Dynamic evaluation of the spinal cord in patients with cervical spondylotic myelopathy using a kinematic magnetic resonance imaging technique.
This prospective study analyzed preoperative and postoperative dynamic changes of the spinal cord in patients with cervical spondylotic myelopathy. (1) To study preoperative kinematic characteristics of the spinal cord in patients with cervical spondylotic myelopathy and compare results with healthy individuals, (2) to understand the dynamic changes of the spinal cord after posterior decompression, and (3) to discover whether the degree of posterior shifting is correlated with surgical outcomes using kinematic magnetic resonance imaging (MRI). Laminoplasty for cervical myelopathy increases the space occupied by the spinal cord leading to a decompressive effect on the cord. However, no consecutive studies have reported the kinematic characteristics of the cervical spine in patients with cervical spondylotic myelopathy both preoperatively and postoperatively. Additionally, there have been no reports investigating the effects of posterior cord shifting in the neutral and maximum flexion and extension positions on surgical outcomes after cervical laminoplasty. Twenty cervical spondylotic myelopathy patients who underwent extensive laminoplasty and 20 healthy individuals were examined. Preoperative and postoperative MRI records were available in all cases. The cervical spines of the subjects were examined in the neutral and maximum flexion and extension positions using an MRI scanner. Sagittal T1-weighted images were obtained at 12 different angles. Images were analyzed for the distance between the dorsal edge of the vertebral column and the center of the cord at each disc level using NIH image software. Average cord distances (L value) in the neutral position and maximum extension position at C4/5 was significantly smaller than those at the other disc levels. The spinal cords of the patients after laminoplasty moved dorsally in the enlarged spinal canal in the neutral position, and in the maximum flexion and extension position. However, the degree of posterior spinal cord shifting was not correlated with surgical outcomes. Cord distances are relatively smaller at C4/5 and C5/6 levels, resulting in a narrowing of the posterior subarachnoid space with posterior cord compression in patients with cervical spondylotic myelopathy. The outcome of surgery was not correlated with the magnitude of postoperative backward shifting of the spinal cord, although the spinal cord of patients after posterior decompression moved significantly dorsally at any of the flexed, neutral, or extended spinal positions. Thus numerous factors might affect the postoperative outcomes.


Newborn screening for hunter disease: a small-scale feasibility study.
Hunter disease (Mucopolysaccharidosis type II, MPS II) is an X-linked lysosomal storage disorder caused by deficiency of iduronate-2-sulfatase (IDS). Two main therapies have been reported for MPS II patients: enzyme-replacement therapy (ERT) and hematopoietic stem-cell transplantation (HSCT). Both treatment modalities have been shown to improve some symptoms, but the results with regard to cognitive functioning have been poor. Early initiation of therapy, i.e., before neurological symptoms have manifested, may alter cognitive outcome. The need for early identification makes Hunter disease a candidate for newborn screening (NBS). Our objective was to explore the use of a fluorometric assay that could be applicable for high-throughput analysis of IDS activity in dried blood spots (DBS). The median IDS activity in DBS samples from 1,426 newborns was 377 pmol/punch/17 h (range 78-1111). The IDS activity in one sample was repeatedly under the cutoff value (set at 20% of the median value), which would imply a recall rate of 0.07%. A sample from a clinically diagnosed MPS II individual, included in each 96-well test plate, had IDS activities well below the 20% cutoff value. Coefficients of variation in quality control samples with low, medium, and high IDS activities (190, 304, and 430 pmol/punch/17 h, respectively) were 12% to 16%. This small-scale pilot study shows that newborn screening for Hunter disease using a fluorometric assay in DBS is technically feasible with a fairly low recall rate. NBS may allow for identification of infants with Hunter disease before clinical symptoms become evident enabling early intervention.


Rictor/mTORC2 facilitates central regulation of energy and glucose homeostasis.
Insulin signaling in the central nervous system (CNS) regulates energy balance and peripheral glucose homeostasis. Rictor is a key regulatory/structural subunit of the mTORC2 complex and is required for hydrophobic motif site phosphorylation of Akt at serine 473. To examine the contribution of neuronal Rictor/mTORC2 signaling to CNS regulation of energy and glucose homeostasis, we utilized Cre-LoxP technology to generate mice lacking Rictor in all neurons, or in either POMC or AgRP expressing neurons. Rictor deletion in all neurons led to increased fat mass and adiposity, glucose intolerance and behavioral leptin resistance. Disrupting Rictor in POMC neurons also caused obesity and hyperphagia, fasting hyperglycemia and pronounced glucose intolerance. AgRP neuron specific deletion did not impact energy balance but led to mild glucose intolerance. Collectively, we show that Rictor/mTORC2 signaling, especially in POMC-expressing neurons, is important for central regulation of energy and glucose homeostasis.


Working together to address domestic violence among veterans.
Most veterans do not have psychiatric illness and do not have problems with domestic violence, but PTSD is a strong risk factor for intimate partner violence. Other risk factors include depression and substance use disorders, and the risk is compounded by the presence of several factors. Clinicians should screen for domestic violence among veterans and their partners using direct, nonjudgmental questions. To improve their relationships, veterans may need help with problems such as mistrust, low esteem for self or others, and power/control conflicts. Veterans and their intimate partners should also receive education about any psychiatric diagnosis that is given, the problem of survival-mode thinking at home, and available resources such as cognitive-behavioral interventions to prevent or stop domestic violence. When addressing a veteran's domestic violence, coordination of care is necessary to reduce recidivism. With intimate partners, clinicians should discuss the support system and safety plan.


Cancer Diagnosis, Treatment Linked to Suicide Risk.
Two recent studies pull data from millions of patient records to provide a comprehensive picture of cancer's psychologic burden on patients with different tumor types and treatment regimens. The findings underscore the elevated risk of suicide and self-harm among patients with cancer and can help oncologists identify those in need of psychiatric care.


The Therapeutic Effects of DDP/CD44-shRNA Nanoliposomes in AMF on Ovarian Cancer.
Globally, ovarian cancer is one of the most common gynecological malignant tumors, and the overall curative effect has been unsatisfactory for years. Exploring and investigating novel therapeutic strategy for ovarian cancer are an imperative need. Using manganese zinc ferrite nanoparticles (PEG-MZF-NPs) as gene transferring vector and drug delivery carrier, a new combinatorial regimen for the target treatment of ovarian cancer by integrating CD44-shRNA, DDP (cisplatin) and magnetic fluid hyperthermia (MFH) together was designed and investigated in vivo and in vitro in this study. PEG-MZF-NPs/DDP/CD44-shRNA nanoliposomes were successfully prepared, and TEM detection indicated that they were 15-20 nm in diameter, with good magnetothermal effect in AMF, similar to the previously prepared PEG-MZF-NPs. Under the action of AMF, PEG-MZF-NPs/shRNA/DDP nanoliposomes effectively inhibited ovarian tumors' growth, restrained the cancer cells' proliferation and invasion, and promoted cell apoptosis. VEGF, survivin, BCL-2, and BCL-xl proteins significantly decreased, while caspase-3 and caspase-9 proteins markedly increased both in vitro and in vivo, far better than any of the individual therapies did. Moreover, no significant effects were found on bone marrow hematopoiesis and liver and kidney function of nude mice intervened by the combinatorial therapeutic regimen. In the present study, we developed PEG-MZF-NPs/DDP/CD44-shRNA magnetic nanoliposomes and inaugurated an integrated therapy through the synergistic effect of MFH, gene therapy, and chemotherapy, and it shows a satisfactory therapeutic effect on ovarian cancer in vitro and in vivo, much better than any single treatment regimen did, with no significant side effects. This study provides a new promising method for ovarian cancer treatment.


Risk Factors Associated with Perinatal Relapse to Opioid Use Disorder.
The recent opioid epidemic in the United States has led to rising prevalence of maternal opioid use disorder (OUD). First-line treatment for maternal OUD involves the use of opioid agonist pharmacotherapy, such as methadone or buprenorphine, in addition to cognitive behavioral therapy and counseling. The management of maternal OUD can become overwhelming for both patients and clinicians, especially during the early postpartum period. Therefore, it is imperative that clinicians understand the impact of additional stressors in caring for these patients. Maternal chronic opioid dependence can lead to neonatal opioid withdrawal syndrome after birth. This multisystem condition affects neonatal neurobehavioral functioning and has significant human and socioeconomic consequences. First-line treatment for this syndrome involves intensive nonpharmacologic comforting measures, with maternal presence and involvement being central to ensuring the success of such measures. In this review, we describe the factors that place pregnant and postpartum women with OUD at risk of returning to illicit opioid use. We evaluate these multifaceted personal, social, societal, and systemic factors to inform the development of future clinical care initiatives.


Synthesis of new 3-methylthio-5-aryl-4-isothiazolecarbonitriles with broad antiviral spectrum.
The isothiazole derivative 3-methylthio-5-(4-OBn-phenyl)-4-isothiazolecarbonitrile, coded IS-50, which in previous studies had exhibited a broad antipicornavirus spectrum of action, was selected as the model for the synthesis of a new series of 3-methylthio-5-aryl-4-isothiazolecarbonitriles. These compounds were prepared in good yield (from 66 to 82%) by alkylation of 3-methylthio-5-(4-hydroxyphenyl)-4-isothiazolecarbonitrile with suitable bromides in the presence of acetone; only the 4-cyanophenoxy derivatives were obtained in a yield of less than 30%. All the compounds were screened against a panel of 17 representative human rhinovirus (HRV) serotypes belonging to both A and B groups, enteroviruses polio 1, ECHO 9 and Coxsackie B1, cardiovirus EMC, measles virus, and herpes simplex virus type 1 (HSV-1). Our results demonstrate that HRV 86 (group A) and HRVs 39 and 89 (group B) are the rhinovirus serotypes more susceptible to the action of these compounds. Isothiazole derivatives with a longer intermediate alkyl chain exhibited good activity against polio 1 and ECHO 9. The compound bearing a butyl group between the two phenoxy rings showed the lowest IC(50) against Coxsackie B1 and measles viruses. No activity against HSV-1 was detected with any of the compounds screened.


Inhibition of isoprenylcysteine carboxylmethyltransferase induces autophagic-dependent apoptosis and impairs tumor growth.
Inhibition of isoprenylcysteine carboxylmethyltransferase (Icmt), which catalyzes the final step in the post-translational C-terminal processing of prenylated proteins, suppresses tumor cell growth and induces cell death. Icmt inhibition by either a small molecule inhibitor termed as cysmethynil or inhibitory RNA induces marked autophagy leading to cell death. HepG2 cells were used to investigate the function of autophagy in tumor cell death. Suppression of autophagy, either pharmacologically or through knockdown of the autophagy essential proteins, Atg5 or Atg1, inhibits not only cysmethynil-induced autophagy, but also apoptosis in HepG2 cells. The dependence of cysmethynil-induced apoptosis on autophagy was further shown using autophagy-deficient mouse embryonic fibroblast (MEF) cells. Atg5(-/-) MEF cells were found to be resistant to cysmethynil-induced apoptosis, whereas wild-type MEFs showed high sensitivity to apoptosis induction. These data indicate that inhibition of Icmt can elicit cell death through two linked mechanisms, autophagy and apoptosis, and that autophagy can be an active player upstream of apoptosis in cell types capable of apoptotic cell death, such as HepG2 and MEFs. Further, treatment of mice-bearing HepG2-derived tumors with cysmethynil resulted in marked inhibition of tumor growth; analysis of tumor tissue from these mice revealed markers consistent with autophagy induction and cell growth arrest.


The Effect of Cytoreductive Partial Nephrectomy in Elderly Patients with Metastatic Renal Cell Carcinoma.
To explore the survival value of cytoreductive partial nephrectomy (cPN) in elderly with metastatic renal cell carcinoma (EmRCC) and evaluate the characteristics of patients who benefit from cPN. This was a study including 6105 patients aged ≥65 years with metastatic renal cell carcinoma (RCC) queried from Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2015, among which 1264 patients underwent cytoreductive nephrectomy (CN), 78 patients underwent cPN and 1186 patients underwent cytoreductive radical nephrectomy (cRN). Kaplan-Meier (K-M) method and Cox proportional-hazards model (COX) were used to evaluate the survival prognosis. Overall survival (OS) was compared between groups using propensity score matching (PSM) to balance the effects of confounding factors such as general features and pathological features. At last, we constructed a nomogram visualization modelled by R language to predict survival. For patients with EmRCC, especially for male patients with tumors size ≤7 cm, N0 stage, or isolated metastases, cPN brought a better survival than cRN. Tumor size and N stage were independent risk factors affecting the survival of cPN patients. cPN for patients with tumor size >7 cm or N1 stage may present a higher risk of death. The implementation of cPN for patients with EmRCC who meet specific clinical characteristics such as tumors size ≤7 cm, N0 stage, or isolated metastases seems to help improve the survival prognosis.


Purification and biochemical characterization of alkaline serine protease from Caesalpinia bonducella.
A high molecular weight serine protease has been purified to electrophoretic homogeneity from the seeds of Caesalpinia bonducella Flem. (Caesalpiniaceae) by the combination of size exclusion and ion exchange chromatography. About 524 fold purification was achieved with an overall recovery of 6.8%. The specific activity was found to be 86 U/mg/min at pH 8.0. The calculated K(m) and V(max) were 1.66 mg/mL and 496.68 units/min per mg of protein, respectively. The molecular mass was estimated to be about 63 kDa by sodium dodecyl sulfate PAGE. The enzyme showed optimum activity at pH 8.0 and exhibited its highest activity at 40 degrees C. The enzyme was strongly inhibited by 2mM phenylmethylsulfonyl fluoride (PMSF), suggesting the presence of a serine residue at the active site. PMSF showed a pure competitive type of inhibition with the serine protease enzyme. It was observed that enzyme activity was enhanced in the presence of dications and was active against a variety of modified substrates and natural proteins.


Dipyridamole decreases circulating renin-angiotensin system activity in hypertensive patients.
To study the effect of adenosine on renin release, n = 6 hypertensive patients, while on a constant 80 to 100 mEq/24 h Na+ diet, received oral 150 mg dipyridamole (an adenosine uptake inhibitor) three times daily for 3 days while upright plasma renin activity (PRA) and plasma aldosterone, urinary aldosterone, plasma and urinary Na+,K+, and creatinine clearance were monitored the day before (basal) the first and third day of the treatment and the day after the withdrawal (recovery). As compared to basal and to recovery, dipyridamole significantly decreased PRA, and plasma and urinary aldosterone without affecting plasma and urinary Na+ and K+, creatinine clearance, blood pressure, and heart rate. These data, showing that dipyridamole decreases PRA and aldosterone, confirm also in hypertensives that endogenous adenosine inhibits the circulating renin-angiotensin-aldosterone system.


Experimental test of social norms theory in a real-world drinking environment.
Social norms theory articulates that behavior is influenced by perceptions of behavioral norms. Social norms interventions attempt to modify perceptions of what behavior is normative as a means of influencing actual behavior. Social norms interventions have been widely used on college campuses to reduce the level of student drinking. The effectiveness of these interventions has been mixed. A social norms program might fail because the intervention operations failed to sufficiently implement social norms theory in the real world or because of the theory's limitations. Our research involves an experimental examination of the impact of social norms information on actual drinking behavior within a real-world drinking environment. Nearly 3,000 participants were interviewed and randomly assigned to one of nine social norms feedback conditions before heading to bars and nightclubs in Tijuana, Mexico. These same participants were resampled, interviewed again, and subjected to breath alcohol analysis when they returned to the United States. We found that persons whose perceptions of normative drinking changed (became more accurate) during their visit to Tijuana consumed relatively less alcohol. We also found that providing participants with social norms feedback produced more accurate perceived norms. However, the effect sizes were too small to produce statistically significant results showing that social norms feedback could effectively reduce drinking via changing normative perceptions. Our research demonstrated that providing social norms feedback changed perceived drinking norms and that changes in perceived norms were correlated with reduced drinking. Effect sizes, however, were quite small.


Cross-sex cecal microbiota transfer alters depressive-like behaviours in mice.
Major depressive disorder (MDD) is a leading cause of non-fatal global disease burden, with females being two-fold more likely than males to be diagnosed with the disorder. Despite this sex-linked disparity of diagnosis, it is unclear what underlies the sex bias in MDD. Recent findings suggest a role for the gut in mediating affective disorders through the gut-brain-axis (GBA). However, few studies have included sex as a biological variable. For this study, cross-sex transfer of cecal microbiota was performed between male and female C57Bl/6 mice to elucidate the effects of sex and the gut microbiome on a standard battery of tests measuring depressive-like behaviours. Specifically, regardless of sex, recipients of male cecal content had a greater sucrose preference than controls and recipients of female cecum, although recipients of male cecal transfer also showed a trend towards increased passive coping on the force swim test. Conversely, in the splash test, recipients of female cecum displayed a decrease in grooming behaviour compared to both controls and recipients of male cecum, suggestive of an increase in depressive-like behaviour. These results support a role for female-specific gut microbes in contributing to female vulnerability to depression, particularly on self-care measures, while male-specific gut microbes may protect in part against an anhedonia-like phenotype, but increase passive coping.


Lymphoma presenting as a periorbital tumor.
Lymphoma is a common tumor of the periorbital region. Facial radiographs may show a soft tissue mass. Radiologic differential diagnosis of orbital masses is difficult. Computed tomographic scanning with intravenous contrast medium is useful in diagnosing and staging neoplasms in this area.


Serotypes of Pseudomonas aeruginosa in clinical specimens in relation to antibiotic susceptibility.
Ninety-eight hospital strains of Pseudomonas aeruginosa isolated from six different hospitals in Athens were serotyped by a slide agglutination test with unabsorbed commercial antisera. Serotypes O6, O11, O12, and "pool E" strains (strains that agglutinated only in pool E, which contained antisera against O2, O5, O15, and O16 antigens, but did not agglutinate in the individual antisera) predominated, accounting for more than 62% of all isolates tested. In respect to serotypes, (i) there was no apparent correlation with hospital of origin, (ii) most strains of serotypes O6 and O11 were sensitive to gentamicin and carbenicillin (iii) most strains of pool E were from urine and were resistant to these drugs, (iv) all 9 strains of serotype O12 tested were resistant to carbenicillin and all 5 strains tested hydrolyzed this drug, and (v) 24 of 25 strains of pool E were resistant to carbenicillin but only 2 of 17 strains hydrolyzed it.


The pathology of primary IgA glomerulonephritis--a renal biopsy study.
Renal biopsies of 44 Chinese patients with primary IgA glomerulonephritis (IgA Gn) were examined by light (LM), electron (EM) and immunofluorescent microscopy (IF). The diagnosis of IgA Gn was based on IF staining showing predominant mesangial IgA deposition in the absence of systemic diseases. With LM, IgA Gn was not essentially different from other idiopathic forms of glomerulonephritis. The glomerular lesions showed features of focal proliferative glomerulonephritis (45.4%), focal sclerosing glomerulonephritis (25%), minimal glomerular lesions (18.2%) and diffuse mesangial proliferative glomerulonephritis (11.4%). Membranous and membrano-proliferative forms were not encountered. The variable LM findings contrasted markedly with the constancy of IF staining. EM revealed lumpy electron dense deposits in the mesangium in all cases which, in the relative absence of subendothelial and subepithelial deposits, might also be helpful in diagnosis.


Interaction of aluminum with paired helical filament tau is involved in neurofibrillary pathology of Alzheimer's disease.
Since the first reports of aluminum-induced neurofibrillary degeneration in experimental animals, extensive studies have been performed to clarify the role played by aluminum in the pathogenesis of Alzheimer's disease (AD). Additional evidence implicating aluminum in AD includes elevated levels of aluminum in the AD brain, epidemiologic data linking aluminum exposure to AD, and interactions between aluminum and protein components in the pathologic lesions of AD, i.e., neurofibrillary tangles (NFTs) and senile plaques. As most of this evidence is circumstantial and some of it is not consistent in all reports, the role of aluminum in the pathogenesis of AD has remained controversial. However, the interaction of aluminum with altered forms of tau in the paired helical filaments (PHFs) of neurofibrillary lesions is highly likely to contribute to the formation of NFTs because (1) aluminum and abnormally phosphorylated tau (known as PHF tau) are colocalized in NFTs, and (2) aluminum is known to preferentially interact with such phosphorylated proteins. Recently, it was demonstrated that aluminum binds selectively to PHF tau, induces PHF tau to aggregate, and retards the in vivo proteolysis of PHF tau. These data suggest that aluminum could serve as a cofactor in the formation of NFTs by interacting with PHF tau. This review summarizes the current understanding of how aluminum might contribute to the formation of neurofibrillary lesions from PHF tau in neurons of the AD brain.


Phosphorylation state of mu-opioid receptor determines the alternative recycling of receptor via Rab4 or Rab11 pathway.
Agonist-induced phosphorylation, internalization, and intracellular trafficking of G protein-coupled receptors are critical in regulating both cellular responsiveness and signal transduction. The current study investigated the role of receptor phosphorylation state in regulation of agonist-induced internalization and intracellular trafficking of mu-opioid receptor (MOR). Our results showed that after agonist stimulation, the recycle of a mutant MOR that lacks the C-terminal residues after Asn(362) (MOR362T) was greatly decreased, whereas a C-terminal phosphorylation sites-mutated MOR (MOR3A), which is deficient in agonist-induced phosphorylation recycled back to the membrane at a level comparable to that of the wild-type receptor, however, interestingly at a slower rate. Inhibition of functions of either Rab4 or Rab11 by dominant-negative mutants and small interfering RNA both significantly impaired the recycling of the wild-type MOR, whereas the recycling of the phosphorylation-deficient mutant was only inhibited by the dominant-negative mutant and small interfering RNA of Rab11, suggesting that the recycling of nonphosphorylated MOR is exclusively via Rab11-mediated pathway. Furthermore, phosphorylated MOR was observed accumulated in Rab5- and Rab4-, but not Rab11-positive vesicles. Our data indicate that both phosphorylated and nonphosphorylated MOR internalize via Rab5-dependent pathway after agonist stimulation, and the phosphorylated and nonphosphorylated MORs recycle through distinct vesicular trafficking pathways mediated by Rab4 and Rab11, respectively, which may ultimately lead to differential cellular responsiveness or downstream signaling.


Isolation, sequencing, and mutagenesis of the gene encoding cytochrome c553i of Paracoccus denitrificans and characterization of the mutant strain.
The periplasmically located cytochrome c553i of Paracoccus denitrificans was purified from cells grown aerobically on choline as the carbon source. The purified protein was digested with trypsin to obtain several protein fragments. The N-terminal regions of these fragments were sequenced. On the basis of one of these sequences, a mix of 17-mer oligonucleotides was synthesized. By using this mix as a probe, the structural gene encoding cytochrome c553i (cycB) was isolated. The nucleotide sequence of this gene was determined from a genomic bank. The N-terminal region of the deduced amino acid sequence showed characteristics of a signal sequence. Based on the deduced amino acid sequence of the mature protein, the calculated molecular weight is 22,427. The gene encoding cytochrome c553i was mutated by insertion of a kanamycin resistance gene. As a consequence of the mutation, cytochrome c553i was absent from the periplasmic protein fraction. The mutation in cycB resulted in a decreased maximum specific growth rate on methanol, while the molecular growth yield was not affected. Growth on methylamine or succinate was not affected at all. Upstream of cycB the 3' part of an open reading frame (ORF1) was identified. The deduced amino acid sequence of this part of ORF1 showed homology with methanol dehydrogenases from P. denitrificans and Methylobacterium extorquens AM1. In addition, it showed homology with other quinoproteins like alcohol dehydrogenase from Acetobacter aceti and glucose dehydrogenase from both Acinetobacter calcoaceticus and Escherichia coli. Immediately downstream from cycB, the 5' part of another open reading frame (ORF2) was found. The deduced amino acid sequence of this part of ORF2 showed homology with the moxJ gene products from P. denitrificans and M. extorquens AM1.


[Epidural anesthesia in surgical interventions on the spine and spinal cord. I. Comparative analysis of the effectiveness of anesthesiological protection under conditions of epidural anesthesia and neuroleptanalgesia in surgery of the spine and and spinal cord].
The study was carried out in 22 patients operated on for vertebral disk hernias and spinal tumors at lumbosacral level. The patients were divided in 2 groups depending on the type of anesthesia (epidural or neuroleptanalgesia-EA and NLA). In the test group all patients were operated under EA with local anesthetics combined with intravenous sedative drugs (diprivan + relanium) under conditions of spontaneous respiration and O2 inhalation through a mask. In the control group combined total intravenous anesthesia by myorelaxants and tracheal intubation were carried out (relanium + diprivan: induction dose 1.95 +/- 0.5 mg/kg, maintenance dose 5.3 +/- 0.4 mg/kg/h, and phentanyl). The purpose of the study was to compare the efficiency of anesthesiological protection under EA and traditional NLA in interventions on the spine, when surgical injury is inflicted in the immediate vicinity to the central structures responsible for pain impulsation. Only EA ensured adequate protection of the patients from surgical stress, as was seen from hemodynamic (arterial pressure and heart rate) and endocrine metabolic parameters (glucose, epinephrine, norepinephrine, hydrocortisone, and prolactin levels). Hence, EA fully demonstrated its protective properties during operations on the spine, and therefore can be regarded as a method of choice in this patient population.


Resynchronization of estrus in cattle of unknown pregnancy status using estrogen, progesterone, or both.
Our objective was to develop treatments applied to cattle of unknown pregnancy status that would resynchronize the repeat estrus of nonpregnant females. In Exp. 1, previously inseminated dairy and beef heifers were assigned randomly to each of three treatments 13 d after AI: 1) no treatment (controls; n = 44); 2) 0.5 mg of estradiol cypionate (ECP) i.m. on d 13 and 20 at the time of insertion and removal of a used intravaginal progesterone (P4)-releasing insert (CIDR; P4 + ECP; n = 44); and 3) same as P4 + ECP without injections of ECP (P4; n = 42). The P4 + ECP (>90%) and P4 (>75%) protocols effectively synchronized repeat periods of estrus to 2 d and did not harm established pregnancies. In Exp. 2, treatments similar to those in Exp. 1 were applied to previously inseminated beef heifers (n = 439). Feeding 0.5 mg of melengestrol acetate (MGA) from d 13 to 19 after AI replaced the CIDR as a source of progestin. Of those heifers not pregnant (n = 65) after the initial AI, more than 86% were reinseminated, but conception was decreased (P < 0.05) by 28 to 39% compared with controls. In Exp. 3, previously inseminated lactating beef cows at four locations were assigned within herd to each of three treatments: 1) no treatment (control; n = 307); 2) same as in Exp. 1, but with P4 + 1 mg of estradiol benzoate on d 13 and 20 (P4 + EB; n = 153); and 3) same as in Exp. 1, P4 + ECP (n = 149). Treatments with P4 plus estrogen did not decrease conception rates in pregnant cows at any location, but increased (P < 0.05) the percentage of nonpregnant cows returning to estrus between 19 and 23 d after timed AI from 29% in controls to 86% in P4 + EB and 65% in P4 + ECP cows. Conception rates at the return estrus were not decreased when treatments occurred between d 13 and 20. In Exp. 4, lactating beef cows were assigned as in Exp. 3 to each of three treatments: 1) no treatment (controls; n = 51); 2) P4 + ECP (n = 47), as in Exp. 1; and 3) a single injection of ECP on d 13 (n = 48). Previously established pregnancies were not harmed (P = 0.70), and return rates of nonpregnant cows did not differ (P = 0.78) among treatments. In summary, in both heifers and lactating beef cows, the P4-based resynchronization treatments increased synchronized return rates when estrus detection rates were low, had no negative effects on established pregnancies, and decreased or tended to decrease conception rates at the resynchronized estrus.


The role of alkalinity in setting water quality metrics: phosphorus standards in United Kingdom rivers.
UK implementation of the European Union Water Framework Directive (for the 2015-2021 cycle) Ecological Status (ES) classification for river phosphorus is based on the calculation of reference conditions for reactive phosphorus (RP) using river alkalinity measurements. Underpinning this approach is that the alkalinity is primarily from rock weathering and is free of anthropogenic influences. However, the potential contribution of anthropogenic alkalinity needs to be considered and, if possible, quantified. In the rural South West River Basin District of England, 38 river sites were examined with respect to river alkalinity loads in order to test this consideration. At river base flow when RP can cause enhanced algal growth, 9 sites (24%) had effluent alkalinity contributions amounting to 25-49% of the total riverine alkalinity load, while 11 (29%) of the sites received ≥50% of their alkalinity load from effluent. When flows increased above base flow to Q95 flow at these 11 sites, catchment diffuse run-off became the largest load of alkalinity at 9 of the sites, and that at the Q95 flows, combined effluent and diffuse alkalinity loads contributed 68-100% of the total alkalinity load. Anthropogenic alkalinity is likely to be present in diffuse run-off, but it is difficult to apportion alkalinity loads between natural and contaminant sources. It is likely that diffuse loads of alkalinity will dominate on the annual timescales used to assess WFD compliance, even at sites where ground water alkalinity dominates at base river flows. In principle, inclusion of anthropogenic alkalinity in the calculation of ES boundary concentrations for RP may lead to a relaxation of the standards. In practice this may not follow. It is likely that at the river sites used initially to develop the algorithms now used for P standard setting, anthropogenic alkalinity was present, to varying and unknown degrees, and that this alkalinity would have influenced the measured and reference RP and biological metrics on which the P standards are based. Apart from RP, alkalinity is also used to underpin water quality metrics for additional chemical and biological parameters, and for this reason, understanding the complex factors determining river alkalinity loads should be an important task for water quality regulators.


[Comparative study of diagnostic methods for visceral leishmaniasis in dogs from Ilha Solteira, SP].
The purpose of the present work was a comparative study of diagnostic methods for Canine Visceral Leishmaniasis (CVL) using serological methods, enzyme-linked immunosorbent assay (ELISA) and indirect fluorescent antibody test (IFAT), histochemical (HE) and immunohistochemical (IMHC) tests using spleen, lymph node and liver canine tissues. In addition, Polymerase Chain Reaction (PCR) was done in blood and in tissues in order to compare and confirm no conclusive and negative diagnosis by the methods above. For this study, 34 dogs were divided according to clinical signs in asymptomatic, oligosymptomatic and polisymptomatic Leishmania-infected dogs euthanized by Zoonotic Disease Control Center (CCZ) from Ilha Solteira, SP, Brazil. The positivism indexes of ELISA, IMHC, IFAT and HE were 65.0, 62.0, 56.0 and 56.0%, respectively with the highest numbers of positive dogs in polisymptomatic (92.0%) followed by oligosymptomatic (57.0%) and asymptomatic dogs (12.5%). Furthermore, PCR confirmed the positive results and detected DNA in tissues from 100% of negative dogs and 89.0% suspects raising the animal positivism index up to 97.0%. In conclusion, PCR was the most sensitive and a valuable method for a definitive CVL diagnosis.


Behind the Scenes: Endo/Exocytosis in the Acquisition of Metastatic Traits.
Alterations of endo/exocytic proteins have long been associated with malignant transformation, and genes encoding membrane trafficking proteins have been identified as bona fide drivers of tumorigenesis. Focusing on the mechanisms underlying the impact of endo/exocytic proteins in cancer, a scenario emerges in which altered trafficking routes/networks appear to be preferentially involved in the acquisition of prometastatic traits. This involvement in metastasis frequently occurs through the integration of programs leading to migratory/invasive phenotypes, survival and resistance to environmental stresses, epithelial-to-mesenchymal transition, and the emergence of cancer stem cells. These findings might have important implications in the clinical setting for the development of metastasis-specific drugs and for patient stratification to optimize the use of available therapies. Cancer Res; 77(8); 1813-7. ©2017 AACR.


[Japanese anatomical terminology (nomina anatomica japonica) from the educational view point (1)--sune and nezumi].
A few considerations on two Japanese anatomical terms, sune (the anterior part of the leg or the shin in medical terminology) and nezumi (the rat) from the anatomical point of view are made. Japanese words generally have two readings. For example, sune which means the anterior part of the leg, may be read as sune and kei. But kei has two other meanings, the neck and the road. Sune is used more for the anterior part of the leg than kei, especially in classes for beginners of the anatomical course. Nezumi means rat, but is also read as so. Because kei means road, and kan means canal, sokeikan means the rat's tubular passageway, namely, the descent of testis (Descensus testis). In Japanese anatomical terminology the passage of the testis through the inguinal canal is considered similar to a rat going through a passageway. The work sokeikan is better than the English anatomical term inguinal canal which means only the canal in the root of the groin. In Japanese, two words, fukurahagi and komura are used for the posterior part of the leg.


Using Electronic Clinical Decision Support to Examine Vision Rehabilitation Referrals and Practice Guidelines in Ophthalmology.
To examine ophthalmologist use of an electronic health record (EHR)-based clinical decision support system (CDSS) to facilitate low vision rehabilitation (LVR) care referral. The CDSS alert was designed to appear when best documented visual acuity was <20/40 or hemianopia or quadrantanopia diagnosis was identified during an ophthalmology encounter from November 6, 2017, to April 5, 2019. Fifteen ophthalmologists representing eight subspecialties from an academic medical center were required to respond to the referral recommendation (order, don't order). LVR referral rates and ophthalmologist user experience were assessed. Encounter characteristics associated with LVR referrals were explored using multilevel logistic regression analysis. The alert appeared for 3625 (8.9%) of 40,931 eligible encounters. The referral rate was 14.8% (535/3625). Of the 3413 encounters that met the visual acuity criterion only, patients who were worse than 20/60 were more likely to be referred, and 32.4% of referred patients were between 20/40 and 20/60. Primary reasons for deferring referrals included active medical or surgical treatment, refractive-related issues, and previous connection to LVR services. Eleven of the 13 ophthalmologists agreed that the alert was useful in identifying candidates for LVR services. A CDSS for patient identification and referral offers an acceptable mechanism to apply practice guidelines and prompt ophthalmologists to facilitate LVR care. Further study is warranted to optimize ophthalmologist user experience while refining alert criteria beyond visual acuity. The CDSS provides the framework for multi-center research to assess the development of pragmatic algorithms and standards for facilitating LVR care.


Noise sources in laser radar systems.
To understand the fundamental limit of performance with a given laser radar system, the phase noise of a testbed laser radar has been investigated. Apart from the phase noise in the transmitter laser and the local oscillator laser, additional phase noise was introduced by vibrations caused by fans in power supplies and cooling systems. The stability of the mechanical structure of the platform was also found to be of great importance. Furthermore, a model for the signal variations from diffuse targets has been developed. This model takes into account the stray light, the speckle decorrelation, and Doppler shift due to moving targets.


Effect of drug interactions involving antiretroviral drugs on viral load in HIV population.
Most studies focus on potential drug interactions, without considering the effect of these on the response to antiretroviral (ARV) therapy. We assess the effect of potential drug-drug interactions (pDDIs) that could have lowered the ARV concentration (pDDI-lowerARV) on HIV viral load. Retrospective observational cohort study was conducted on all HIV-infected outpatients attending the Pharmacy Service of a regional reference hospital in Murcia (south-eastern Spain). The complete treatment was subsequently screened for pDDIs using the database 'InteraccionesHIV.com'. The study focused on interactions involving at least one ARV drug and, especially, any pDDI-lowerARV. Two hundred and twenty-nine patients were included in the study. A total of 168 pDDIs were identified, of which 62 (36.9%) had the potential to lower ARV concentrations. In 77% of cases, the drug involved in the reduction of plasma concentrations was a protease inhibitor (PI), and in the rest of the drug interactions the ARV drug affected was a non-nucleoside reverse-transcriptase inhibitor. Baseline viral suppression was noted in 57.1% of patients with pDDI-lowerARV compared with 61.5% of patients without pDDI-lowerARV (p=0.605), and in 85.7% versus 79.7%, respectively, after a 24-week follow-up period (p=0.516). This study shows that prevalence of pDDI-lowerARV was high; however, no association was found between the presence of these interactions and virological failure. These results confirm the need for further studies to understand the consequences of interactions in real-life clinical practice, since most pharmacokinetic studies tend to evaluate the ability of interaction between two drugs under controlled conditions.


Fear of childbirth in late pregnancy.
A consecutive unselected series of 139 pregnant women were personally interviewed during their 31st--33rd week of gestation concerning their feelings at the prospect of the anticipated delivery. A severe fear of childbirth was admitted by 9 women (6%), and another 23 (17%) expressed a more moderate, but still distinct fear of delivery. Fear of physical pain was not found to be a dominant contributing factor, and an augmented service for obstetrical analgesia will, therefore, not suffice to curtail the problem of fear of childbirth. Instead, fear of childbirth, if present, must be promptly identified and correctly evaluated to be adequately treated.


Yersinia enterocolitica O:3 isolated from patients with or without reactive arthritis induces polyclonal activation of B cells and autoantibody production in vivo.
The mechanisms by which arthritis-provoking pathogens such as Yersinia enterocolitica interact with the human immune system to produce inflammatory synovitis are not well known. One of the immunomodulating mechanisms used against these pathogens is the polyclonal activation of lymphocytes. In this study, we investigated the extent of the B-lymphocyte activation induced in mice by a strain of Y. enterocolitica O:3 (FCF 526) isolated from a patient with arthritis, and compared it with two other strains, a virulent one (FCF 397[+]) isolated from a patient without arthritis and its plasmidless isogenic pair (FCF397[-]). Also we investigated the production of autoantibodies in mice infected with these different strains. SPF Swiss mice were infected intravenously with a suspension of Y. enterocolitica. Spleen cells were taken on days 7, 14, 21 and 28 after infection and the number of cells secreting nonspecific and specific antibodies of IgG1, IgG2a, IgG2b, IgG3, IgM and IgA isotypes were determined by the ELISPOT technique. The presence of autoantibodies in mouse serum was investigated by the dot-blot assay. The pattern of infection of the three bacterial strains were almost the same. We observed a general increase in the number of nonspecific Ig-secreting cells with all three strains, and the greatest increases observed were in the IgG2a and IgG3 isotypes. Only a small fraction of the immunoglobulins detected were antibacterial, suggesting that the rest resulted from polyclonal B cell activation. The strain isolated from the patient with arthritis (FCF526) induced the greatest production of autoantibodies, coinciding with the period in which the greatest activation of nonspecific B lymphocytes was seen. There were no signs of arthritis or inflammation in the joints of the infected animals. Based on our results, we were unable to determine whether there is an association between the arthritogenic capability of Y. enterocolitica and polyclonal activation of B cells.


Developing constraint in Bayesian mixed models.
Model comparison in Bayesian mixed models is becoming popular in psychological science. Here we develop a set of nested models that account for order restrictions across individuals in psychological tasks. An order-restricted model addresses the question "Does everybody," as in "Does everybody show the usual Stroop effect," or "Does everybody respond more quickly to intense noises than subtle ones?" The crux of the modeling is the instantiation of 10s or 100s of order restrictions simultaneously, one for each participant. To our knowledge, the problem is intractable in frequentist contexts but relatively straightforward in Bayesian ones. We develop a Bayes factor model-comparison strategy using Zellner and Siow's default g-priors appropriate for assessing whether effects obey equality and order restrictions. We apply the methodology to seven data sets from Stroop, Simon, and Eriksen interference tasks. Not too surprisingly, we find that everybody Stroops-that is, for all people congruent colors are truly named more quickly than incongruent ones. But, perhaps surprisingly, we find these order constraints are violated for some people in the Simon task, that is, for these people spatially incongruent responses occur truly more quickly than congruent ones! Implications of the modeling and conjectures about the task-related differences are discussed. (PsycINFO Database Record


Comprehensive Clinical Literature Review of Managing Bone Metastases in Breast Cancer: Focus on Pain and Skeletal-Related Events.
Bone metastases are the most common site of metastatic disease in breast cancer and can result in significant pain and an increased risk of skeletal-related events (SREs). Uncontrolled pain can further lead to negative outcomes. The aim is to provide oncology nurses with the latest evidence on the management of bone metastases in metastatic breast cancer (MBC) with a focus on pain and SREs. A literature search was conducted using the Embase®, PubMed®/MEDLINE®, CINAHL®, and Cochrane Library databases. Clinical trials, retrospective studies, systematic reviews, meta-analyses, and practice guidelines, as well as one high-level conference abstract, were reviewed. Options for managing bone metastases in MBC include surgical and interventional strategies, radiation, and bone-modifying agents. Management plans frequently include a combination of these modalities. More information is needed to better define the role of bone-directed therapies in MBC, particularly as they relate to nursing care.


Application of a beam homogenizer to planar laser diagnostics.
The first application of a microlens array beam homogenizer to planar laser measurement techniques in combustion diagnostics is demonstrated. The beam homogenizing properties of two microlens arrays in combination with a Fourier lens for widespread applications are presented. An uniform line profile with very little temporal fluctuations of the spatial intensity distribution was generated resulting in a significant reduction of measurement noise and enabling an easier and faster signal processing.


The neurocognitive signature of focus alternatives.
Focus alternatives are words/phrases that can substitute for the focused constituent of an utterance. In "Carsten has picked [CHERRIES]F from the tree.", (marked by pitch focus on cherries), the speaker wants to not only convey the fact that Carsten has picked cherries, but also to contrast cherries with other fruit that could have been picked, such as plums. Although focus alternatives are key to understanding the implicit aspects of an utterance, nothing is known about their neural representation. We directly contrasted neural representations of lexico-semantic similarity and focus alternative status using fMRI. Semantic relatedness was reflected in decreased activation in the bilateral superior temporal gyri. By contrast, processing of focus alternatives induced increased activations in the precuneus and the fronto-median wall, two regions previously implicated in discourse processing. These results suggest that focus alternative status is processed separately from semantic relatedness, at the level of discourse integration.


Burgeoning burden of non-communicable diseases in Nepal: a scoping review.
In the last decades, prevalence of non-communicable diseases (NCDs) has escalated in Nepal. This study reviews existing evidence on the burden of non-communicable diseases in Nepal using the framework developed by Arksey and O'Malley for scoping reviews. A total of 110 articles were identified from database searches, and four from additional searches. The titles and abstracts were reviewed using predetermined screening criteria. We limited our search to existing literature in English language and included all studies regardless of year of study. Both observational and interventional studies were included. Studies conducted outside Nepal and studies not reporting prevalence of NCDs were excluded. Additionally, we searched reference lists of included publications. All previous reports of Step Wise Surveillance to NCDs (STEPS Surveys) were included in the review. Finally, a total of 60 articles were included in this review. Limited studies on population-based prevalence of mental illness, chronic respiratory diseases, cardiovascular diseases, and road traffic accidents were found. There were limitations in the studies related to generalizability due to small sample sizes, non-random sampling and lack of studies from certain region of country. Nevertheless, high prevalence of hypertension and diabetes was found. Similarly, hospital-based studies reported high burden of cardiovascular diseases among outpatient contacts. Population-based cancer registries do not exist in Nepal. However, existing studies report 8,000-10,000 cancer deaths annually in Nepal. The most common cancer site in males was the lung, followed by the oral cavity and gastric, while the first three in females were cervix uteri, breast and lung. Prevalence of psychiatric morbidity was also high. Despite alarming burden of NCDs, the country's response is weak. Nepal needs to build non-communicable disease programmes with focus on disease prevention and management as well as awareness activities in urban and rural settings at community level.


Miro1 Regulates Neuronal Mitochondrial Transport and Distribution to Alleviate Neuronal Damage in Secondary Brain Injury After Intracerebral Hemorrhage in Rats.
Intracerebral hemorrhage (ICH) is a primary cause of death and disability in adults worldwide. Secondary brain injury (SBI) induced by ICH can lead to impaired mitochondrial function, which ultimately contributes to apoptosis and necrosis. Mitochondrial Rho GTPase 1 (Miro1) is a key regulator of mitochondrial movement and motor protein binding. Although Miro1 has been demonstrated to be implicated in various types of central nervous system damage, its potential effect on ICH-induced SBI has not been studied in detail. Hence, in the present new study, we explored the effect of Miro1 on SBI in vivo and in vitro. Self-body heart blood was injected into the right basal ganglia of the rat brain in vivo. Meanwhile, our in vitro model of ICH was based on the stimulation of oxygen hemoglobin (OxyHb) to neurons. Then, Miro1 was overexpressed both in the brains of rats after ICH in vivo and in OxyHb-treated cultured neurons in vitro. Miro1 overexpression in vivo reduced several pathological indexes such as brain edema, neurobehavioral impairment, and neuronal death. Immunofluorescent staining in vitro showed that overexpression of Miro1 ameliorated neuronal damage via facilitation of mitochondrial transport and distribution. JC-1 staining indicated that overexpression of Miro1 reduced the collapse of mitochondrial membrane potential and enhanced mitochondrial mass. Additionally, live-dead cellular staining and flow cytometry analysis revealed that Miro1 overexpression in cultured neurons reduced both necrotic and apoptotic rates. In contrast, inhibition of Miro1 expression yielded opposite effects to those of Miro1 overexpression. Above all, the upregulation of Miro1 significantly alleviated pathological symptoms on SBI in vivo and in vitro.


[Characteristics of the sympathoadrenal system response to psychoemotional stress under hypoxic conditions in aged people with physiological and accelerated aging of the respiratory system].
The peculiarities of the response of the sympathoadrenal system to psychoemotional and hypoxic stress in healthy young people and in aged people with physiological and accelerated aging of respiratory system were studied. It was shown that in aging a more pronounced response of the sympathoadrenal system to psychoemotional stress. At the same time, elderly people with different types of aging of the respiratory system did not demonstrate a difference in the response of the sympathoadrenal system to psychoemotional stress. Unlike in young people, in aged people, combination of psychoemotional and hypoxic stresses resulted in further activation of the sympathoadrenal system. The reaction of the sympathoadrenal system was more expressed in elderly people with accelerated ageing of the respiratory system.


Although calnexin is essential in S. pombe, its highly conserved central domain is dispensable for viability.
In mammalian cells, the calnexin/calreticulin chaperones play a key role in glycoprotein folding and its control within the endoplasmic reticulum (ER), by interacting with folding intermediates via their monoglucosylated glycans. This lectin activity has been mapped in mammalian calnexin/calreticulin chaperones to the central region, which is a highly conserved feature of calnexin/calreticulin molecules across species. The central domain has also been implicated in Ca(2+) binding, and it has been proposed to be involved in the regulation of calcium homeostasis in the ER. Herein, we show that although the Schizosaccharomyces pombe calnexin is essential for viability, cells lacking its 317-amino-acid highly conserved central region are viable under normal growth conditions. However, the central region appears to be necessary for optimal growth under high ER-stress, suggesting that this region is important under extreme folding situations (such as DTT and temperature). The minimal length of calnexin required for viability spans the C-terminal 123 residues. Furthermore, cells with the central domain of the protein deleted were affected in their morphology at 37 degrees C, probably due to a defect in cell wall synthesis, although these mutant cells exhibited the same calcium tolerance as wild-type cells at 30 degrees C.


Antitumor platinum(IV) derivatives of oxaliplatin with axial valproato ligands.
We report new anticancer prodrugs, platinum(IV) derivatives of oxaliplatin conjugated with valproic acid (VPA), a well-known drug having histone deacetylase inhibitory activity. Like most platinum(IV) derivatives, the cytotoxicity of the conjugates was lower in cell culture than that of oxaliplatin, but greater than those of its Pt(IV) derivative containing biologically inactive axial ligands in several cancer cell lines. Notably, these conjugates display activity in both cisplatin sensitive- and resistant tumor cells capable of both markedly enhanced accumulation in tumor cells and acting in a dual threat manner, concurrently targeting histone deacetylase and genomic DNA. These results demonstrate the dual targeting strategy to be a valuable route to pursue in the design of platinum agents which may be more effective in cancer types that are typically resistant to therapy by conventional cisplatin. Moreover, platinum(IV) derivatives containing VPA axial ligands seem to be promising dual-targeting candidates for additional preclinical studies.


Development of posterior hypothalamic neurons enlightens a switch in the prosencephalic basic plan.
In rats and mice, ascending and descending axons from neurons producing melanin-concentrating hormone (MCH) reach the cerebral cortex and spinal cord. However, these ascending and descending projections originate from distinct sub-populations expressing or not "Cocaine-and-Amphetamine-Regulated-Transcript" (CART) peptide. Using a BrdU approach, MCH cell bodies are among the very first generated in the hypothalamus, within a longitudinal cell cord made of earliest delaminating neuroblasts in the diencephalon and extending from the chiasmatic region to the ventral midbrain. This region also specifically expresses the regulatory genes Sonic hedgehog (Shh) and Nkx2.2. First MCH axons run through the tractus postopticus (tpoc) which gathers pioneer axons from the cell cord and courses parallel to the Shh/Nkx2.2 expression domain. Subsequently generated MCH neurons and ascending MCH axons differentiate while neurogenesis and mantle layer differentiation are generalized in the prosencephalon, including telencephalon. Ascending MCH axons follow dopaminergic axons of the mesotelencephalic tract, both being an initial component of the medial forebrain bundle (mfb). Netrin1 and Slit2 proteins that are involved in the establishment of the tpoc and mfb, respectively attract or repulse MCH axons.We conclude that first generated MCH neurons develop in a diencephalic segment of a longitudinal Shh/Nkx2.2 domain. This region can be seen as a prosencephalic segment of a medial neurogenic column extending from the chiasmatic region through the ventral neural tube. However, as the telencephalon expends, it exerts a trophic action and the mfb expands, inducing a switch in the longitudinal axial organization of the prosencephalon.


Mapping the Carbon Footprint of Nations.
Life cycle thinking asks companies and consumers to take responsibility for emissions along their entire supply chain. As the world economy becomes more complex it is increasingly difficult to connect consumers and other downstream users to the origins of their greenhouse gas (GHG) emissions. Given the important role of subnational entities-cities, states, and companies-in GHG abatement efforts, it would be advantageous to better link downstream users to facilities and regulators who control primary emissions. We present a new spatially explicit carbon footprint method for establishing such connections. We find that for most developed countries the carbon footprint has diluted and spread: for example, since 1970 the U.S. carbon footprint has grown 23% territorially, and 38% in consumption-based terms, but nearly 200% in spatial extent (i.e., the minimum area needed to contain 90% of emissions). The rapidly growing carbon footprints of China and India, however, do not show such a spatial expansion of their consumption footprints in spite of their increasing participation in the world economy. In their case, urbanization concentrates domestic pollution and this offsets the increasing importance of imports.


New chromosome-scale genomes provide insights into marine adaptations of sea snakes (Hydrophis: Elapidae).
Sea snakes underwent a complete transition from land to sea within the last ~ 15 million years, yet they remain a conspicuous gap in molecular studies of marine adaptation in vertebrates. Here, we generate four new annotated sea snake genomes, three of these at chromosome-scale (Hydrophis major, H. ornatus and H. curtus), and perform detailed comparative genomic analyses of sea snakes and their closest terrestrial relatives. Phylogenomic analyses highlight the possibility of near-simultaneous speciation at the root of Hydrophis, and synteny maps show intra-chromosomal variations that will be important targets for future adaptation and speciation genomic studies of this system. We then used a strict screen for positive selection in sea snakes (against a background of seven terrestrial snake genomes) to identify genes over-represented in hypoxia adaptation, sensory perception, immune response and morphological development. We provide the best reference genomes currently available for the prolific and medically important elapid snake radiation. Our analyses highlight the phylogenetic complexity and conserved genome structure within Hydrophis. Positively selected marine-associated genes provide promising candidates for future, functional studies linking genetic signatures to the marine phenotypes of sea snakes and other vertebrates.


Spatial covariation of competing species in a fluctuating environment.
Understanding how stochastic fluctuations in the environment influence population dynamics is crucial for sustainable management of biological diversity. However, because species do not live in isolation, this requires knowledge of how species interactions influence population dynamics. In addition, spatial processes play an important role in shaping population dynamics. It is therefore important to improve our understanding of how these different factors act together to shape patterns of abundance across space within and among species. Here, we present a new analytical model for understanding patterns of covariation in space between interacting species in a stochastic environment. We show that the correlation between two species in how they experience the same environmental conditions determines how correlated fluctuations in their densities would be in the absence of competition. In other words, without competition, synchrony between the species is driven by the environment, similar to the Moran effect within a species. Competition between the two species causes their abundances to become less positively or more negatively correlated. The same strength of competition has a greater negative effect on the correlation between species when one of them has a more variable growth rate than the other. In addition, dispersal or other movement weakens the effect of competition on the interspecific correlation. Finally, we show that movement increases the distance over which the species are (positively or negatively) correlated, an effect that is stronger when the species are competitors, and that there is a close connection between the spatial scaling of population synchrony within a species and between species. Our results show that the relationships between the different factors influencing interspecific correlations in abundance are not simple linear ones, but this model allows us to disentangle them and predict how they will affect population fluctuations in different situations.


Burnout syndrome and depression in students of a Colombian medical school, 2018.
Burnout syndrome (BS) has been evaluated in few populations of medical students, and its relationship with depression is even less studied. The objective was to determine the frequency of BS in medical students of the Universidad Pedagógica y Tecnológica de Colombia (UPTC), in Tunja, Colombia, as well as its association with depression and other social, economic, demographic, and academic factors. An observational, analytical, cross-sectional study was carried out on 182 UPTC medical students during 2018. The Maslach Burnout Inventory-Student Survey (MBI-SS) was applied, with which 3 components were obtained to determine positive SB. This was crossed in the Stata 15 program for depression and other social, economic, demographic, and academic covariates with the Generalised Linear Model (GLM). Of 182 respondents, 51.4% were women. The median age was 21 years (20-23 years). 14% had BS, of which 48% had depression. In the multiple regression, BS was significantly associated with a higher frequency of depression (RPa = 5.54; IC95%, 2.36-13.02; P < 0.001) and the feeling of insufficient money (RPa = 4.37; IC95%, 1.95-9.83; P < 0.001), in contrast to a negative association with smoking (RPa = 0.13; IC95%, 0.06-0.30; P < 0.001) and being a woman (RPa = 0.32; IC95%, 0.12-0.82; P = 0.018). The age of onset of marijuana use was not significant. BS shows a high association with increased depression and a feeling that the money is not enough at the end of the month, but it showed a negative association with tobacco consumption and being a woman. Such students should be detected to provide them with adequate academic support.


Deletions in the genomes of pseudorabies virus vaccine strains and existence of four isomers of the genomes.
As part of a study designed to identify the genes responsible for the virulence of pseudorabies virus, we have mapped the genomes of two independently derived vaccine strains (Bartha and Norden) by restriction enzyme analysis. The structures of these genomes have been compared with that of the genome of a laboratory strain previously mapped, of restriction fragments which had been cloned. The genome of the Bartha strain was found to be very similar to that of other pseudorabies virus strains, except that a deletion of approximately 2.7 X 10(6) daltons was found in the unique short (US) region. This deletion was also observed in the genome of the Norden vaccine strain but was not observed in the genomes of any other pseudorabies virus strains that have been studied (more than 20). The genome of the Norden strain differs from that of other pseudorabies virus strains in several other respects as well. The most important difference is that in contrast to all other pseudorabies virus strains analyzed to date, which contain a type 2 herpesvirus DNA molecule (in which the US region only inverts itself relative to the unique long [UL] region), the genome of the Norden strain is a type 3 molecule in which both the US and the UL regions of the genome invert themselves, giving rise to four isomeric forms of the genome. The ability of the UL region to invert itself is probably related to the fact that a sequence normally present in all other pseudorabies virus strains at the end of the UL only is found also in inverted form at the junction of the UL and the internal inverted repeat in the Norden strain.


Application of 1H Nuclear Magnetic Resonance Spectroscopy as Spirit Drinks Screener for Quality and Authenticity Control.
Due to legal regulations, the rise of globalised (online) commerce and the need for public health protection, the analysis of spirit drinks (alcoholic beverages >15% vol) is a task with growing importance for governmental and commercial laboratories. In this article a newly developed method using nuclear magnetic resonance (NMR) spectroscopy for the simultaneous determination of 15 substances relevant to assessing the quality and authenticity of spirit drinks is described. The new method starts with a simple and rapid sample preparation and does not need an internal standard. For each sample, a group of 1H-NMR spectra is recorded, among them a two-dimensional spectrum for analyte identification and one-dimensional spectra with suppression of solvent signals for quantification. Using the Pulse Length Based Concentration Determination (PULCON) method, concentrations are calculated from curve fits of the characteristic signals for each analyte. The optimisation of the spectra, their evaluation and the transfer of the results are done fully automatically. Glucose, fructose, sucrose, acetic acid, citric acid, formic acid, ethyl acetate, ethyl lactate, acetaldehyde, methanol, n-propanol, isobutanol, isopentanol, 2-phenylethanol and 5-(hydroxymethyl)furfural (HMF) can be quantified with an overall accuracy better than 8%. This new NMR-based targeted quantification method enables the simultaneous and efficient quantification of relevant spirit drinks ingredients in their typical concentration ranges in one process with good accuracy. It has proven to be a reliable method for all kinds of spirit drinks in routine food control.


Noncontact holographic detection for photoacoustic tomography.
A holographic method for high-speed, noncontact photoacoustic tomography is introduced and evaluated. Relative changes of the object's topography, induced by the impact of thermoelastic pressure waves, were determined at nanometer sensitivity without physical contact. The object's surface was illuminated with nanosecond laser pulses and imaged with a high-speed CMOS camera. From two interferograms measured before and after excitation of the acoustic wave, surface displacement was calculated and then used as the basis for a tomographic reconstruction of the initial pressure caused by optical absorption. The holographic detection scheme enables variable sampling rates of the photoacoustic signal of up to 50 MHz. The total acquisition times for complete volumes with 230 MVoxel is far below 1 s. Measurements of silicone and porcine skin tissue phantoms with embedded artificial absorbers, which served as a model for human subcutaneous vascular networks, were possible. Three-dimensional reconstructions of the absorbing structures show details with a diameter of 310 μm up to a depth of 2.5 mm. Theoretical limitations and the experimental sensitivity, as well as the potential for in vivo imaging depending on the detection repetition rate, are analyzed and discussed.


Irving John Selikoff and the strange case of the missing medical degrees.
Between the early 1960s and his death, Irving John Selikoff (1915-1992) was the dominant figure in the field of asbestos and health. He was particularly important in helping to establish a causal association between relatively low and spasmodic exposure to asbestos dust on the part of insulation workers and excess mortality rates. Through scientific and other activities, he played as large a part as anyone in destroying the American asbestos industry. This article traces Selikoff's medical education across three continents between 1936 and 1945. This education was relatively brief, patchy, and in some respects substandard. Selikoff never obtained the M.D. degree he repeatedly claimed he possessed. Questions are raised about how he attained such high professional recognition given his very modest educational attainments. Reflections are offered about whether asbestos regulation and litigation might have been different if Selikoff's evasions had come to light before now.


Precision medicine in gastric cancer.
Gastric cancer (GC) is a complex disease linked to a series of environmental factors and unhealthy lifestyle habits, and especially to genetic alterations. GC represents the second leading cause of cancer-related deaths worldwide. Its onset is subtle, and the majority of patients are diagnosed once the cancer is already advanced. In recent years, there have been innovations in the management of advanced GC including the introduction of new classifications based on its molecular characteristics. Thanks to new technologies such as next-generation sequencing and microarray, the Cancer Genome Atlas and Asian Cancer Research Group classifications have also paved the way for precision medicine in GC, making it possible to integrate diagnostic and therapeutic methods. Among the objectives of the subdivision of GC into subtypes is to select patients in whom molecular targeted drugs can achieve the best results; many lines of research have been initiated to this end. After phase III clinical trials, trastuzumab, anti-Erb-B2 receptor tyrosine kinase 2 (commonly known as ERBB2) and ramucirumab, anti-vascular endothelial growth factor receptor 2 (commonly known as VEGFR2) monoclonal antibodies, were approved and introduced into first- and second-line therapies for patients with advanced/metastatic GC. However, the heterogeneity of this neoplasia makes the practical application of such approaches difficult. Unfortunately, scientific progress has not been matched by progress in clinical practice in terms of significant improvements in prognosis. Survival continues to be low in contrast to the reduction in deaths from many common cancers such as colorectal, lung, breast, and prostate cancers. Although several target molecules have been identified on which targeted drugs can act and novel products have been introduced into experimental therapeutic protocols, the overall approach to treating advanced stage GC has not substantially changed. Currently, surgical resection with adjuvant or neoadjuvant radiotherapy and chemotherapy are the most effective treatments for this disease. Future research should not underestimate the heterogeneity of GC when developing diagnostic and therapeutic strategies aimed toward improving patient survival.


Astrophysical observations: lensing and eclipsing Einstein's theories.
Albert Einstein postulated the equivalence of energy and mass, developed the theory of special relativity, explained the photoelectric effect, and described Brownian motion in five papers, all published in 1905, 100 years ago. With these papers, Einstein provided the framework for understanding modern astrophysical phenomena. Conversely, astrophysical observations provide one of the most effective means for testing Einstein's theories. Here, I review astrophysical advances precipitated by Einstein's insights, including gravitational redshifts, gravitational lensing, gravitational waves, the Lense-Thirring effect, and modern cosmology. A complete understanding of cosmology, from the earliest moments to the ultimate fate of the universe, will require developments in physics beyond Einstein, to a unified theory of gravity and quantum physics.


RYF-Net: Deep Fusion Network for Single Image Haze Removal.
Haze removal from a single image is a challenging task. Estimation of accurate scene transmission map (TrMap) is the key to reconstruct the haze-free scene. In this paper, we propose a convolutional neural network based architecture to estimate the TrMap of the hazy scene. The proposed network takes the hazy image as an input and extracts the haze relevant features using proposed RNet and YNet through RGB and YCbCr color spaces respectively and generates two TrMaps. Further, we propose a novel TrMap fusion network (FNet) to integrate two TrMaPs and estimate robust TrMap for the hazy scene. To analyze the robustness of FNet, we tested it on combinations of TrMaps obtained from existing state-of-the-art methods. Performance evaluation of the proposed approach has been carried out using the structural similarity index, mean square error and peak signal to noise ratio. We conduct experiments on five datasets namely: D-HAZY ancuti2016d, Imagenet deng2009imagenet, Indoor SOTS li2017reside, HazeRD zhang2017hazerd and set of real-world hazy images. Performance analysis shows that the proposed approach outperforms the existing state-of-the-art methods for single image dehazing. Further, we extended our work to address high-level vision task such as object detection in hazy scenes. It is observed that there is a significant improvement in accurate object detection in hazy scenes using proposed approach.


Simultaneous removal of N and P in a SBR with production of valuable compounds: application to concentrated wastewaters.
This article examines the optimisation of recovery of phosphorus and nitrogen (via struvite) in small treatment units for high strength wastewaters using biologically assisted precipitation. The particular focus was the synergetic effect between removal of orthophosphate and the biological reactions occurring during nitrogen removal. The most sensitive parameter influencing the phosphate solid forms (HAP, MAP) is pH. Sequencing batch mode helps maintain high gradients in ammonia concentration, which encourages struvite precipitation. Nitrification has a key effect on the precipitation, through its influence on pH and ammonia concentration, determining the remaining soluble phosphorus concentration. Denitrification and CO(2) stripping, by increasing pH also improve precipitation of phosphorus. Optimal operating conditions will therefore depend on the chosen strategy: thus nitrification may help to keep phosphorus in a soluble form (as needed in direct urine reuse), whereas if co-precipitation is desired in the biological reactor, nitrification should be controlled in relation with others processes responsible for pH increase.


[Successful portal vein stent placement for chronic portal vein stenosis 5 years after pancreatoduodenectomy:a case report].
A 73-year-old man underwent pancreatoduodenectomy 5 years previously, and portal vein stenosis was observed immediately after surgery. A collateral vein with varices around the hepaticojejunostomy gradually developed. The patient experienced repeated episodes of melena that required transfusion. Enteroscopy confirmed varices around the hepaticojejunostomy, caused by portal vein stenosis, which was the source of intestinal bleeding. Varices were treated by placing an expandable metallic stent in the stenotic portal vein through a percutaneous transhepatic route. Although the portal vein stenosis was severe, the guidewire was successfully maneuvered into the superior mesenteric vein and stent placement was successful. Subsequently, the collateral vein disappeared and no further melena was observed.


Pressure-based alkaline lysis with immunocapture, a method for enhanced recovery in differential extraction.
A pressure-based protocol for differential extraction has been optimized to provide a rapid and selective alternative to conventional differential extraction techniques with the advantage of an increased recovery of genomic DNA. The protocol involves treating cotton swabs containing mixtures of sperm and vaginal epithelial cells with two sets of pressure treatment using a Barocycler® NEP 2320 in alkaline conditions. This first step quantitatively and selectively removes female epithelial cells. The cotton swab is removed and further treated with alkali at 95°C for the removal of sperm cell DNA. The resultant solution provides a clean male profile at a 20:1 cell ratio. Furthermore, the inclusion of a pretreatment step involving immunomagnetic cell capture of the female cells, permits nearly complete isolation of male sperm cells at cell ratios of up to 200:1 female to male cells.


Simultaneous visualization of the subfemtomolar expression of microRNA and microRNA target gene using HILO microscopy.
The family of microRNAs (miRNAs) not only plays an important role in gene regulation but is also useful for the diagnosis of diseases. A reliable method with high sensitivity may allow researchers to detect slight fluctuations in ultra-trace amounts of miRNA. In this study, we propose a sensitive imaging method for the direct probing of miR-10b (miR-10b-3p, also called miR-10b*) and its target (HOXD10 mRNA) in fixed cells based on the specific recognition of molecular beacons combined with highly inclined and laminated optical sheet (HILO) fluorescence microscopy. The designed dye-quencher-labelled molecular beacons offer excellent efficiencies of fluorescence resonance energy transfer that allow us to detect miRNA and the target mRNA simultaneously in hepatocellular carcinoma cells using HILO fluorescence microscopy. Not only can the basal trace amount of miRNA be observed in each individual cell, but the obtained images also indicate that this method is useful for monitoring the fluctuations in ultra-trace amounts of miRNA when the cells are transfected with a miRNA precursor or a miRNA inhibitor (anti-miR). Furthermore, a reasonable causal relation between the miR-10b and HOXD10 expression levels was observed in miR-10b* precursor-transfected cells and miR-10b* inhibitor-transfected cells. The trends of the miRNA alterations obtained using HILO microscopy completely matched the RT-qPCR data and showed remarkable reproducibility (the coefficient of variation [CV] = 0.86%) and sensitivity (<1.0 fM). This proposed imaging method appears to be useful for the simultaneous visualisation of ultra-trace amounts of miRNA and target mRNA and excludes the procedures for RNA extraction and amplification. Therefore, the visualisation of miRNA and the target mRNA should facilitate the exploration of the functions of ultra-trace amounts of miRNA in fixed cells in biological studies and may serve as a powerful tool for diagnoses based on circulating cancer cells.


Three phases of disaster relief in Haiti--pediatric surgical care on board the United States Naval Ship Comfort.
On January 12, 2010, Haiti experienced the western hemisphere's worst-ever natural disaster. Within 24 hours, the United States Naval Ship Comfort received orders to respond, and a group of more than 500 physicians, nurses, and staff undertook the largest and most rapid triage and treatment since the inception of hospital ships. These data represent pediatric surgical patients treated aboard the United States Naval Ship Comfort between January 19 and February 27, 2010. Prospective databases managed by patient administration, radiology, blood bank, laboratory services, and surgical services were combined to create an overall patient care database that was retrospectively reviewed for this analysis. Two hundred thirty-seven pediatric surgical patients were treated, representing 27% of the total patient population. These patients underwent a total of 213 operations composed of 243 unique procedures. Orthopedic procedures represented 71% of the total caseload. Patients returned to the operating room up to 11 times and required up to 28 days for completion of surgical management. This represents the largest cohort of pediatric surgical patients in an earthquake response. Our analysis provides a model for anticipating surgical caseload, injury patterns, and duration of surgical course in preparing for future disaster response missions. Moreover, we propose a 3-phased response to disaster medicine that has not been previously described.


The study of trypanosome species circulating in domestic animals in two human African trypanosomiasis foci of Côte d'Ivoire identifies pigs and cattle as potential reservoirs of Trypanosoma brucei gambiense.
Important control efforts have led to a significant reduction of the prevalence of human African trypanosomiasis (HAT) in Côte d'Ivoire, but the disease is still present in several foci. The existence of an animal reservoir of Trypanosoma brucei gambiense may explain disease persistence in these foci where animal breeding is an important source of income but where the prevalence of animal African trypanosomiasis (AAT) is unknown. The aim of this study was to identify the trypanosome species circulating in domestic animals in both Bonon and Sinfra HAT endemic foci. 552 domestic animals (goats, pigs, cattle and sheep) were included. Blood samples were tested for trypanosomes by microscopic observation, species-specific PCR for T. brucei sl, T. congolense, T. vivax and subspecies-specific PCR for T. b. gambiense and T. b. gambiense immune trypanolysis (TL). Infection rates varied significantly between animal species and were by far the highest in pigs (30%). T. brucei s.l was the most prevalent trypanosome species (13.7%) followed by T. congolense. No T. b. gambiense was identified by PCR while high TL positivity rates were observed using T. b. gambiense specific variants (up to 27.6% for pigs in the Bonon focus). This study shows that domestic animals are highly infected by trypanosomes in the studied foci. This was particularly true for pigs, possibly due to a higher exposure of these animals to tsetse flies. Whereas T. brucei s.l. was the most prevalent species, discordant results were obtained between PCR and TL regarding T. b. gambiense identification. It is therefore crucial to develop better tools to study the epidemiological role of potential animal reservoir for T. b. gambiense. Our study illustrates the importance of "one health" approaches to reach HAT elimination and contribute to AAT control in the studied foci.


[Cognitive alterations associated with HIV-1 infection and AIDS].
Primary neurological complications of AIDS include cognitive deficits such as HIV-associated dementia and milder forms such as cognitive/motor disorders, which cause changes in daily activities and reduce the quality of life of patients. Infection with HIV-1 is the most common, predictable and treatable cause of cognitive deficits in individuals with less than 50 years of age. Despite advances in the understanding of clinical characteristics, pathogenesis and neurobiological aspects and widespread use of highly active antiretroviral therapy (HAART), neurological complications and cognitive deficits still persist with serious personal and socioeconomic consequences, thus representing a great therapeutic challenge. In the pre-HAART era dementia was a common complication of infection whose incidence declined during the HAART era. However, prevalence of dementia has increased, especially that of milder forms due to the increased number of infected individuals and increased life expectancy. Cognitive alterations associated with HIV are typically sub cortical and can be associated with behavioral and motor disorders. These syndromes are clinically diagnosed by neuropsychological tests, while neuroimaging and analysis of cerebrospinal fluid contribute to diagnosis. This review is an update on current epidemiological status, clinical characteristics and diagnosis of cognitive complications observed during the course of HIV infection.


Receptor-mediated control of regulatory volume decrease (RVD) and apoptotic volume decrease (AVD).
A fundamental property of animal cells is the ability to regulate their own cell volume. Even under hypotonic stress imposed by either decreased extracellular or increased intracellular osmolarity, the cells can re-adjust their volume after transient osmotic swelling by a mechanism known as regulatory volume decrease (RVD). In most cell types, RVD is accomplished mainly by KCl efflux induced by parallel activation of K+ and Cl- channels. We have studied the molecular mechanism of RVD in a human epithelial cell line (Intestine 407). Osmotic swelling results in a significant increase in the cytosolic Ca2+ concentration and thereby activates intermediate-conductance Ca2+-dependent K+ (IK) channels. Osmotic swelling also induces ATP release from the cells to the extracellular compartment. Released ATP stimulates purinergic ATP (P2Y2) receptors, thereby inducing phospholipase C-mediated Ca2+ mobilization. Thus, RVD is facilitated by stimulation of P2Y2 receptors due to augmentation of IK channels. In contrast, stimulation of another G protein-coupled Ca2+-sensing receptor (CaR) enhances the activity of volume-sensitive outwardly rectifying Cl- channels, thereby facilitating RVD. Therefore, it is possible that Ca2+ efflux stimulated by swelling-induced and P2Y2 receptor-mediated intracellular Ca2+ mobilization activates the CaR, thereby secondarily upregulating the volume-regulatory Cl- conductance. On the other hand, the initial process towards apoptotic cell death is coupled to normotonic cell shrinkage, called apoptotic volume decrease (AVD). Stimulation of death receptors, such as TNF receptor and Fas, induces AVD and thereafter biochemical apoptotic events in human lymphoid (U937), human epithelial (HeLa), mouse neuroblastoma x rat glioma hybrid (NG108-15) and rat phaeochromocytoma (PC12) cells. In those cells exhibiting AVD, facilitation of RVD is always observed. Both AVD induction and RVD facilitation as well as succeeding apoptotic events can be abolished by prior treatment with a blocker of volume-regulatory K+ or Cl- channels, suggesting that AVD is caused by normotonic activation of ion channels that are normally involved in RVD under hypotonic conditions. Therefore, it is likely that G protein-coupled receptors involved in RVD regulation and death receptors triggering AVD may share common downstream signals which should give us key clues to the detailed mechanisms of volume regulation and survival of animal cells. In this Topical Review, we look at the physiological ionic mechanisms of cell volume regulation and cell death-associated volume changes from the facet of receptor-mediated cellular processes.


Quantum Materials Discovery by Combining Chemical and Physical Design Principles.
Exploratory quantum materials discovery remains crucial to progress in material science. Due to the grand challenges that we are facing in predicting these materials and their properties from scratch, chemical design principles remain a key ingredient for the discovery of new materials. Chemical heuristics, structure, bonding, as well as global and local symmetries are at the very foundation of materials properties. In this regard, in this research, we aim to identify functional materials by composition-structure-property understanding. Materials discovery consists of a subset of methods and design principles that go hand in hand until a desired material or property is realized. However, materials synthesis is still far from a rational design approach. Rather, materials, and especially metastable materials, have to be accessed and synthesized in an exploratory, laboratory-intensive fashion. At the same time, quantum materials discovery is a vibrant highly active field of research that has seen various leaps of progress in recent years, and that holds the promise for many more in the coming years. Here, we lay out how we are discovering new materials and new materials physics in our and other chemical physics, or physical chemistry research groups, and how chemistry and chemical synthesis play a crucial role in this process.


Transcarotid artery revascularization versus transfemoral carotid artery stenting in the Society for Vascular Surgery Vascular Quality Initiative.
Recent evidence from the Safety and Efficacy Study for Reverse Flow Used During Carotid Artery Stenting Procedure (ROADSTER) multicenter trial in high-risk patients undergoing transcarotid artery stenting with dynamic flow reversal reported the lowest stroke rate compared with any prospective trial of carotid artery stenting. However, clinical trials have selection criteria that exclude many patients from enrollment and are highly selective of operators performing the procedures, which limit generalizability. The aim of this study was to compare in-hospital outcomes after transcarotid artery revascularization (TCAR) and transfemoral carotid artery stenting (TFCAS) as reported in the Vascular Quality Initiative (VQI). The Society for Vascular Surgery VQI TCAR Surveillance Project (TSP) was designed to evaluate the safety and effectiveness of TCAR in real-world practice. Data from the initial 646 patients enrolled in the TSP from March 2016 to December 2017 were analyzed and compared with those of patients who underwent TFCAS between 2005 and 2017. Patients with tandem, traumatic, or dissection lesions were excluded. Multivariable logistic regression and 1:1 coarsened exact matching were used to analyze neurologic adverse events (stroke and transient ischemic attacks [TIAs]) and in-hospital mortality. Patients in the two procedures were matched on age, ethnicity, coronary artery disease, congestive heart failure, prior coronary artery bypass graft or percutaneous coronary intervention, chronic kidney disease, degree of ipsilateral stenosis, American Society of Anesthesiologists class, symptomatic status, restenosis, anatomic and medical risk, and urgency of the procedure. Compared with patients undergoing TFCAS (n = 10,136), those undergoing TCAR (n = 638) were significantly older, had more cardiac comorbidities, were more likely to be asymptomatic, and were less likely to have a recurrent stenosis. The rates of in-hospital TIA/stroke as well as of TIA/stroke/death were significantly higher in TFCAS compared with TCAR (3.3% vs 1.9% [P = .04] and 3.8% vs 2.2% [P = .04], respectively). In both procedures, symptomatic patients had higher rates of TIA/stroke/death compared with asymptomatic patients (TCAR, 3.7% vs 1.4% [P = .06]; TFCAS, 5.3% vs 2.7% [P < .001]). After multivariable adjustment, there was a trend of increased stroke or death rates in TFCAS compared with TCAR, but it was not statistically significant (2.5% vs 1.7%; P = .25; odds ratio, 1.75, 95% confidence interval, 0.85-3.62). However, TFCAS was associated with twice the odds of in-hospital adverse neurologic events and TIA/stroke/death compared with TCAR (odds ratio, 2.10; 95% confidence interval, 1.08-4.08; P = .03), independent of symptom status. Coarsened exact matching showed similar results. Compared with patients undergoing TFCAS, patients undergoing TCAR had significantly more medical comorbidities but similar stroke/death rates and half the risk of in-hospital TIA/stroke/death. These results persisted despite rigorous adjustment and matching of potential confounders. This initial evaluation of the VQI TSP demonstrates the ability to rapidly monitor new devices and procedures using the VQI. Although it is preliminary, this is the first study to demonstrate the benefit of TCAR compared with TFCAS in real-world practice. These results need to be confirmed by a clinical trial.


Evaluation of crush syndrome patients with extremity injuries in the 2011 Van Earthquake in Turkey.
To perform a descriptive analysis of crush syndrome patients with extremity injuries, which will be used as a reference for future disasters. In disasters like earthquake, cooperation among medical workers is very important for the follow-up and treatment of patients. Knowing the complications that may emerge with the crush syndrome is one of the responsibilities of the nurses. Descriptive analysis. The medical records of patients with crush syndrome following the 2011 Van Earthquake were retrospectively reviewed. The results were compared with the current literature. Of the 46 patients with crush syndrome who had extreme trauma, 26 (57%) were men, 20 (43%) were women, and the average age was 38.9 ± 12.5. Fasciotomy was performed in 21 of the patients due to progressive compartment syndromes. Amputations were performed in seven patients who had previously undergone a fasciotomy. Sepsis was observed in seven patients, wound infection in 18, pericardial effusion in three and pleural effusion in two. Additionally, femoral fracture was observed in one patient, tibial fractures in five, haemothorax in three, abdominal traumas in seven and pulmonary embolism in one. Wound care and antibiotic treatment are important to prevent infections in crush injury. In addition to this, dehydration and electrocardiography changes in hyperkalaemia are observed in crush syndrome. Nurses have significant responsibilities to follow up these observations and their implications. The results of this study may provide the basis for developing strategies in future for optimising attempts to rescue and the nurse care planning of survivors with crush injuries and crush syndrome after earthquakes.


Genetic predisposition to obesity affects behavioural traits including food reward and anxiety-like behaviour in rats.
Here we sought to define behavioural traits linked to anxiety, reward, and exploration in different strains of rats commonly used in obesity research. We hypothesized that genetic variance may contribute not only to their metabolic phenotype (that is well documented) but also to the expression of these behavioural traits. Rat strains that differ in their susceptibility to develop an obese phenotype (Sprague-Dawley, Obese Prone, Obese Resistant, and Zucker rats) were exposed to a number of behavioural tests starting at the age of 8 weeks. We found a similar phenotype in the obesity susceptible models, Obese Prone and Zucker rats, with a lower locomotor activity, exploratory activity, and higher level of anxiety-like behaviour in comparison to the leaner Obese Resistant strain. We did not find evidence that rat strains with a genetic predisposition to obesity differed in their ability to experience reward from chocolate (in a condition place preference task). However, Zucker rats show higher motivated behaviour for sucrose compared to Obese Resistant rats when the effort required to obtain palatable food is relatively low. Together our data demonstrate that rat strains that differ in their genetic predisposition to develop obesity also differ in their performance in behavioural tests linked to anxiety, exploration, and reward and that these differences are independent of body weight. We conclude that genetic variations which determine body weight and the aforementioned behaviours co-exist but that future studies are required to identify whether (and which) common genes are involved.


In Vitro Skin Permeation Enhancement of Sumatriptan by Microneedle Application.
Different dimensions of commercially available microneedle devices, namely, Admin- Patch(®) microneedle arrays (MN) (0.6, 0.9, 1.2 and 1.5 mm lengths) and Dermaroller(®) microneedle rollers (DR) (0.5 and 1mm lengths) were evaluated for their relative efficiency in enhancement of transdermal permeation of Sumatriptan (SMT). Solubility assessment of SMT was carried out using propylene glycol (PG), polyethylene glycol (PEG) in combination with saline (S) at different ratios and the order of solubility was found to be 70:30 > 80:20 > 90:10 %v/v in both PG:S and PEG:S. In vitro skin permeation studies were performed using PG:S (70:30 %v/v) as donor vehicle. A significant increase in cumulative amount of SMT permeated, steady state flux, permeability coefficient and diffusion coefficient values were observed after microneedle treatment, and the values were in the order of 1.5mm MN >1.2mm MN >0.9mm MN >1mm DR >0.6mm MN >0.5mm DR > passive permeation. Lag times were significantly shorter after longer microneedle application (0.24h for 1.5mm MN). Arrays were found to be superior to rollers with similar microneedle lengths in enhancing SMT permeation and may be attributed to higher density of microneedles and force of application onto skin. The in vitro flux values revealed that 2.5cm(2) area patch is sufficient for effective therapy after treatment of skin with 1.5mm MN. It may be inferred that microneedle application significantly enhances the transdermal penetration of SMT and that it may be feasible to deliver clinically relevant therapeutic levels of SMT using microneedle assisted transdermal delivery systems.