical evaluation of Dumon stent for tracheobronchial stenosis due to advanced esophageal carcinoma].
We inserted Dumon stent to 13 patients with tracheobronchial stenosis due to advanced or recurrent esophageal carcinoma. Severe dyspnea was improved in 11 patients except for 2 patients with bilateral recurrent nerve palsy. 3 cases who had radiation therapy or chemotherapy lived over 150 days. We inserted esophageal stent in 4 cases. 2 patients died due to hemoptysis after 156 days and 35 days. We conclude that Dumon stent is one of the useful treatments in order to improve quality of life and prognosis of advanced or recurrent esophageal carcinoma.


Elevated serum cathepsin B concentration in pregnant women is associated with preeclampsia.
To compare the circulating levels of cathepsins B and D in preeclamptic and normotensive pregnancies. Seventy-two pregnant patients were enrolled in this study. Of the 72 pregnant patients, 25 were preeclamptic and 47 patients were normotensive. Serum levels of soluble cathepsins B and D were measured with an enzyme-linked immunosorbent assay (ELISA) kit. Cathepsin B levels were significantly higher in preeclamptic women than normotensive pregnant women (125.9 vs. 41.9 ng/mL; p = 0.013). The serum levels of cathepsin D were lower in preeclamptic women, but the differences were not significant (129.3 vs. 200.9 ng/mL; p = 0.077). However, cathepsin B and D levels were not correlated with severity of preeclampsia and small for gestational age. The serum levels of cathepsin D were inversely correlated with uric acid in preeclamptic patients (r = -0.527; p = 0.03). The serum levels of cathepsin B levels were increased significantly in preeclamptic women. Correlation with severity of preeclampsia needs further investigation to clarify the role of cathepsin B.


Apoplast-symplast compartmentalization and functional traits of iron and aluminum in promeristematic tissues of nematode induced galls on Miconia spp.
The nutritive tissues of galls induced by Ditylenchus gallaeformans (Nematoda) have promeristematic capacity, which may turn these galls into sinks of Al on their Melastomataceae Al-accumulating hosts. Such a sink of Al may affect gall growth and mineral nutrient intake. Based on the fact that galls are good models for plant developmental studies, we aimed to understand how Al-accumulating host plants in the Cerrado environment deal with Al toxicity in subcellular levels. Here, we used the ICP-OES method to check the variations on mineral nutrients, and the morin, hematoxylin, and Prussian blue stainings for Al and Fe histolocalization in galls induced on four Miconia species of the Brazilian Cerrado. We confirmed the new Al-accumulating feature for two Miconia species of the Cerrado environment. Furthermore, we found that Al accumulates in lesser concentrations in gall tissues than in non-galled tissues of the Miconia hosts. Staining methods indicated that the polyphenols avoid Al-binding to the apoplast and the nucleolus of the promeristematic cells, and mediated its binding to parenchyma cell walls. As well, we inferred that Fe3+ is transported by xylem and stored in gall parenchyma, where it is reduced to Fe2+, being available in gall nutritive cells. Our results demonstrated an Al compartmentalization between the apoplast and symplast of the inner cell layers in galls, as well as indicated the phenolics action against Al-toxicity and toward Fe availability for the diet of Ditylenchus gallaeformans.


[Pyonephrosis: 44 cases in Senegal].
To report epidemiological, clinical and paraclinical features of pyonephrosis and describe current management methods in Senegal. This retrospective study includes a series of patients admitted for pyonephrosis to the Urology Department of the Aristide Le Dantec Hospital in Dakar between 1995 and 2009. The following information was collected for each patient: age, sex, clinical manifestations, diagnostic findings, treatment modalities and outcomes. A total of 44 patients with a mean age of 34 years were included. The most common clinical manifestations were acute flank pain, sepsis and renal mass. Diagnostic was usually based on medical imaging, i.e., renal utrasonography and computed tomography. Urolithiasis was the underlying etiology in 73.2% of cases. Nephrectomy was performed in 83% of cases with or without preliminary nephrostomy catheterization. Development of both diagnostic (medical imaging) and therapeutic methods for management of pyonephrosis has been consistent with the rarity of this condtion in Senegal.


Correlation between Serum SCCA and CYFRA 2 1-1, Tissue Ki-67, and Clinicopathological Factors in Patients with Esophageal Squamous Cell Carcinoma.
Squamous cell carcinoma antigen (SCCA) and CYFRA 21-1 have been reported as useful tumor markers for esophageal squamous cell carcinoma (ESCC), but no information has yet been reported about the relationship between these serum tumor markers and tissue proliferative activity (Ki-67) in ESCC patients. To study the correlation between SCCA, CYFRA 21-1, Ki-67, and clinicopathological factors in ESCC patients. Pretreatment SCCA and CYFRA 21-1 serum levels were measured, while the expression of Ki-67 was assessed on tumor tissue. The associations between these biomarkers, clinicopathological factors, and overall survival were analyzed. One hundred sixty six patients participated in this study. Elevated SCCA and CYFRA 21-1 were found in 78.9% and 50.0% of the patients, respectively, while 42.8% had both serum markers elevated. The SCCA and CYFRA 21-1 levels were not correlated (p = 0.128) to each other nor to age, sex, T N, M location, grade, or Ki-67. High Ki-67 expression levels were significantly correlated with T4 (p = 0.010), M1 (p = 0.010), and poor grade (p = 0.015) but not to age, sex, N, or location. Levels of SCCA, CYFRA 21-1, and Ki-67, alone or in any combination, were not correlated to survival of patients. The authors showed that Ki-67 in tumor tissue is probably a more reliable marker than serum SCCA and CYFRA 21-1 in predicting the clinical course of ESCC.


Studies with GMP synthetase from Ehrlich ascites cells. Purification, properties, and interactions with nucleotide analogs.
GMP synthetase has been purified 57-fold from Ehrlich ascites cells. The enzyme was found to be stable and to have an approximate molecular weight of 85,000 (determined by gel filtration). Its activity was stimulated by dithiothreitol and inhibited by 2-mercaptoethanol, p-chloromercuribenzoate, and hydroxylamine. Both ammonia and glutamine could serve as amino group donors. While none of the 10 triphosphate purine and pyrimidine nucleotides studied were able to substitute for ATP as the energy donor for the reaction, all of these compounds were able to bind to the ATP site. The Ki values for CTP, beta-D-arabinofuranosyl-ATP, and 1-N6-ethenoATP were slightly lower than the Km of ATP (0.28 mM). Six monophosphate nucleotides were aminated by this enzyme. Listed in order of their substrate efficiency (Vmax/Km), they are: xanthosine 5'-phosphate(XMP) (28,000); 2'-dXMP (1,200); 8-azaXMP (320); 6-thioXMP (200); beta-D-arabinofuranosyl-XMP (72); 1-ribosyloxipurinol 5'-phosphate (0.5). 6-ThioXMP was a strong alternative substrate inhibitor with a Ki of 5 muM. The aminated products of the reaction (four studied) were competitive inhibitors with respect to XMP.


Implementing non-invasive prenatal testing into publicly funded antenatal screening services for Down syndrome and other conditions in Aotearoa New Zealand.
Non-invasive prenatal testing (NIPT) is a relatively new screen for congenital conditions - specifically, common fetal aneuploidies including Down Syndrome. The test is based on isolating freely circulating fragments of fetal-placental DNA that is present in the mother's blood. NIPT has a superior clinical performance compared to current screening, and has been available privately in Aotearoa New Zealand for the last 4 years. The proposed implementation of NIPT as a publicly funded service may widen the inequity in access to optional antenatal screening that already exists in this country. This paper discusses precautions that can be taken at the health system, organisation, and personnel levels to ensure that access to NIPT is equitable, that services are culturally responsive, and women's informed choice is promoted and protected. The adoption of NIPT into publicly funded services is an example of how genetic screening is becoming mainstreamed into health services; as such our approach may also have relevance around the introduction of other genetic and genomic screening initiatives.


Effect of Signal Intensity on Measurement of Ganglion Cell Complex and Retinal Nerve Fiber Layer Scans in Fourier-Domain Optical Coherence Tomography.
We determined the effect of Fourier-domain optical coherence tomography (OCT) signal strength index (SSI) and cropping on retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC) scan repeatability and measurement thickness. Eyes were enrolled in the longitudinal Advanced Imaging for Glaucoma Study. At each visit, three repeat scans from the optic nerve head and macular protocols were obtained. Each measurement was associated with an SSI value from 0 to 100. Measurements with similar SSI scores were grouped to calculate repeatability defined as pooled standard deviation. Within-visit analysis was used to determine how measured thickness changed in relation to change in SSI level. The study included 1130 eyes of 569 patients. Cropped images yielded significantly worse repeatability and they were excluded from subsequent analyses. The within-visit repeatability for RNFL and GCC measurements were significantly better with higher signal strength, and optimal cutoffs were SSI ≥ 37 and ≥ 44, respectively. The coefficient of variation was <1.8% for RNFL scans with SSI ≥ 37 and < 2% for GCC with SSI ≥ 44. For scans above the cutoff SSI, higher SSI's were correlated with thicker RNFL among normal (slope = 0.056 μm/SSI unit, P < 0.001) eyes and glaucoma suspect and perimetric glaucoma (GSPPG) eyes (slope = 0.060 μm/SSI unit, P < 0.001), but not for perimetric glaucoma (PG) eyes. No significant correlation was found for GCC. Repeatability of RNFL and GCC thickness measurements may be improved by excluding images with cropped anatomic features and weak signal strength below recommended SSI cutoffs. Measurement precision and image quality of inner eye structure by advanced imaging modality are important for clinical diagnosis and tracking of glaucoma disease.


Formation mechanism of nanotubes comprising layers of PbS nanoparticles in polymer-surfactant solutions.
The crystallization of PbS in aqueous solutions containing the surfactant sodium dodecyl sulfate (SDS) and hydrophilic polymers resulted in a novel type of metastable nanotubes, the walls of which consist of layers of ordered PbS nanoparticles, apparently separated by layers of surfactant molecules. Information on the mechanism of formation of these structures was obtained by focusing on the roles of the polymer, and of the insoluble lead dodecyl sulfate (Pb(DS)2) present in the system. TEM investigations of the early stages of crystallization revealed the coexistence of PbS and Pb(DS)2 precipitates, the latter being surprisingly important for nanotube formation, and allowed to follow the evolution of layered structures from combination of the two types of crystals. Six different hydrophilic polymers have been used, which interact with SDS with varying strengths. Surprisingly, and in contrast to previous hypotheses, layered nanostructures were observed in all polymer solutions, regardless of the strength of polymer-surfactant interactions. This indicates that, although the presence of a polymer is necessary, polymer-SDS interactions are not a driving force for the formation of the layered structures and nanotubes. On the contrary, the interactions between the polymer chains and the growing particles appear to be of the utmost importance. Results presented here can be interpreted in terms of two alternative mechanisms for layered nanostructure and nanotube formation.


Histone acetylation plays an important role in MC-LR-induced apoptosis and cycle disorder in SD rat testicular cells.
Microcystin-leucine arginine (MC-LR) is a variant of microcystins (MCs), which poses a serious threat to the reproductive system. Histone acetylation modification can regulate the expressions of apoptosis-related genes. However the mechanisms of histone acetylation involving MC-LR-induced apoptosis were not understood. This study investigated the change of histone acetylation and its role in apoptosis and cell cycle arrest induced by MC-LR. MC-LR enhanced the activity of histone deacetylase (HDAC), decreased the activity of histone acetylase (HAT), up-regulated the expression of HDAC1, and down-regulated the expressions of Ac-H3 and Ac-H4 in vitro and vivo. Meanwhile, MC-LR induced testicular tissue injury and increased the expressions of apoptosis-related genes, such as Bax, Caspase3 and Caspase8, ultimately causing cells apoptosis in testicular tissues. Furthermore, MC-LR also induced cell cycle arrest in S phase, increased the expression of P21Wif1/Cip1, and inhibited the expressions of cyclinD1, cyclinE1, CDK2 and E2F1. Importantly, HDAC inhibitor Trichostatin A (TSA) could ameliorate MC-LR-induced apoptosis and cell cycle arrest by reverse-regulating the expressions of these proteins. These results indicated that MC-LR could activate the mitochondrial apoptotic pathway and disorder the cell cycle pathway to induce the cell apoptosis by enhancing HDAC activity and reducing histone acetylation of normal testicular cells in SD rats. Hence, histone acetylation has a vital function in MC-LR-induced apoptosis in SD rat testicular cells, which provides a new insight on the reproductive toxicity of male induced by MC-LR.


External fixation of the pelvic ring: an experimental study on the role of pin diameter, pin position, and parasymphyseal fixator pins.
The mechanical properties of current external fixator systems for unstable (type C) pelvic ring fractures are inferior to internal fixation, and are not optimal for definitive treatment. We explored methods to increase stability of external fixator constructs. An experimental model was used for load tests. The same pelvic fixator was used while different pin diameters, pin positions, and modes of pubic symphysis fixation were tested. Changing of the pin diameter of the unthreaded part from 6 to 8 mm resulted in an increase in stiffness of 20%. An increase in stiffness by a factor of 1.9 was found by placing a pin on the iliac crest and one supra-acetabular. An additional increase by a factor of 3.6 was obtained by adding pubic symphysis plate fixation. Parasymphyseal pin fixation instead reduced stiffness, but not so much as when parasymphyseal pins were connected to the external fixator of the pelvic ring. The final configuration was at least 6 times stiffer than the initial configuration. The new concept of parasymphyseal pin fixation connected to an external fixator of the pelvic ring produces a considerable increase in stability for the treatment of type C pelvic ring injuries, as does an increase in pin diameter and alternative pin positioning.


Connective tissue in diabetes mellitus: biochemical alterations of the intercellular matrix with special reference to proteoglycans, collagens and basement membranes.
Diabetes mellitus induces alterations in the metabolism of the macromolecules present in the intercellular matrices and particularly in the basement membranes. These contribute to the morphological changes characteristic of the disease : basement membrane thickening, skin thickening and induration. Accumulation of overglycosylated collagens and diminution of sulfated proteoglycan concentrations are the most generally reported biochemical modifications in human or animal diabetic states. More limited data are available concerning elastin, fibronectin and laminin in diabetes.


Hot dense capsule-implosion cores produced by Z-pinch dynamic Hohlraum radiation.
Hot dense capsule implosions driven by Z-pinch x rays have been measured using a approximately 220 eV dynamic Hohlraum to implode 1.7-2.1 mm diameter gas-filled CH capsules. The capsules absorbed up to approximately 20 kJ of x rays. Argon tracer atom spectra were used to measure the T(e) approximately 1 keV electron temperature and the n(e) approximately 1-4 x 10(23) cm(-3) electron density. Spectra from multiple directions provide core symmetry estimates. Computer simulations agree well with the peak emission values of T(e), n(e), and symmetry, indicating reasonable understanding of the Hohlraum and implosion physics.


TF/FVIIa/PAR2 promotes cell proliferation and migration via PKCα and ERK-dependent c-Jun/AP-1 pathway in colon cancer cell line SW620.
Our previous study has demonstrated that tissue factor-factor VIIa (TF/FVIIa) complex promotes the proliferation and migration of colon cancer cell line SW620 through the activation of protease-activated receptor 2 (PAR2). In the current study, the underlying molecular mechanisms of TF/FVIIa/PAR2 signaling in SW620 cells were further explored, with the focus on the role of activator protein-1 (AP-1) subunit c-Jun. The results revealed that PAR2-AP and FVIIa could upregulate c-Jun expression and c-Jun phosphorylation in SW620 cells in a time-dependent manner. The effect of FVIIa was significantly blocked by anti-TF and anti-PAR2 antibodies. Protein kinase Cα (PKCα) inhibitor safingol and extracellular signal-regulated kinase 1 and 2 (ERK1/2) inhibitor U0126 abrogated the activation of c-Jun. In contrast, Ca(2+) chelators EGTA and thapsigargin, and p38MAPK inhibitor SB203580 had no effect. Suppression of c-Jun/AP-1 activation using a natural inhibitor curcumin decreased the expression of caspase-3, MMP-9, and TF, as well as the proliferation and migration of SW620 cells induced by PAR2-AP or FVIIa. Collectively, our findings suggest that c-Jun/AP-1 activation is required for TF/FVIIa/PAR2-induced SW620 cell proliferation and migration. PKCα and ERK1/2 are located upstream of c-Jun/AP-1 in this signaling pathway. Pharmacological inhibition of this pathway might be a novel strategy for colon cancer therapy.


From the lab to the prescription pad: genetics, CYP450 analysis, and medication response.
Conventional child and adolescent psychopharmacology practices and its inherent risks are reviewed and the implications of pharmacogenomics and cytochrome P450 (CYP450) analysis are discussed. A case study is utilized to further depict the value of CYP450 analysis. An understanding of pharmacogenomics, specifically the CYP450 enzyme system and its involvement in the metabolism of psychotropic medications, can be utilized to improve child and adolescent psychopharmacology practices by prescribers. An integrative literature review from nursing, psychiatry, medicine, and pharmacology. The current trial and error process of choosing medications for child and adolescent psychiatric patients, and the growing trend of polypharmacy, results in poor outcomes and high risk of serious adverse drug reactions. The utilization of knowledge from the field of pharmacogenomics can improve prescribing practices in child and adolescent psychopharmacology management. Psychiatric nurse prescribers can improve treatment outcomes and reduce adverse drug reactions by incorporating information from the study of pharmacogenomics.


Enhancement of sickle erythrocyte adherence to endothelium by autologous platelets.
The increased adhesiveness of sickle erythrocytes (SS RBC) to endothelial cells has been confirmed in a static system utilizing fresh umbilical vein endothelium. Adherence of SS RBC to the endothelium was as great in the presence of calcium-containing buffer as when incubated in plasma. SS RBC suspended in autologous platelet-rich plasma adhered to a greater extent than when suspended in autologous platelet poor plasma. Prostacyclin, thromboxane B2, and an inhibitor of collagen- and epinephrine-induced platelet aggregation (B13.177) did not affect SS RBC adherence to endothelium. Aspirin in a concentration of 5 micrograms/ml slightly decreased SS RBC adherence to endothelium in the presence of platelets. Platelets may play a significant role in the increased adhesiveness of SS RBC to endothelium. To the extent that increased SS RBC adhesiveness contributes to the genesis of painful crises and to the extent platelets augment this adhesiveness, agents affecting platelet function may prove useful in preventing painful crises.


Cystic schwannoma of the trochlear nerve mimicking a brain-stem tumor. Case report.
A case is reported of a rare cystic schwannoma of the fourth cranial nerve which was interpreted as a probable intrinsic brain-stem lesion. The clinical approach to brain-stem tumors in terms of empirical treatment or surgical biopsy is discussed.


Identification and evaluation of the contribution of the chemoreflex in the hemodynamic response to intracarotid administration of contrast materials in the conscious dog: comparison with the response to nicotine.
Intracarotid administration of ionic contrast material and nicotine in conscious, unsedated dogs caused similar biphasic reflex responses consisting of initial decreases followed by increases in heart rate and pressures. Both phases were characterized by increases in respiratory amplitude. The initial hypotension was not observed when heart rate was maintained constant. The initial bradycardia was absent after denervation of the carotid body and cholinergic blockade. The tachycardia was attenuated after ligation of the internal carotid artery and beta adrenergic blockade. Hwever, the hypertension persisted after denervation of the carotid body and ligation of the internal carotid artery but was attenuated after alpha adrenergic blockade. Nonionic contrast material caused almost no reflex hemodynamic effects. Like noxious substances such as nicotine, ionic contrast materials cause complex hemodynamic effects as a consequence of actions on the cardiovascular centers of the brain, carotid body chemoreceptors, and chemosensitive tissue in the external carotid circulation.


Failure of a branched chain amino acid-enriched diet to reverse ethanol inhibition of cardiac protein synthesis in the rat.
The fractional rate of protein synthesis was determined in the hearts of rats in vivo fed on diets containing 27% of energy as ethanol or on this diet supplemented with 5% of equimolar amounts of branched chain amino acids (BCAA). Administration of ethanol significantly decreased the fractional synthetic rate of mixed cardiac proteins and this depression was not ameliorated by concomitant feeding of BCAA. These data are discussed in relation to the stimulation of cardiac protein synthesis by BCAA observed in vitro.


ZTE MR-based attenuation correction in brain FDG-PET/MR: performance in patients with cognitive impairment.
One of the main challenges of integrated PET/MR is to achieve an accurate PET attenuation correction (AC), especially in brain acquisition. Here, we evaluated an AC method based on zero echo time (ZTE) MRI, comparing it with the single-atlas AC method and CT-based AC, set as reference. Fifty patients (70 ± 11 years old, 28 men) underwent FDG-PET/MR examination (SIGNA PET/MR 3.0 T, GE Healthcare) as part of the investigation of suspected dementia. They all had brain computed tomography (CT), 2-point LAVA-flex MRI (for atlas-based AC), and ZTE-MRI. Two AC methods were compared with CT-based AC (CTAC): one based on a single atlas, one based on ZTE segmentation. Impact on brain metabolism was evaluated using voxel and volumes of interest-based analyses. The impact of AC was also evaluated through comparisons between two subgroups of patients extracted from the whole population: 15 patients with mild cognitive impairment and normal metabolic pattern, and 22 others with metabolic pattern suggestive of Alzheimer disease, using SPM12 software. ZTE-AC yielded a lower bias (3.6 ± 3.2%) than the atlas method (4.5 ± 6.1%) and lowest interindividual (4.6% versus 6.8%) and inter-regional (1.4% versus 2.6%) variabilities. Atlas-AC resulted in metabolism overestimation in cortical regions near the vertex and cerebellum underestimation. ZTE-AC yielded a moderate metabolic underestimation mainly in the occipital cortex and cerebellum. Voxel-wise comparison between the two subgroups of patients showed that significant difference clusters had a slightly smaller size but similar locations with PET images corrected with ZTE-AC compared with those corrected with CT, whereas atlas-AC images showed a notable reduction of significant voxels. ZTE-AC performed better than atlas-AC in detecting pathologic areas in suspected neurodegenerative dementia. • The ZTE-based AC improved the accuracy of the metabolism quantification in PET compared with the atlas-AC method. • The overall uptake bias was 21% lower when using ZTE-based AC compared with the atlas-AC method. • ZTE-AC performed better than atlas-AC in detecting pathologic areas in suspected neurodegenerative dementia.


[Kidney failure during acute pancreatitis. A unique aspect of multiple organ failure].
Eighty-two patients with acute pancreatis observed in the last seven years were included in prospective trial of monitoring protocol comprising: multiple organ failure and non invasive imaging of pancreatic lesion. One organ failure noted in the 60.9%, M.O.F. with three organ failure represented in the 21.9%. Renal failure was confirmed in 18.9%, trough nine clinical and biological index, become with shock in 73% and with extensive necrosis in 53%. ARF appeared with functional picture and normal diuresis in 73.3% and with organic failure in 26.7%. Index of specific mortality was 33.3%, while the comprehensive index of mortality in the study group was 12.9%, with a significant incidence in the half of deaths.


Prevalence and related factors of do-not-resuscitate orders among in-hospital cardiac arrest patients.
Studies concerning do-not-resuscitate (DNR) orders in mainland China are rather scarce. We explored the prevalence and related factors of DNR orders among in-hospital cardiac arrest (IHCA) patients at a general tertiary hospital in mainland China. We identified all IHCA patients hospital-wide between July 2019 and September 2020. Data regarding DNR status were collected from medical records. We investigated the frequency of DNR orders and explored the determinant factors of DNR establishment using logistic regression. A total of 1154 IHCA patients were included, 535 (46.4%) of whom established DNR orders. The following variables were independently associated with a higher DNR rate: female (OR 1.491; 95% CI 1.130-1.965), older age (OR 1.016; 95% CI 1.008-1.024), being a local resident (OR 1.790; 95% CI 1.344-2.383), pulmonary infection (OR 1.398; 95% CI 1052-1.859), respiratory insufficiency (OR 1.356; 95% CI 1.009-1.823), shock (OR 1.735; 95% CI 1.301-2.313), acute stroke (OR 1.821; 95% CI 1.235-2.686),neurological dysfunction (OR 1.527; 95% CI 1.149-2.028) and cancer (OR 3.316; 95% CI 2.461-4.468). Counterintuitively, patients with new-onset coronary artery disease (OR 0.592; 95% CI 0.419-0.837) were less likely to create DNR orders. In mainland China, the DNR order signing rate is low, and the establishment of a DNR order is associated with demographics and comorbidity characteristics.


Hepatic Sinusoidal-obstruction Syndrome and Busulfan-induced Lung Injury in a Post-autologous Stem Cell Transplant Recipient.
Veno-occlusive disease of the liver is mostly encountered as a complication of hematopoietic stem cell transplantation with myeloablative regimens with an incidence estimated to be 13.7%. It is clinically characterized by tender hepatomegaly, jaundice, weight gain and ascites. Strong clinical suspicion and an early recognition of clinical signs are essential to establish the diagnosis and institute effective regimen. Another complication of cytotoxic drugs given for cancers, is development of busulfan-induced lung injury. A strong index of suspicion is needed for its diagnosis, especially in setting where opportunistic fungal and viral infections manifest similarly. We illustrate the clinical and autopsy finings in a 2½-year-old boy who received autologous stem-cell transplantation following resection of stage IV neuroblastoma. He subsequently developed both hepatic veno-occlusive disease and busulfan-induced lung injury. The autopsy findings are remarkable for their rarity.


Co-infections in critically ill adults with severe acute respiratory syndrome coronavirus 2 infection: an Italian multi-center prospective study.
To date, few studies have described Hospital-acquired infections (HAIs) during COVID-19 outbreak. To examine the incidence of HAIs in critically ill adult patients with SARS-CoV-2 infection and to observe risk factors, and the impact on outcome of HAI. A prospective multicenter study was conducted that included adult patients with SARS-CoV-2 infection admitted to 18 Italian Intensive Care Units from September 2020 to November 2021. A total of 589 patients were included. A total of 233 patients were diagnosed with at least one HAI (39.6%). The co-infection/co-colonization rate >48 hours after admission was 31.0 per 1000 person-days (95% CI 18.8-34.8). Age, length of ICU stay >7 days, obesity, type 2 diabetes mellitus, cardiovascular disease, inserted central venous catheter, intubation, APACHE II score >25, mechanical ventilation (MV) >48 hours, obesity and inserted urinary catheter are associated outcomes for infection acquisition. The overall mortality rate of patients was found to be significantly higher in patients who had acquired a HAI (RR=4.37; 95% CI 3.30-5.78; P<0.001). Associated factors for HAI acquisition and mortality in ICU patients were identified and cause for revision of existing infection control policies.


Neourethral meatus reconstruction for vulvectomies requiring resection of the distal part of the urethra.
Vulvar cancer is a relatively rare tumour accounting for just 5% of all gynaecological malignancies. Radical excision can sometimes involve the distal one-third to one-half of the urethra leading to postoperative problems with micturition, asymmetries and psychosexual distress. Although this topic has been largely addressed, no specific method for distal urethra reconstruction has been described. The aim of this paper is to assess the safety and reliability of our reconstructive technique. We conducted a retrospective study of 47 consecutive patients who underwent neourethral meatus reconstruction with vaginal mucosa flap. The surgical technique is described step-by-step. We reviewed the patients' demographics, operative characteristics, as well as immediate complications and long-term outcomes. Neo-meatal reconstruction was combined to direct vulvar closure in 2 patients, rhomboid flaps in 3 cases, 1 bilateral lotus flap and 36 V-Y fasciocutaneous flaps, 4 rectus abdominis and 1 gracilis flap. Wound dehiscence at the site of the neourethral reconstruction occurred in only 4.3%, partial necrosis of the vaginal mucosa flap in 2.1%. Totally post-operative early complication rate including the whole procedures was 29.8% with a re-operation rate of 4.3%. Long-term outcomes were evaluated in 68.1% patients, including 18.7% of urinary incontinence, no urethral stenosis and 25% of narrowed vaginal introitus. Neourethral meatus reconstruction using the vaginal mucosa flap is a simple, safe and reliable technique with a very low early complication rate. We suggest that this flap could be a good option to preserve and restore urinary function in case of distal urethral amputation.


An intracranial/extracranial approach for the surgical management of haemangiomas of the orbit and eyelid.
The authors propose a combined approach for the treatment of orbito-palpebral haemangiomas. Two cases are presented and discussed. Pre-operative evaluation included coronal, axial, and sagittal CT scans as well as a selective arteriogram. These studies assisted the planning of the surgical approach. An intracranial/extracranial surgical approach was used with ocular-palpebral dissection. Pre-operative arterial embolization was helpful in controlling perioperative blood loss. Precise excision of the masses was thus accomplished and functional and aesthetic reconstruction aided by the conservation of normal anatomical structures.


Synthesis of epothilone analogues by antibody-catalyzed resolution of thiazole aldol synthons on a multigram scale. Biological consequences of C-13 alkylation of epothilones.
Three monoclonal aldolase antibodies (84G3, 85H6, and 93F3), generated against a beta-diketone hapten (II) by the reactive immunization technique, catalyzed highly enantioselective retro-aldol reactions of the racemic thiazole aldols 13-20. Antibody 84G3 (0.0004-0.005 mol%) was used to resolve (+/-)-13-(+/-)-18 to afford compounds 13-18 in multigram quantities. Multiple 13-alkyl analogues of epothilone (7-12) and their trans isomers ((E)-7-(E)-12) were synthesized starting from thiazole aldols 13-18. Construction of the trisubstituted olefin moiety in compounds 7-12 and (E)-7-(E)-12 was catalyzed by Grubbs' catalyst (X). Initial biological testing with compounds 7-10 and their trans isomers showed that compounds 9, 10, and (E)-10 have appreciable tubulin polymerization and antiproliferative activities that approached those of epothilone C. The most active compound, (E)-9, even displayed potencies comparable to those observed for epothilones A and D. Interestingly, all trans analogues were more potent than their corresponding cis isomers. While introduction of an alkyl group at C-13 in the cis series led to an overall reduction in biological activity (compared to epothilone C), appropriate modification of the thiazole moiety (replacement of the 2-methyl substituent by a 2-methylthio group) was able to compensate for this loss. These results are encouraging in view of the expectation that epoxidations of these compounds should further increase their cellular activities. Thus, compounds 9, 10, and (E)-9 and (E)-10 represent highly promising candidates for further studies.


Age-dependent structural reorganization of utricular ribbon synapses.
In mammals, spatial orientation is synaptically-encoded by sensory hair cells of the vestibular labyrinth. Vestibular hair cells (VHCs) harbor synaptic ribbons at their presynaptic active zones (AZs), which play a critical role in molecular scaffolding and facilitate synaptic release and vesicular replenishment. With advancing age, the prevalence of vestibular deficits increases; yet, the underlying mechanisms are not well understood and the possible accompanying morphological changes in the VHC synapses have not yet been systematically examined. We investigated the effects of maturation and aging on the ultrastructure of the ribbon-type AZs in murine utricles using various electron microscopic techniques and combined them with confocal and super-resolution light microscopy as well as metabolic imaging up to 1 year of age. In older animals, we detected predominantly in type I VHCs the formation of floating ribbon clusters, mostly consisting of newly synthesized ribbon material. Our findings suggest that VHC ribbon-type AZs undergo dramatic structural alterations upon aging.


Visual outcome after paediatric cataract surgery: is age a major factor?
To determine functional results after unilateral and bilateral cataract surgery in children with different aphakic optical correction. In this retrospective study, we evaluated visual acuity and binocular vision in 107 children who underwent cataract surgery during the 10 year period from 1985 to 1995. Aphakia was corrected by an intracapsular intraocular lens (IOL), spectacles or contact lenses. Mean visual acuity was > 20/40 (< 0.3 log MAR) with normal binocular vision in 58 children over 7 months of age operated on for bilateral cataracts. Pseudophakic eyes regained visual acuity > 20/63 (< 0.5 log MAR) more often (90%) than aphakic eyes (46%) (p < 0.001). Binocular vision was also achieved more often after IOL implantation (p < 0.001). Visual outcome of early bilateral cataracts was less satisfactory in children with abnormal foveolar function. For 49 children who had surgery for unilateral cataracts, prognosis was poor when surgery was performed before the age of 7 months. For cataract surgery in older children (> or = 7 months) mean visual acuities were better with IOL implantation (p < 0.05). Cataract surgery with unilateral and bilateral IOL implantation can provide a beneficial effect on final visual outcome in children who are operated on before abnormal foveolar function develops.


Assembly dynamics and structure of an aegerolysin, ostreolysin A6.
Ostreolysin A6 (OlyA6) is an oyster mushroom-derived membrane-binding protein that, upon recruitment of its partner protein, pleurotolysin B, forms a cytolytic membrane pore complex. OlyA6 itself is not cytolytic but has been reported to exhibit pro-apoptotic activities in cell culture. Here we report the formation dynamics and the structure of OlyA6 assembly on a lipid membrane containing an OlyA6 high-affinity receptor, ceramide phosphoethanolamine, and cholesterol. High-speed atomic force microscopy revealed the reorganization of OlyA6 dimers from initial random surface coverage to 2D protein crystals composed of hexameric OlyA6 repeat units. Crystal growth took place predominantly in the longitudinal direction by the association of OlyA6 dimers, forming a hexameric unit cell. Molecular-level examination of the OlyA6 crystal elucidated the arrangement of dimers within the unit cell and the structure of the dimer that recruits pleurotolysin B for pore formation.


Frequency and function of regulatory T cells after ischaemic stroke in humans.
Ischaemic stroke is an important cause of disability and death. Local inflammation in the brain following stroke is thought to enhance damage. Animal studies show that regulatory T cells (Tregs) can downregulate this inflammation and assist recovery, but there are no previous studies of the function of Tregs in human stroke. The current study aimed to quantify Tregs in peripheral blood following stroke and to investigate their function. Treg numbers were significantly increased after stroke, particularly in males. However, the functional capacity of Tregs to inhibit proliferation of autologous cells at low ratios of Treg to responder cells was reduced, particularly in female patients, compared to controls. This study is the first to report gender-specific changes in the numbers and function of Tregs after ischaemic stroke. These changes may affect stroke outcome.


Dalitong granule combined with electroacupuncture in the treatment of functional dyspepsia: A randomized controlled trial.
To explore clinical short and long-term effect of combining dalitong granule (DG) and electroacupuncture group (EA) in the treatment of functional dyspepsia. Totally 640 patients with confirmed functional dyspepsia were randomly divided into 4 groups using a randomized digital table: the DG group, the EA group, the combined group and the control group, 160 cases in each group. The DG group was treated with 6 g DG 3 times daily; the EA group was treated with puncture of points Zusanli (ST36), Zhongwan (CV12), Neiguan (PC6), Taichong (LR3) and Gongsun (SP4) twice daily; the combined group with above-mentioned DG and EA; and the control group with 5 mg mosapride 3 times, 20 mg pantoprazole and 25 mg amitriptylines twice daily. The treatment course was 4 weeks for all groups. The symptom score, quality of life score by Short Form 36 Health Survey Questionnaires (SF-36), plasma motilin by radioimmunoassay, electrogastrographic frequencies by electrogastrogram (EGG) and gastric emptying by B-sonography were examined, and adverse reactions were observed before, at the end of treatment and 60 weeks post-treatment. In the DG group 1 case dropped out for not taking medicine strictly and 1 case was lost to follow-up, while 1 case in the EA group and 2 cases in the combined therapy group were lost to follow-up. Compared with pre-treatment, quality of life score, plasma motilin, electrogastrographic frequencies and gastric emptying were all increased significantly, while symptom score was decreased significantly at the end of treatment in each group (P<0.01); in the combined group quality of life score, plasma motilin, electrogastrographic frequencies and gastric emptying were all significantly higher than those in the other groups, while symptom score was significantly lower than in the other groups (P<0.05). Compared with at the end of treatment, these indices changed insignificantly in the combined group and the EA group 60 weeks post-treatment (P>0.05), but the 4 increased indices were all decreased significantly, and symptom score was increased significantly in the DG and the control groups (P>0.05). The short and long-term total effective rates in the combined group were all significantly higher than those in the other treatment groups (P<0.05 or P<0.01). No serious adverse reaction occurred in the four groups. Combined treatment of DG and EA could increase both plasma motilin and electrogastrographic frequencies, promote gastric emptying, alleviate the symptom of dyspepsia so as to increase quality of life, with better safety and long-term effect.


Emphysema in asymptomatic smokers: quantitative CT evaluation in correlation with pulmonary function tests.
To provide quantitative information on emphysema in asymptomatic smokers in correlation with pulmonary function tests (PFT). The study population included 75 smokers (current smokers: n=39; ex-smokers: n=36) and 25 nonsmokers who underwent volumetric high-resolution CT of the chest with automated quantification of emphysema and PFTs. Current smokers had a higher percentage of emphysema in the right lung (P=0.041) and right upper lobe (P=0.037). The overall percentage of emphysema did not differ according to the Gold stage (P=0.77). Smokers with emphysema had significantly higher mean values of FRC (P=0.012), RV (<0.0001) and TLC (P=0.0157) than smokers without emphysema but no significant differences were found in neither the mean values of TLCO nor in expiratory flows (P>0.05). Correlations were found between the percentage of emphysema and (a) cigarette consumption of current (r=0.34215; P=0.0330) and ex-smokers (r=0.44104; P=0.0071); and (b) alterations of TLC, FRC, RV and DLCO of smokers. Quantitative CT allows recognition of regional specificities and subclinical functional alterations in smokers with emphysema.


Using network analysis to localize the epileptogenic zone from invasive EEG recordings in intractable focal epilepsy.
Treatment of medically intractable focal epilepsy (MIFE) by surgical resection of the epileptogenic zone (EZ) is often effective provided the EZ can be reliably identified. Even with the use of invasive recordings, the clinical differentiation between the EZ and normal brain areas can be quite challenging, mainly in patients without MRI detectable lesions. Consequently, despite relatively large brain regions being removed, surgical success rates barely reach 60-65%. Such variable and unfavorable outcomes associated with high morbidity rates are often caused by imprecise and/or inaccurate EZ localization. We developed a localization algorithm that uses network-based data analytics to process invasive EEG recordings. This network algorithm analyzes the centrality signatures of every contact electrode within the recording network and characterizes contacts into susceptible EZ based on the centrality trends over time. The algorithm was tested in a retrospective study that included 42 patients from four epilepsy centers. Our algorithm had higher agreement with EZ regions identified by clinicians for patients with successful surgical outcomes and less agreement for patients with failed outcomes. These findings suggest that network analytics and a network systems perspective of epilepsy may be useful in assisting clinicians in more accurately localizing the EZ.


HI-6 modulates immunization efficacy in a BALB/c mouse model.
HI-6 is used as an antidote to nerve agents. It can also act as an antagonist to acetylcholine receptors (AChRs) including the nicotinic receptor, α 7 nAChR which is involved in regulating the immune response through macrophages. This experiment investigated the efficacy of HI-6 to regulate the immune response. Laboratory BALB/c mice received HI-6 and/or keyhole limpet hemocyanin (KLH) as an antigen. Antibody production was investigated after either 21 or 65 days when either single or repeated dose of antigen was applied. We confirmed that HI-6 significantly improved vaccination efficacy when KLH was given in a dose of 1mg/kg. The effect was dose dependent. A combination of HI-6 and KLH produced a vaccination of almost the same efficacy as that for Freund's complete adjuvant. The findings point at the suitability of HI-6 for improving vaccination efficacy at the level of immunity regulation by the nervous system.


Co-registration of x-ray and MR fields of view in a hybrid XMR system.
To validate one possible function of a real-time x-ray/MR (XMR) interface in a hybrid XMR system using x-ray images as "scouts" to prescribe the MR slices. The registration process consists of two steps: 1) calibration, in which the system's geometric parameters are found from fiducial-based registration; and 2) application, in which the x-ray image of a target structure and the estimated geometric parameters are used to prescribe an MR slice to observe the target structure. Errors from the noise in the location of the fiducial markers, and MR gradient nonlinearity were studied. Computer simulations were used to provide guidelines for fiducial marker placement and tolerable error estimation. A least-squares-based correction method was developed to reduce errors from gradient nonlinearity. In simulations with both sources of errors and the correction for gradient nonlinearity, the use of 16 fiducial markers yielded a mean error of about 0.4 mm over a 7200 cm(3) volume. Phantom scans showed that the prescribed target slice hit most of the target line, and that the length visualized was improved with the least-squares correction. The use of 16 fiducial markers to co-register XMR FOVs can offer satisfactory accuracy in both simulations and experiments.


Elevated plasma homocysteine was associated with hemorrhagic and ischemic stroke, but methylenetetrahydrofolate reductase gene C677T polymorphism was a risk factor for thrombotic stroke: a Multicenter Case-Control Study in China.
It is still controversial whether elevated plasma homocysteine and the C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene are risk factors for stroke. The aim of the present study was to investigate the association between the 2 factors and stroke in Chinese in a large case-control study. We recruited 1823 stroke patients (807 cerebral thrombosis, 513 lacunar infarction, 503 intracerebral hemorrhage) and 1832 controls. Total plasma homocysteine was determined by high-performance liquid chromatography. C677T polymorphism was genotyped by polymerase chain reaction and HinfI digestion. Total plasma homocysteine levels were significantly higher in cases than controls (median, 14.7 versus 12.8 micromol/L; P<0.001) and associated with an increased risk of 1.87-fold (95% confidence interval [CI], 1.58 to 2.22) for overall stroke, 1.72-fold (95% CI, 1.39 to 2.12) for cerebral thrombosis, 1.89-fold (95% CI, 1.50 to 2.40) for lacunar infarction, and 1.94-fold (95% CI, 1.48 to 2.55) for intracerebral hemorrhage. The C677T mutation of the MTHFR gene was positively correlated with plasma homocysteine levels in both controls (beta=0.250, P<0.001) and cases (beta=0.272, P<0.001) and more frequently in cases than in controls (47.0% versus 44.2%, P=0.017). The TT genotype was associated with an increased risk for overall stroke (odds ratio, 1.27; 95% CI, 1.04 to 1.56) and thrombotic stroke (odds ratio, 1.37; 95% CI, 1.06 to 1.78). The C677T polymorphism of the MTHFR gene was associated with increased risk of cerebral thrombotic stroke in Chinese. Total plasma homocysteine was correlated with both ischemic and hemorrhagic stroke, suggesting potential initiation of homocysteine-lowering therapy in this population.


A unique and effective method of anatomy education: Small-group learning with prosected plastinated specimens.
At the New York University College of Dentistry, we are faced with the challenge of teaching Head and Neck Anatomy to a class of approximately 380 first-year students. We have developed an innovative anatomy curriculum that has proven effective in facilitating students' learning and long-term retention of the material. It has the added benefit of being time- and cost-efficient. Here, we share the structure of our curriculum and examine the student outcomes and student feedback. In this paper, we describe the evidence-based methods used in our course and present measures of student success. We also surveyed students about aspects of the anatomy curriculum. Our curriculum efficiently manages cost, instructional time, and classroom space, while promoting student success. Over the last 9 years, NYU Dentistry students have achieved a mean first-time pass rate of 98.6% and an average anatomy score of 1.74 standard deviations above the national mean on the National Board Dental Examination Part I. Students agree with instructor assessments of which features of the curriculum are valuable and state that the course helps them prepare for clinical courses. We believe that the main factors in the success of our course are the small group setting, the benefits of spaced repetition and frequent quizzes, and the use of plastinated specimens in place of wet cadavers.


Liver transplantation in neonates.
Orthotopic liver transplantation (OLT) has evolved over the past two decades to become the standard of care for end-stage liver disease in infants and children. Technical advances, particularly the use of technical variant allografts, have permitted extension of OLT into a much younger and smaller population than previously possible. Major centers around the world now routinely perform OLT in infants with survival success equivalent to that in older children and adults. We are beginning to see a small population of school-aged children who were infant OLT recipients. The further extension of OLT into neonates is more recent, with only a few pediatric centers reporting survival success. Very little is known about this frontier of transplantation. Our intent is to provide an overview of neonatal OLT using all available data and our experience in the field.


Behavioral reactivity to stress: amplification of stress-induced noradrenergic activation elicits a galanin-mediated anxiolytic effect in central amygdala.
Brain norepinephrine (NE) modulates many aspects of the stress response. The interaction between NE and neuropeptides such as galanin, with which it is closely associated and which may be released from noradrenergic terminals under conditions of high activity, has not been well studied. We therefore investigated the modulatory effects of galanin in the central nucleus of the amygdala (CeA) on behavioral responsivity to stress when activation of the noradrenergic system was amplified using the adrenergic autoreceptor antagonist yohimbine (2.5 mg/kg ip). Either immobilization stress or yohimbine alone had anxiogenic effects on rat behavior in the elevated plus maze. However, yohimbine pretreatment before stress produced a paradoxical anxiolytic response, which we hypothesized was attributable to galanin release in CeA. Microdialysis verified that yohimbine amplified NE release in CeA during immobilization stress, and also showed that whereas there was no detectable change in galanin release in CeA during stress alone, there was an increase during immobilization stress after yohimbine pretreatment. Bilateral administration of the galanin antagonist M40 into CeA before stress blocked the anxiolytic influence of yohimbine pretreatment. Exogenous galanin mimicked the anxiolytic effect of yohimbine pretreatment, and this too was blocked by M40. These results suggest that amplifying the noradrenergic response to stress can recruit galanin release in CeA, which buffers the anxiety-like behavioral response to acute stress. The balance between noradrenergic and peptidergic neurotransmission may be modified by prior stress, drug treatment or genetic variability, and may represent a novel target for treatment of stress-related neuropsychiatric disorders.


YAP1 promotes multidrug resistance of small cell lung cancer by CD74-related signaling pathways.
Our previous research found that YAP1 may have a role in multidrug resistance (MDR) in small cell lung cancer (SCLC). However, its underlying mechanism is unknown. In this study, we investigated the expression of YAP1 using immunohistochemical staining and assessed the relationship between the expression of YAP1 and overall survival in patients with SCLC. We established H69 stable cell lines that overexpressed constitutively active YAP1 and H446 stable cell lines that dominate negative YAP1. We conducted CCK-8, flow cytometric analysis, and in vivo chemosensitivity experiments to evaluate the function of YAP1 in drug sensitivity apoptosis in vitro and in vivo. The results indicated that patients with high YAP1 expression have shorter survival rates and more advanced disease stage than those with low YAP1 expression. YAP1 may induce MDR by inhibiting the apoptosis of SCLC. YAP1 induced MDR when YAP1 was hyperactivated, and drug sensitivity increased when YAP1 was inhibited in vitro and in vivo. CD74 was significantly correlated with YAP1 in SCLC samples. Inhibition of CD74 using ISO-1 increased drug sensitivity significantly. The expression of YAP1 is significantly correlated with overall survival and disease stage in patients with SCLC. YAP1 may play an important role in these patients. We were the first to report that YAP1 can induce MDR in SCLC in vitro and in vivo. CD74 may be involved in YAP1-induced MDR.


Novel pit and fissure sealant containing nano-CaF2 and dimethylaminohexadecyl methacrylate with double benefits of fluoride release and antibacterial function.
Pit and fissure sealants with antibacterial and remineralization properties have broad application prospects in caries prevention. The objectives of this study were to: (1) develop a novel pit and fissure sealant containing CaF2 nanoparticles (nCaF2) and dimethylaminohexadecyl methacrylate (DMAHDM); and (2) investigate the effects of nCaF2 and DMAHDM on biofilm response and fluoride (F) ion release for the first time. Helioseal F was used as a control. Bioactive sealants were formulated with DMAHDM and nCaF2. Flow properties, enamel shear bond strength, hardness and F ion releases were measured. Streptococcus mutans (S. mutans) biofilms were grown on sealants. Biofilm metabolic activity, lactic acid production, colony-forming units (CFU), and pH of biofilm culture medium were measured. Adding 5% DMAHDM and 20% nCaF2 did not reduce the paste flow and enamel bond strength, compared to control (p < 0.05). Hardness of sealants with 20% nCaF2 and DMAHDM was higher than control (p < 0.05). The F ion release from 20% nCaF2 was much higher than that of commercial control (p < 0.05). The sealant with DMAHDM reduced the S. mutans biofilm CFU by 4 logs. The pH in biofilm medium of the new bioactive sealant was much higher (pH 6.8) than that of commercial sealant (pH 4.66) (p < 0.05). The new bioactive pit and fissure sealant with nCaF2 and DMAHDM achieved high fluoride release and strong antibacterial performance. This novel fluoride-releasing and antibacterial sealant is promising to inhibit caries and promote the remineralizaton of enamel and dentin.


Minimally Invasive Sampling Method Identifies Differences in Taxonomic Richness of Nasal Microbiomes in Young Infants Associated with Mode of Delivery.
To date, there is a limited understanding of the role of the airway microbiome in the early life development of respiratory diseases such as asthma, partly due to a lack of simple and minimally invasive sample collection methods. In order to characterize the baseline microbiome of the upper respiratory tract (URT) in infants, a comparatively non-invasive method for sampling the URT microbiome suitable for use in infants was developed. Microbiome samples were collected by placing filter paper in the nostrils of 33 healthy, term infants enrolled as part of the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure (INSPIRE) study. After bacterial genomic DNA was extracted from the filters, amplicons were generated with universal primers targeting the V1-V3 region of the 16S rRNA gene. This method was capable of capturing a wide variety of taxa expected to inhabit the nasal cavity. Analyses stratifying subjects by demographic and environmental factors previously observed or predicted to influence microbial communities were performed. Microbial community richness was found to be higher in infants who had been delivered via Cesarean section and in those who had been formula-fed; an association was observed between diet and delivery, which confounds this analysis. We have established a baseline URT microbiome using a non-invasive filter paper nasal sampling for this population, and future studies will be performed in this large observational cohort of infants to investigate the relationship between viral infections, the URT microbiota, and the development of childhood wheezing illnesses.


Donatio organorum- reluctance to organ donation medical students; a cross-sectional descriptive study.
Organ donation is the act of removing an organ or tissue from a donor and transplanting the said organ/tissue to a recipient. Despite being the only definitive treatment for end-organ failure, there is a lot of hesitation surrounding the practice of organ donation. Even among medical students, who are more aware of the benefits of organ donation than the general public, this reluctance is widespread.Therefore, we conducted this research to determine the basis of this skepticism, so that the root causes can be identified and eradicated. Our research sought to ascertain the overall attitudes of Rawalpindi Medical University, Pakistan's students towards organ donation, the associated factors that influenced this attitude (religious devotion, gender, age, year of study) and the reasons for the hesitance. A cross-sectional study targeting the students of first to final year MBBS was conducted at Rawalpindi Medical University, Pakistan in the year 2022. The sample size was calculated using OpenEpi software, and came out to be 292. The students enrolled at Rawalpindi Medical University during the year 2021-2022 were made a part of the study. A self-structured questionnaire that was developed after substantial research was used to collect the data using a non-random convenience sample technique. Chi Square test was used to determine significance after data analysis using SPSS-22. A total of 290 students participated in the study, 58 from each year. All of the participants were Muslim. A very strong correlation was found between high devoutness and willingness towards organ donation (p = 7.4252E-13). Only 9/290 (3%) of people in Pakistan have joined The Transplantation Society of Pakistan; the main cause of this low ratio is that very few people were aware that such a group even existed (according to 62% of the responders). The mistrust of doctors and the belief that appropriate efforts would not be done to resuscitate patients who have signed up for organ donation is a significant factor in the anxiety surrounding organ donation. There are several reasons why people are reluctant to donate their organs, including a lack of understanding of religious perspectives on the subject, mistrust of medical professionals and medical administration, and general public ignorance. We can make a significant progress toward closing the gap between the demand for and supply of organ donations if these problems are remedied. The most effective strategy to stop organ trafficking is through organ donation. Through seminars, conversations, and workshops, we need to raise awareness about organ donation.


Structural evaluation of probucol nanoparticles in water by atomic force microscopy.
Structural evaluation of probucol nanoparticles coground with polyvinylpyrrolidone K17 and sodium dodecyl sulfate for 90 min was performed by solid-state nuclear magnetic resonance (NMR) spectroscopy and atomic force microscopy (AFM) with force-distance curve analysis. The results of solid-state NMR indicated that the cogrinding changed crystalline probucol to amorphous form. The number-averaged mean heights of probucol particles in the ground mixture (GM) suspension were determined by AFM to be 6 and 15 nm for freshly prepared and 24h-stored samples, respectively. Nucleation and the subsequent crystal growth might have occurred after the GM was dispersed in water. The presence of probucol nanocrystals and agglomeration of the primary probucol nanoparticles were recognized by AFM force-distance curve analysis. AFM could be a promising tool to evaluate the structure of nanoparticles as well as their agglomeration behavior in aqueous media.


Treatment of metastatic castration resistant prostate cancer with radium-223: a retrospective study at a US tertiary oncology center.
Guidelines for optimal sequencing of radium-223 and chemotherapy for metastatic castration resistant prostate cancer (mCRPC) do not exist. This study evaluated treatment patterns and overall survival (OS) among patients with mCRPC treated with radium-223 in an academic clinical setting. A retrospective study was conducted of bone metastases-predominant mCRPC patients treated with radium-223. Treatment patterns from 2013 to 2018 were evaluated in patients treated with radium-223 pre- vs. post-chemotherapy. OS was examined using Kaplan-Meier medians and 95% confidence intervals. In total, 220 patients were treated with radium-223 (64 pre-chemotherapy, 83 post-chemotherapy, 73 no chemotherapy). Mean radium-223 injections per patient was 5.3 and 4.3 in the pre- vs. post-chemotherapy cohorts, respectively (p < 0.001). The number of chemotherapy cycles was similar for chemotherapy given pre- or post-radium-223. Mean line of mCRPC therapy of radium-223 was 3rd and 5th when given pre- and post-chemotherapy, respectively (p < 0.001). 41.8% patients were treated with radium-223 in combination with another mCRPC therapy, commonly abiraterone acetate (43.5%) or enzalutamide (52.2%). The majority received combination therapy for the duration of radium-223 treatment; 20.7% started another agent after radium-223 initiation; 20.7% initiated radium-223 while on established therapy. Median OS from first mCRPC treatment was 39.4 months (95% CI 33.0, 48.8) for patients with radium-223 pre-chemotherapy vs. 37.4 months (95% CI 32.0, 43.5) post-chemotherapy (and 35.2 months [95% CI 27.9, 43.3] vs. 32.0 months [95% CI 26.9, 36.0] for patients with radium-223 combination vs. monotherapy). This retrospective analysis of patients treated with radium-223 demonstrates that administration of radium-223 pre-chemotherapy increased likelihood of completion of radium-223 treatment. Radium-223 given pre- or post-chemotherapy and with or without combination therapy did not result in significant differences in OS. Additional studies are needed to determine the optimal sequencing strategy of mCRPC in the modern era.


Cyclic AMP increase the Na+ permeability of the avian erythrocyte membrane by a process which does not involve protein phosphorylation.
Preparations of avian erythrocyte plasma membranes have been made which are in the form of sealed vesicles. Using these preparations the permeability of the membranes to N+, K+, Mg2+ and Ca2+ was measured. Monobutyryl cyclic AMP and cyclic AMP increased the permeability to Na+ and Ca+ under conditions where no protein phosphorylation could occur. The only effect of phosphorylation of membrane proteins was to reduce Ca+ permeability. It is thus concluded that cyclic AMP increases Na+ permeability in the avian erythroycte by a direct effect which does not involve protein phosphorylation.


T-helper cell regulation of CD45 phosphatase activity by galectin-1 and CD43 governs chronic lymphocytic leukaemia proliferation.
Chronic lymphocytic leukaemia (CLL) is characterised by malignant mature-like B cells. Supportive to CLL cell survival is chronic B-cell receptor (BCR) signalling; however, emerging evidence demonstrates CLL cells proliferate in response to T-helper (Th) cells in a CD40L-dependent manner. We showed provision of Th stimulation via CD40L upregulated CD45 phosphatase activity and BCR signalling in non-malignant B cells. Consequently, we hypothesised Th cell upregulation of CLL cell CD45 activity may be an important regulator of CLL BCR signalling and proliferation. Using patient-derived CLL cells in a culture system with activated autologous Th cells, results revealed increases in both Th and CLL cell CD45 activity, which correlated with enhanced downstream antigen receptor signalling and proliferation. Concomitantly increased was the surface expression of Galectin-1, a CD45 ligand, and CD43, a CLL immunophenotypic marker. Galectin-1/CD43 double expression defined a proliferative CLL cell population with enhanced CD45 activity. Targeting either Galectin-1 or CD43 using silencing, pharmacology, or monoclonal antibody strategies dampened CD45 activity and CLL cell proliferation. These results highlight a mechanism where activated Th cells drive CLL cell BCR signalling and proliferation via Galectin-1 and CD43-mediated regulation of CD45 activity, identifying modulation of CD45 phosphatase activity as a potential therapeutic target in CLL.


A highly sensitive sensor based on a computer-designed magnetic molecularly imprinted membrane for the determination of acetaminophen.
In this paper, a sensor based on a magnetic surface molecularly imprinted membrane (MMIP) was prepared for the highly sensitive and selective determination of acetaminophen (AP). Before the experiment, the appropriate functional monomers and solvents required for the polymer were screened, and the molecular electrostatic potentials (MEPs) were calculated by the DFT/B3LYP/6-31 + G method. MMIP with high recognition of AP was synthesized based on Fe3O4@SiO2nanoparticles (NPs) with excellent core-shell structure. Next, a carbon paste electrode (CPE) was filled with a piece of neodymium-iron-boron magnet to make magnetic electrode (MCPE), and MMIP/MCPE sensor was obtained by attaching a printed polymer to the surface of the electrode under the strong magnetic. Due to the stable molecular structure of the electrode surface, the sensor is highly effective and accurate for detection of AP using DPV. The DPV response of the sensor exhibited a linear dependence on the concentration of AP from 6 × 10-8 to 5 × 10-5 mol L-1 and 5 × 10-5 to 2 × 10-4 mol L-1, with a detection limit based on the lower linear range of 1.73 × 10-8 mol L-1(S/N = 3). When used for determination of AP in actual samples, the recovery of the sensor to the sample was 95.80-103.76%, and the RSD was 0.78%-3.05%.


First identification of four trypanorhynchid cestodes: Callitetrarhynchus speciouses, Pseudogrillotia sp. (Lacistorhynchidae), Kotorella pronosoma and Nybelinia bisulcata (Tentaculariidae) from Sparidae and Mullidae fish.
Four previously unrecognized trypanorhynchids are described based on fish specimens from Sparidae and Mullidae host fish of the Red Sea. From September 2010 to June 2011, 66 specimens of the sea bream Pagrus pagrus (F: Sparidae) and 43 of the red mullet Mullus barbatus (F: Mullidae) were purchased from markets in the Suez and Hurghada cities of the Red Sea. The fishes were measured, and their organs investigated for helminth infections. Forty-one (37.6 %) out of the 109 fish specimens investigated were parasitized with Trypanorhyncha metacestodes, identified as Callitetrarhynchus speciouses Linton 1897, Pseudogrillotia sp. Dollfus 1969, Kotorella pronosoma Stossich 1901 from P. pagrus, and Nybelinia bisulcata Linton 1889 from M. barbatus in the mesentery and peritoneal cavity, with prevalences of 16.5, 11.0, 6.0, and 12.0 %. All of these larval stages were encapsulated larvae in blastocysts. C. speciouses is characterized by an elongated scolex, two bothria, a long postbulbosa, and four elongated bulbs. Pseudogrillotia sp. possesses a scolex with two lateral patelliform bothridia; posterior margins are free, not notched. A long sheath was observed, which was irregularly coiled when tentacles invaginated. N. bisulcata possesses an acraspedote scolex with four bothridia, which are broad, bean-shaped. The tentacles are spirally coiled, supplied with hooks with abruptly turned points. The four tentacles sheaths rose from scolex as two anterior (front) and two posterior (back) which overlap at the apices of bulbs. K. pronosoma is characterized by a short body with a craspedote scolex and four bothridia. The tentacles are short and emerge pairwise. The presence of Trypanorhyncha metacestodes in the muscles does not represent a risk of infection for humans. They have a negative effect on fish esthetics. The repugnant aspect and the prohibition for commercial use by sanitary inspectors, however, cause consumer rejection. Parasites of the order Trypanorhyncha have been recorded in these host fishes for the first time.


Medical Students' Perceptions on the Role of Pharmacists.
Over the last decade, the pharmacists' role in health-care services has evolved and expanded to include more direct patient care and disease management services. To evaluate medical students' perceptions on pharmacists, their role in health care, and demographic or experiential factors that influenced the medical students' opinions. Medical students, at a Midwest, academic medical center, were solicited to complete a cross-sectional, web-based survey consisting of 3 domains: basic demographics, knowledge of the pharmacy profession, and opinions of pharmacists. Participants supported pharmacists' role in recommending and monitoring drug therapy. However, participants did not support pharmacists' role in performing physical examinations, health screenings, or managing patients with chronic diseases. The main factors that influenced perceptions of pharmacists were female gender and frequent (weekly or more) interaction with a pharmacist or pharmacy student. Neither year in medical school nor participation in intercollaborative practice significantly influenced perceptions of pharmacists. This survey highlights the need to improve the education medical students receive about pharmacists' contribution to the health-care team and the importance of increasing the interaction between medical students and pharmacists or pharmacy students to enhance interprofessional collaboration.


Down-regulation of genes related to the adrenergic system may contribute to splanchnic vasodilation in rat portal hypertension.
Splanchnic vasodilation initiates the hyperdynamic syndrome in portal hypertension. We aimed to explore molecular mechanisms involved in the development of mesenteric vasodilation in portal hypertension. Superior mesenteric artery (SMA) samples from portal vein ligated (PVL) and sham rats were compared in a time course experiment using DNA microarrays. Selected genes were quantified by qRT-PCR in PVL and cirrhotic rats. Inmunohistochemistry of tyrosine hydroxylase (Th) and norepinephrine was assessed in SMA sections of PVL and sham rats. Western blot analysis of Th, dopamine beta-hydroxylase (Dbh) and synaptosome-associated protein (Snap-25) was performed in SMA and jejunum samples from the animal models. Fifty differentially expressed genes implicated in neurotransmission, especially adrenergic, were detected in SMA samples from PVL rats. Sequential analysis showed a profound down-regulation at 14 days in PVL rats. These down-regulated genes were confirmed by RT-PCR in SMA from PVL and cirrhotic rats. Th and NE detection by immunohistochemistry was reduced in PVL compared to sham. Th, Dbh and Snap-25 expression was lower in SMA from 14-day PVL and cirrhotic rats compared to sham and control rats, respectively. Genetic down-regulation of genes related to the adrenergic system might have a role in splanchnic vasodilation of portal hypertension.


Identification and sensitivity of two rare fungal species isolated from two patients with Fusarium keratomycosis.
We report two cases of Fusarium keratomycosis in which molecular analysis was used to identify two rare causative Fusarium species. A 65-year-old woman was diagnosed with Fusarium keratomycosis caused by F. equiseti, confirmed by sequencing the internal transcribed spacer (ITS) region and morphological characteristics. She was initially treated with topical corticosteroid but the keratitis did not improve. Even after aggressive antifungal treatment, there was a severe reduction of vision. In the end, the eye perforated. Our second case was a 75-year-old man who had diabetes mellitus. He developed keratitis after his cornea was injured by corn stalks. The ITS region identified the causative organism as F. verticillioides. Unlike the first case, he had good visual recovery after early antifungal therapy. Our findings demonstrate that both ITS and morphological characteristics can be used to identify the exact Fusarium species causing Fusarium keratomycosis. This allowed us to determine the sensitivity of these species to antifungal drugs that can be used to treat patients with these species of Fusarium.


The rise and fall of cot sides.
Some researchers have questioned the use of cot sides, citing evidence that the incorrect use of them might be considered dangerous and even unethical. This article looks at some of the literature on the subject and discusses the results of an audit which was carried out in a large district general hospital last year.


Ano-rectovaginal fistula after obstetrical anal sphincter injury: Diverting stoma does not improve the surgical results.
Ano-rectovaginal fistulas (ARVF) are challenging for the surgeon. Most of the series mix aetiologies, leading to confusion with respect to the conclusion. The aim of this study was to assess the factors associated with the success of ARVF management following obstetrical anal sphincter injury (OASIS). This retrospective multicentric study included all the patients undergoing surgery for ARVF identified by the hospital codes. Patients for whom the aetiology of ARVF was not OASIS were excluded. The major outcome measure was the success of the procedure. Sixty patients with treated ARVF due to OASIS were identified. The success of overall management was 91.7%. Female patients underwent a mean of 2.5 (±1.7) procedures. A diverting stoma was formed in 29 patients (48.3%) of which 26 were closed at the end of the management period (89.7%). Of the 148 surgical procedures, only 55 were successful (37.2%). The order of the procedures (OR = 1.38; 95% CI: 0.75-2.51) or the diverting stoma (OR = 1.46; 95% CI: 0.31-6.91) were not significantly associated with the success of the surgery. However, Martius flap (OR = 4.13; 95% CI: 1.1-15.54) and Musset procedures (OR = 5.79; 95% CI: 1.77-18.87) produced better results than the endorectal advancement flap (ERAF). The other procedures did not show a significant correlation with management success. A diverting stoma is not mandatory in the management of ARVF due to OASIS to improve the success of the surgical procedure. While the Martius flap procedure offers better results, the ERAF procedure may be preferred as a primary intervention in the absence of sphincter injury as it is less invasive. In cases of residual sphincter injury, the Musset procedure is most likely to be the best option.


Effect of acute and chronic ethanol treatment on renal prostaglandins in the rat.
To study the effects of ethanol on renal prostaglandins (PGs), we gave rats a dose of 3.0 g/kg body weight either as a single IP injection (acute treatment) or daily IP injections of the same dose for 23 consecutive days (chronic treatment). The availability of PG precursors was evaluated from the post mortem accumulation of PGF2 alpha in kidney as determined by gas chromatography-mass spectrometry, and the renal excretion of PGF2 alpha was measured by radioimmunoassay. Acute ethanol treatment had no dramatic effect on either tissue levels or urinary excretion rate of PGF2 alpha but chronic ethanol treatment significantly lowered renal PGF2 alpha levels. In another experiment we employed liquid ethanol diets and a pair feeding technique for 12 days to achieve tolerance and physical dependence on ethanol. The levels of PGF2 alpha and 6-keto PGF1 alpha were measured in kidney in rats killed at 2, 6, and 12 days post-treatment. The kidney levels of both prostaglandins were lowered throughout the period of chronic ethanol exposure but returned to normal within five days after withdrawal. Thus, chronic but not acute ethanol treatment leads to a depletion of the renal stores of prostaglandin precursors in the rat.


Development of vascularized nerve scaffold using perfusion-decellularization and recellularization.
Vascularized nerve grafts (VNG) may offer an advantage in peripheral nerve regeneration by avoiding ischemic damage and central necrosis observed in non-VNG, particularly for the treatment of large and long nerve defects. However, surgical complexity, donor site morbidity and limited nerve availability remain important drawbacks for the clinical use of VNG. Here we explore the potential of perfusion-decellularization for bioengineering a VNG to be used in peripheral nerve reconstruction. Porcine sciatic nerves were surgically procured along with their vascular pedicle attached. The specimens were decellularized via perfusion-decellularization and preservation of the extracellular matrix (ECM), vascular patency and tissue cytokine contents were examined. Scaffold reendothelialization was conducted with porcine aortic endothelial cells in a perfusion-bioreactor. Morphologic examination of decellularized VNG and analysis of the DNA content demonstrated cell clearance whereas ECM content and structures of the nerve fascicles were preserved. Using 3D micro-computed tomography imaging we observed optimal vasculature preservation in decellularized scaffolds, down to the capillary level. Cytokine quantification demonstrated measurable levels of growth factors after decellularization. Endothelial cell engraftment of the large caliber vessels was observed in reendothelialized scaffolds. In this study we provide evidence that perfusion-decellularization can be used to create vascularized nerve scaffolds in which the vasculature and the ECM component are well preserved. As compared to non-vascularized conduits, engineered vascularized nerve scaffolds may represent an ideal approach for promoting better nerve regeneration in larger nerve defect reconstructions.


Corticotropin releasing factor in the median raphe nucleus is involved in the retrieval of fear memory in rats.
In the present study, we examined the role of corticotropin releasing factor (CRF) in the median raphe nucleus (MRN) on fear-related behaviors in rats. We employed the contextual fear conditioning test and the elevated plus maze test as memory-dependent and -independent tasks, respectively. Human/rat CRF (10 ng) in 0.5 microl saline was injected into the MRN. Administration of CRF significantly increased memory dependent, but not independent, fear expression. These results suggest that CRF release in the MRN is involved in the retrieval of fear memory.


Genome-wide association analysis of 19,629 individuals identifies variants influencing regional brain volumes and refines their genetic co-architecture with cognitive and mental health traits.
Volumetric variations of the human brain are heritable and are associated with many brain-related complex traits. Here we performed genome-wide association studies (GWAS) of 101 brain volumetric phenotypes using the UK Biobank sample including 19,629 participants. GWAS identified 365 independent genetic variants exceeding a significance threshold of 4.9 × 10-10, adjusted for testing multiple phenotypes. A gene-based association study found 157 associated genes (124 new), and functional gene mapping analysis linked 146 additional genes. Many of the discovered genetic variants and genes have previously been implicated in cognitive and mental health traits. Through genome-wide polygenic-risk-score prediction, more than 6% of the phenotypic variance (P = 3.13 × 10-24) in four other independent studies could be explained by the UK Biobank GWAS results. In conclusion, our study identifies many new genetic associations at the variant, locus and gene levels and advances our understanding of the pleiotropy and genetic co-architecture between brain volumes and other traits.


Molecular targeting of Bcl-2 overcomes prostate cancer cell adaptation to XIAP gene downregulation.
X-linked inhibitor of apoptosis (XIAP) is a suppressor of apoptosis that supports an increased survival and resistance to chemotherapy of human prostate cancer (PCa) cells. Effects of transient (24 h) and chronic (beyond 1 month) downregulation of XIAP in DU145 hormone refractory prostate cancer (HRPC) cells were studied. We found that transient downregulation of XIAP by siRNAs resulted in an increase of apoptosis and a decrease in Bcl-2 levels and sensitized PCa cells to cisplatin. XIAP downregulation by shRNA vector stable transfection led to upregulation of Bcl-2 protein. Our results identify the adaptability of PCa cells to chronic loss of XIAP in part through upregulation of Bcl-2 and indicate that multitargeting approach is the most effective application in the chemotherapy of human HRPC.


Open surgical repair of juxtarenal abdominal aortic aneurysms in the elderly is not associated with increased thirty-day mortality compared with fenestrated endovascular grafting.
Endovascular repair of juxtarenal abdominal aortic aneurysms (JAAAs) with fenestrated grafts (fenestrated endovascular aneurysm repair [FEVAR]) has been reported to decrease operative mortality and morbidity compared with open surgical repair (OSR). However, previous comparisons of OSR and FEVAR have not necessarily included patients with comparable clinical profiles and aneurysm extent. Although FEVAR has often been chosen as the first-line therapy for high-risk patients such as the elderly, many patients will not have anatomy favorable for FEVAR. At present, a paucity of data has examined the operative outcomes of OSR in elderly patients for JAAAs relative to FEVAR. Therefore, we chose to perform a propensity-matched comparison of OSR and FEVAR for JAAA repair in patients aged ≥70 years. Patients aged ≥70 years who had undergone elective nonruptured JAAA repairs from 2012 to 2018 were identified in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) targeted endovascular aneurysm repair (EVAR) and AAA databases. Patients who had undergone FEVAR were identified in the targeted EVAR database as those who had received the Cook Zenith Fenestrated endograft (Cook Medical, Bloomington, Ind). Because our study specifically examined JAAAs, those patients who had undergone OSR with supraceliac proximal clamping or concomitant renal/visceral revascularization were excluded. A 1:1 propensity-match algorithm matched the OSR and FEVAR patients by preoperative clinical and demographic characteristics, operative indications, and aneurysm extent. The 30-day outcomes, including mortality, major adverse cardiovascular events, and pulmonary and renal complications, were compared between the propensity-matched OSR and FEVAR groups. A 1:1 propensity match was achieved, and the final analysis included 136 OSR patients and 136 FEVAR patients. No significant differences were found in 30-day mortality (4.4% vs 3.7%; odds ratio [OR], 1.21; 95% confidence interval [CI], 0.36-4.06; P = .759) between the OSR and FEVAR groups. OSR was associated with a higher incidence of major adverse cardiovascular events compared with FEVAR; however, the trend was not statistically significant (8.1% vs 3.7%; OR, 2.31; 95% CI, 0.78-6.82; P = .131). Compared with FEVAR, the OSR group had significantly greater rates of pulmonary complications (19.1% vs 3.7%; OR, 6.19; 95% CI, 2.30-16.67; P < .001) and renal complications (8.1% vs 2.2%; OR, 3.90; 95% CI, 1.06-14.31; P = .040). In the samples assessed in the present study, the results with OSR of JAAAs in the elderly did not differ from those of FEVAR with respect to 30-day mortality despite a greater incidence of pulmonary and renal complications. Although FEVAR should remain the first-line therapy for JAAAs in elderly patients, OSR might be an acceptable alternative for select patients with anatomy unfavorable for FEVAR.


Effect of head-out water immersion on cardiorespiratory response to dynamic exercise.
Head-out water immersion is known to produce several cardiopulmonary adjustments at rest due to a cephalad shift in blood volume. The purpose of this study was to determine the effect of head-out water immersion on the cardiorespiratory response to graded dynamic exercise. Nineteen healthy middle-aged men performed upright cycling exercise at 40, 60 and 80% of maximal oxygen consumption on land and in water (31.0 +/- 1.0 degrees C) to the shoulders. Cardiac output (measured by the carbon dioxide rebreathing technique) was significantly greater in water at 40 and 80% maximal oxygen consumption. Stroke volume was significantly elevated at all stages of exercise. Heart rate did not differ significantly at 40 and 60% maximal oxygen consumption but was significantly lower in water at 80% maximal oxygen consumption. Total ventilation did not differ significantly in water and on land at any stage of exercise. The results suggest that the central redistribution of blood volume with head-out water immersion leads to an increase in stroke volume. Because there is not a proportional decrease in heart rate with the elevated stroke volume, cardiac output is regulated at a higher level during upright exercise in water compared with that on land. In conclusion, there are serious limitations of available, prerecorded rhythm data bases for designing and testing of automatic external defibrillators. Performance can be adequately assessed only by extensive clinical tests, which seem mandatory for this new and important type of defibrillator.


Male osteoporosis: new trends in diagnosis and therapy.
Osteoporosis is a common condition in men affecting approximately 2 million males in the US. Compared with women, osteoporosis develops later in life and the incidence of osteoporosis-related fractures is lower in men. The morbidity and mortality associated with osteoporotic fractures are much greater in men compared with women, and secondary causes of osteoporosis are more frequently (in approximately 50% of cases) identified in men compared with women with osteoporosis. Excessive alcohol consumption, glucocorticoid excess and hypogonadism are the most commonly identified causes. Primary osteoporosis in men has been linked to changes in sex steroid secretion, the growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis and the vitamin D-parathyroid hormone (PTH) 25-hydroxyvitamin D [25(OH)D]-PTH system. Diagnosing osteoporosis in men is complicated by an ongoing debate on whether to use sex-specific reference values for bone mineral density (BMD) or female reference values. The International Society for Clinical Densitometry recommended using a T score of -2.5 or less of male reference values to diagnose osteoporosis in men who are > or =65 years of age. However, this definition is yet to be validated in terms of fracture incidence and prevalence. Ensuring adequate calcium and vitamin D intake is the cornerstone of any regimen aimed at preventing or treating osteoporosis in men. Bisphosphonates are currently the therapy of choice for treatment of male osteoporosis. A short course of parathyroid hormone (1-34) [teriparatide] may be indicated for men with very low BMD or in those in whom bisphosphonate therapy is unsuccessful. The use of testosterone-replacement therapy for the prevention and treatment of male osteoporosis remains controversial but likely to benefit osteoporotic men with evident hypogonadism.


Urine drug testing for social service agencies. A Canadian experience.
The introduction of urine drug testing for this program has been considered a success by the social services agencies in Nova Scotia for the following reasons: 1. The results of urine drug testing have been accepted by the Family Courts of Nova Scotia because the urine collection and testing are performed with chain of custody procedures from collection to reporting and the analysis includes confirmation of all positive immunoassay screening tests. 2. Urine drug testing (with established screening and confirmation cut-offs) provides an objective indication of recent drug use compared with relying on self-reporting of drug use. 3. Urine drug testing is believed to be a deterrent to drug use because several individuals with a history of drug use have consistently tested negative for 6 to 12 months (30% of the clients). 4. Some clients with a history of substance abuse are successful in becoming drug free with the support of the social workers and the deterrent effect of random drug testing.


Effect of ultrasonic-fed time on combustion and emissions performance in a single-cylinder engine.
In this study, a numerical simulation method for multi-field coupling is proposed in which the ultrasonic is physically fed in the combustion chamber of a gasoline engine. The fine-tuning regulation of activity and reaction paths of gas-liquid two-phase (GLP) fuel is studied by using ultrasonic under in-cylinder complex conditions. The three-dimensional (3D) computational fluid dynamics (CFD) model of the original engine is calibrated, based on the bench test data. The multi-field coupling model of the sound field and combustion field is established by embedding the feature of the sound source surface in the combustion chamber. The ultrasonic with 20 kHz frequency and 100 μm amplitude is fed into the combustion chamber by using the dynamic grid technology. By comparing the simulation results of four ultrasonic-fed schemes (S1∼S4) and ultrasonic-free scheme (No), it is concluded that compared with the No scheme, the average turbulent kinetic energy (TKE) of the schemes S1, S2, and S3 are all increased by 23.2% at the top dead center (TDC), the peak pressure of the schemes S1 and S2 are both increased by 0.58 MPa. The CO and soot formations of scheme S1 are the lowest at 6.5% and 6.1%, respectively, compared with the No scheme. The reasonable use of ultrasonic can promote the fuel oxidation and combustion process, and accelerate the formation of the OH radicals. The ultrasonic-fed has a significantly quantitative control effect on fuel activity and oxidation reaction paths within 10 ms, under the in-cylinder transient and complex combustion condition of the gasoline engine.


Reference ranges for regional cerebral tissue oxygen saturation and fractional oxygen extraction in neonates during immediate transition after birth.
To define reference ranges for regional cerebral tissue oxygen saturation (crSO2) and regional cerebral fractional tissue oxygen extraction (cFTOE) during the first 15 minutes after birth in neonates requiring no medical support. The crSO2 was measured using near infrared spectroscopy (Invos 5100 cerebral/somatic oximeter monitor; Somanetics Corp, Troy, Michigan) during the first 15 minutes after birth for term and preterm neonates. The near infrared spectroscopy sensor was placed on the left forehead. Peripheral oxygen saturation and heart rate were continuously measured by pulse oximetry, and cFTOE was calculated. Neonates were excluded if they required any medical support. A total of 381 neonates were included: 82 term neonates after vaginal delivery, 272 term neonates after cesarean delivery, and 27 preterm neonates after cesarean delivery. In all neonates, median (10th-90th percentiles) crSO2 was 41% (23-64) at 2 minutes, 68% (45-85) at 5 minutes, 79% (65-90) at 10 minutes, and 77% (63-89) at 15 minutes of age. In all neonates, median (10th-90th percentiles) cFTOE was 33% (11-70) at 2 minutes, 21% (6-45) at 5 minutes, 15% (5-31) at 10 minutes, and 18% (7-34) at 15 minutes of age. We report reference ranges of crSO2 and cFTOE in neonates requiring no medical support during transition immediately after birth. The use of cerebral oxygenation monitoring and use of these reference ranges in neonates during transition may help to guide oxygen delivery and avoid cerebral hypo-oxygenation and hyperoxygenation.