Protein expression profiling of nuclear membrane protein reveals potential biomarker of human hepatocellular carcinoma.
Complex molecular events lead to development and progression of liver cirrhosis to HCC. Differentially expressed nuclear membrane associated proteins are responsible for the functional and structural alteration during the progression from cirrhosis to carcinoma. Although alterations/ post translational modifications in protein expression have been extensively quantified, complementary analysis of nuclear membrane proteome changes have been limited. Deciphering the molecular mechanism that differentiate between normal and disease state may lead to identification of biomarkers for carcinoma. Many proteins displayed differential expression when nuclear membrane proteome of hepatocellular carcinoma (HCC), fibrotic liver, and HepG2 cell line were assessed using 2-DE and ESI-Q-TOF MS/MS. From the down regulated set in HCC, we have identified for the first time a 15 KDa cytochrome b5A (CYB5A), ATP synthase subunit delta (ATPD) and Hemoglobin subunit beta (HBB) with 11, 5 and 22 peptide matches respectively. Furthermore, nitrosylation studies with S-nitrosocysteine followed by immunoblotting with anti SNO-cysteine demonstrated a novel and biologically relevant post translational modification of thiols of CYB5A in HCC specimens only. Immunofluorescence images demonstrated increased protein S-nitrosylation signals in the tumor cells and fibrotic region of HCC tissues. The two other nuclear membrane proteins which were only found to be nitrosylated in case of HCC were up regulated ATP synthase subunit beta (ATPB) and down regulated HBB. The decrease in expression of CYB5A in HCC suggests their possible role in disease progression. Further insight of the functional association of the identified proteins was obtained through KEGG/ REACTOME pathway analysis databases. String 8.3 interaction network shows strong interactions with proteins at high confidence score, which is helpful in characterization of functional abnormalities that may be a causative factor of liver pathology. These findings may have broader implications for understanding the mechanism of development of carcinoma. However, large scale studies will be required for further verification of their critical role in development and progression of HCC.


Formation of aroma compounds during long-term frozen storage of unblanched leek (Allium ampeloprasum Var. Bulga) as affected by packaging atmosphere and slice thickness.
Content of aroma compounds and catalytic activity of lipoxygenase (LOX), hydroperoxide lyase (HPL), and alcohol dehydrogenase (ADH) were analyzed in 4- and 15-mm unblanched leek slices packed in atmospheric air (4- and 15-mm) or 100% nitrogen (N) (only 15-mm) seven times during 12 months of frozen storage (12M). Total amount of sulfur compounds was influenced by storage time, slice thickness, and atmosphere (concentration in fresh 4-mm slices = 17.8 mg/L, 4-mm 12M = 3.48 mg/L, fresh 15-mm slices = 2.48 mg/L, 15-mm 12M = 0.418 mg/L and 15-mm N 12M = 1.81 mg/L). The 4-mm slices significantly developed the most aldehydes after 12M (total amount = 9.28 mg/L) compared to 15-mm 12M (6.49 mg/L) and 15-mm N 12M (4.33 mg/L). LOX activity is positively influenced by nitrogen packaging, and HPL activity is influenced by slice thickness, whereas ADH is unaffected by both parameters.


Modulation of corticospinal excitability and intracortical inhibition during motor imagery is task-dependent.
Previous studies have clearly shown that motor imagery modulates corticospinal excitability. However, there is no clear evidence for the modulation of intracortical inhibition (ICI) during imagined task performance. The aim of this study was to use transcranial magnetic stimulation (TMS) to assess changes in corticospinal excitability and ICI during the imagined performance of two types of task. In Experiment 1, eight subjects performed phasic depression of a computer mouse button using the dominant index finger in time with a 1 Hz auditory metronome. Single and paired pulse magnetic stimuli were delivered at rest, and during the 'on' and 'off' phases of actual and imagined task performance. Motor evoked potentials (MEPs) were recorded from FDI and APB. In Experiment 2, eight subjects performed phasic isometric abduction of the dominant thumb in time with a 1 Hz auditory metronome. As before, single and paired pulse magnetic stimuli were delivered at rest, and during the 'on' and 'off' phases of actual and imagined task performance. In both experiments, the conditioning stimulus intensity was set to produce 50% inhibition at rest, to enable both increases and decreases in ICI during task performance to be detected. No significant temporal or spatial modulation of MEP amplitude or ICI was observed in Experiment 1. In contrast, MEP amplitude was significantly greater, and ICI significantly lower during the 'on' phase of imagined task performance in Experiment 2. These results are most likely related to the higher levels of target muscle activation required during actual task performance and the greater anatomical distance between target and control muscles in Experiment 2. These task characteristics may influence the observed degree of corticospinal excitability and ICI modulation.


Hand span influences optimal grip span in boys and girls aged 6 to 12 years.
The first aim was to determine whether there is an optimal grip span for determining the maximum hand grip strength in boys and girls aged 6 to 12 years and whether the optimal grip span was related to hand span. If so, the second aim was to derive a mathematical equation relating hand span and optimal grip span. A total of 123 boys (9 y +/- 2) and 70 girls (8 y +/- 2) were evaluated. Each hand was randomly tested on 10 occasions using 5 different grip spans, allowing a 1-minute rest between attempts. The hand span was measured from the tip of the thumb to the tip of the little finger with the hand opened widely. An optimal grip span to determine maximum hand grip strength was identified for both genders. Hand span and optimal grip span showed a significant linear association in the studied children. The equation relating grip span as a function of hand span in boys is formulated as y = x/4 + 0.44 and in girls as y = 0.3x - 0.52, where x is the hand span (maximal width between first and fifth fingers) and y is the optimal grip span. The results suggest that there is an optimal grip span to which the dynamometer should be adjusted when measuring hand grip strength in children. The optimal grip span was influenced by hand span in both genders.


Platelet Distribution Width: A Significant Predictor of Poor Outcome After Mechanical Thrombectomy.
Elevated platelet distribution width (PDW) is a recognized marker of platelet activity. Herein, we investigated the association between admission PDW values and clinical outcome at 3 months in acute ischemic stroke (AIS) patients undergoing mechanical thrombectomy (MT). We retrospectively collected consecutive patients diagnosed with AIS following MT from two stroke centers. PDW was measured on admission. Subjects were divided into two groups according to the clinical outcome using the modified Rankin Scale at 3 months. Multiple regression analyses and receiver operating characteristic (ROC) curves were performed to determine the associations between admission PDW values, clinical parameters, and functional outcome. A total of 162 subjects were enrolled. Patients in the poor outcome group had a significantly higher percentage of PDW >16.0 fL compared with the good outcome group (57.3% vs. 26.9%, P < 0.001). After adjusting for a range of confounding factors, multiple regression analysis showed that PDW >16.0 fL was an independent predictor of poor outcome at 3 months (odds ratio 4.572, 95% confidence interval 1.896-11.026, P = 0.001). ROC curve analysis revealed that PDW >16.0 fL predicted poor outcome with 57.3% sensitivity and 73.1% specificity (the area under the ROC curve 0.637, 95% confidence interval 0.558-0.711, P = 0.004). Elevated PDW is an independent predictor of poor functional outcome in patients with anterior circulation AIS undergoing MT at 3 months.


Effects of Problem-Solving Therapy and Clinical Case Management on Disability in Low-Income Older Adults.
To test the following hypotheses: (1) Clinical case management integrated with problem-solving therapy (CM-PST) is more effective than clinical case management alone (CM) in improving functional outcomes in disabled, impoverished patients and (2) improvement in depression, self-efficacy, and problem-solving skills mediates improvement of disability. Using a randomized controlled trial with a parallel design, 271 individuals were screened and 171 were randomized to 12 weekly sessions of either CM or CM-PST at 1:1 ratio. Raters were blind to patients' assignments. Participants were at least age 60 years with major depression, had at least one disability, were eligible for home-based meals services, and had income no more than 30% of their counties' median. The WHO Disability Assessment Scale was used. Both interventions resulted in improved functioning by 12 weeks (t = 4.28, df = 554, p = 0.001), which was maintained until 24 weeks. Contrary to hypothesis, CM was noninferior to CM-PST (one-sided p = 0.0003, t = -3.5, df = 558). Change in disability was not affected by baseline depression severity, cognitive function, or number of unmet social service needs. Improvements in self efficacy (t = -2.45, df = 672, p = 0.021), problem-solving skill (t = -2.44, df = 546, p = 0.015), and depression symptoms (t = 2.25, df = 672, p = .025) by week 9 predicted improvement in function across groups by week 12. CM is noninferior to CM-PST for late-life depression in low-income populations. The effect of these interventions occur early, with benefits in functional status maintained as long as 24 weeks after treatment initiation (clinicaltrials.gov; NCT00540865).


Exploring the fate of heavy metals from mining and smelting activities in soil-crop system in Baiyin, NW China.
The activity and fate of heavy metals (HMs) from mining and smelting activities in farmland soil is of great significance to effectively prevent the excessive enrichment of HMs in crops. This study focuses on Baiyin area, a typical mining city in northwest China. In this example, the sources, speciation, and fate of HMs in the farmland soil, and the migration and enrichment characteristics of HMs in the different parts of crops planted in different areas were studied in detail combining the chemical sequential extraction and Pb isotope approaches. Results showed that the mean anthropogenic contributions of HMs in farmland soils were approximately 85%, 88%, 76%, and 41% for the ore district (OD), Xidagou sewage irrigation area (XSIA), Dongdagou sewage irrigation area, and the Yellow River irrigation area, respectively, and the risk that HMs were excessively accumulated in crops in OD and XSIA was high. Compared with soil residual fractions, the isotope ratios 206Pb/207Pb in non-residual fractions (1.1304-1.1669) were closer to the values of local ores, suggesting that anthropogenic HMs from mining and smelting activities were mainly enriched in the non-residual fractions. The isotope ratios 206Pb/207Pb in crops (1.1398-1.1686) further confirmed that those anthropogenic HMs were more easily absorbed and concentrated by crops. HMs contents in leaves from OD and XSIA were generally higher than that in roots, suggesting that atmospheric deposition in OD and XSIA had a greater impact on the HMs concentration of crop leaves,while the excess rate of HMs in grain/fruit was the lowest in all parts of crops. The division and classification of crop planting in mining area can effectively help minimize the risk that HMs from anthropogenic source enter the human body through the food chain.


Sonography of focal foveolar hyperplasia causing gastric obstruction in an infant.
A young infant is presented with a mass partially obstructing the distal stomach. Sonography demonstrated the superficial origin of the lobulated lesion which proved to be focal foveolar hyperplasia, the most common cause of a gastric polypoid mass in adults but rare in children.


T4 gene 32 protein trypsin-generated fragments. Fluorescence measurement of DNA-binding parameters.
The intrinsic fluorescence of the T4 helix-destabilizing protein specified by gene 32 (32P) is not altered by the proteolytic removal of either the 6200-dalton COOH-terminal "A" region (32P*-A) or both the A and the 2300-dalton NH2-terminal "B" region (32P*-(A + B)). The intrinsic fluorescence of 32P, 32P*-A, and 32P*-(A + B) is decreased 23% by the addition of d(pT)8 and 34% by the addition of poly(dT). Saturation binding curves of the percentage of change in protein fluorescence as a function of nucleotide concentration show that the intact 32P as well as the two proteolysis-generated fragments all have association constants of approximately 10(6) M-1 for d(pT)8. This demonstrates that the DNA binding site is not contained within either the A or B regions of 32P. Both 32P and 32P*-A bind cooperatively to poly(dT) as evidenced by a 400- to 1000-fold increase in association constant for poly(dT) compared to d(pT)8. Since within the limits of our measurements 32P and 32P*-A bind equally well to poly(dT) (Kassoc approximately 5 . 10(8) M-1), the enhanced helix-destabilizing properties previously reported for 32P*-A cannot be accounted for by a significant increase in binding affinity of 32P*-A for single-stranded DNA. The binding constant for the 32P*-(A + B):poly(dT) complex is only 3-fold higher than that for the 32P*-(A + B):d(pT)8 complex, which confirms our proposal that the B region is essential for cooperative 32P:32P protein interactions.


Use of polyglactin 910 knitted mesh tubing to stabilize particulate hydroxyapatite in alveolar ridge augmentation. A preliminary report.
A universal problem with the use of hydroxyapatite (HA) particles has been the tendency for these particles to migrate beyond planned boundaries. This is a preliminary report on the use of polyglactin 910 knitted mesh (Vicryl) tubing containing HA particles in ridge-augmentation procedures, assessing the technique and the containment of HA particles. The technique is described and experience with six cases is presented. This study found no clinical or radiographic evidence of particle migration after normal function had been resumed. In one case the graft failed to become firmly incorporated with the bone and the whole graft migrated anteriorly on the mandible but still provided improved function for the patient. The technique facilitates the placement of HA particles and would be particularly useful if open mucosal flap techniques were being used for ridge augmentation. The use of Vicryl tubing for HA augmentation procedures prevents the migration of particles and allows an easier and more accurate placement of the grafts.


DinB (DNA polymerase IV), ImuBC and RpoS contribute to the generation of ciprofloxacin-resistance mutations in Pseudomonas aeruginosa.
We investigated the role(s) of the damage-inducible SOS response dinB and imuBC gene products in the generation of ciprofloxacin-resistance mutations in the important human opportunistic bacterial pathogen, Pseudomonas aeruginosa. We found that the overall numbers of ciprofloxacin resistant (CipR) mutants able to be recovered under conditions of selection were significantly reduced when the bacterial cells concerned carried a defective dinB gene, but could be elevated to levels approaching wild-type when these cells were supplied with the dinB gene on a plasmid vector; in turn, firmly establishing a role for the dinB gene product, error-prone DNA polymerase IV, in the generation of CipR mutations in P. aeruginosa. Further, we report that products of the SOS-regulated imuABC gene cassette of this organism, ImuB and the error-prone ImuC DNA polymerase, are also involved in generating CipR mutations in this organism, since the yields of CipR mutations were substantially decreased in imuB- or imuC-defective cells compared to wild-type. Intriguingly, we found that the mutability of a dinB-defective strain could not be rescued by overexpression of the imuBC genes. And similarly, overexpression of the dinB gene either only modestly or else failed to restore CipR mutations in imuB- or imuC-defective cells, respectively. Combined, these results indicated that the products of the dinB and imuBC genes were acting in the same pathway leading to the generation of CipR mutations in P. aeruginosa. In addition, we provide evidence indicating that the general stress response sigma factor σs, RpoS, is required for mutagenesis in this organism and is in part at least modulating the dinB (DNA polymerase IV)-dependent mutational process. Altogether, these data provide further insight into the complexity and multifaceted control of the mutational mechanism(s) contributing to the generation of ciprofloxacin-resistance mutations in P. aeruginosa.


The 4.5 S RNA gene of Escherichia coli is essential for cell growth.
The Escherichia coli gene coding for the metabolically stable 4.5 S RNA (ffs) has been shown to be required for cell viability. Essentiality was demonstrated by examining the recombination behavior of substitution mutations of ffs generated in vitro. Substitution mutants of ffs are able to replace the chromosomal allele only in the presence of a second, intact copy of ffs. Independent evidence of essentiality and the finding that 4.5 S RNA is important for protein synthetic activity came from characterization of cells dependent on the lac operon inducer isopropyl-beta-D-thiogalactoside for ffs gene expression. Here, a strain dependent on isopropyl-beta-D-thiogalactoside for 4.5 S RNA synthesis was developed by inactivation of the chromosomal ffs allele and lysogenization by a lambda phage containing 4.5 S DNA fused to a hybrid trp-lac promoter. Withdrawal of the thiogalactoside leads to a deficiency in 4.5 S RNA, a dramatic loss in protein synthesis activity, and eventual cell death. Tagging of the chromosomal ffs region with a kanamycin-resistance gene allowed mapping of the 4.5 S RNA gene. Results from this analysis place ffs near lon at approximately ten minutes on the E. coli linkage map.


Analysis of sarcoplasmic reticulum proteins in patients susceptible to malignant hyperthermia.
It has been suspected that the cause of malignant hyperthermia (MH) is an abnormality in the sarcoplasmic reticulum of skeletal muscle. We isolated the sarcoplasmic reticulum from malignant hyperthermia-susceptible (MHS) patients and controls and analysed the protein composition with sodium dodecyl sulfate polyacrylamide gel electrophoresis. There were no remarkable changes in the sarcoplasmic reticulum protein composition profile of the scanned gel of the patients. Quantitative measurement of the relative proportion of each band in the gel, however, revealed a slight decrease in calsequestrin and a slight increase in protein of molecular weight 23,000. (Ca2+ -Mg2+)ATPase had no altered subfragments in MHS patients. Crude mitochondrial proteins and myoplasmic proteins showed minor alterations in composition in some patients. The data supported the thesis that malignant hyperthermia is due to defects in several different cell membranes including the sarcoplasmic reticulum and the mitochondria.


Zinc and diabetes.
Zn2+ ions are essential for the normal processing and storage of insulin and altered pancreatic insulin content is associated with all forms of diabetes mellitus. Work of the past decade has identified variants in the human SLC30A8 gene, encoding the zinc transporter ZnT8 which is expressed highly selectively on the secretory granule of pancreatic islet β and α cells, as affecting the risk of Type 2 Diabetes. Here, we review the regulation and roles of Zn2+ ions in islet cells, the mechanisms through which SLC30A8 variants might affect glucose homeostasis and diabetes risk, and the novel technologies including recombinant targeted zinc probes and knockout mice which have been developed to explore these questions.


Real-time monitoring of nitric oxide and blood flow during ischemia-reperfusion in the rat testis.
In the present study, we attempted to clarify the role of nitric oxide (NO) and its release during the ischemia-reperfusion rat testis. Eight-week-old male Sprague-Dawley rats were divided into seven groups: age-matched control rats, ischemia (30 minutes)-reperfusion (30 minutes) rats without NG-nitro-L-arginine methyl ester (L-NAME) and L-arginine (L-Arg) treatment, ischemia (30 minutes)-reperfusion (30 minutes) rats treated with L-NAME (10, 30, and 100 mg/kg), ischemia-reperfusion rats treated with L-Arg (10 and 30 mg/kg). Sixty minutes prior to induction of ischemia, L-NAME or L-Arg was administrated intraperitoneally. Real-time monitoring of blood flow and NO release were measured simultaneously with a laser Doppler flowmeter and an NO-selective electrode, respectively. NO2-NO3 and malonaldehyde (MDA) concentrations were measured in the experimental testes. Furthermore, we investigated possible morphological changes in the testis. Clamping of the testicular artery decreased blood flow to 5-20% of the basal level measured before clamping. Immediately following clipping of the artery, NO release rapidly increased. After removing the clip, NO release gradually returned to the basal level. This phenomenon was enhanced by treatment with L-Arg and inhibited by treatment with L-NAME. NO2-NO3 concentrations were increased by treatment with L-Arg and decreased by treatment with L-NAME, while MDA concentrations were increased by treatment with L-NAME and were decreased by treatment with L-Arg. In histological studies, the ischemia-reperfusion caused infiltration of leukocytes and a rupture of microvessels in the testis. Our data suggest that NO has cytoprotective effects on ischemia-reperfusion injury in the rat testis.


Facial nerve outcomes following gamma knife radiosurgery for subtotally resected vestibular schwannomas: Early versus delayed timing of therapy.
Initially treating vestibular schwannomas (VSs) with subtotal resection (STR) followed by Gamma Knife radiosurgery (GKRS) for progression of tumor residual is a strategy that balances maximal tumor resection with preservation of neurological function. The effect of timing of GKRS for residual and recurrent VSs remains poorly defined. We developed a simple and practical treatment algorithm for the timing of GKRS after STR of VSs and reviewed our follow-up results to determine outcomes between patients treated with early vs. late GKRS. Patients that underwent STR between 1999 and 2017 for a VS at Tufts Medical Center were identified and included in the study cohort. Patients who received GKRS ≤ 12 months after STR were included in the early intervention group. Patients who received GKRS > 12 months after STR or did not have tumor progression on follow-up thus not requiring GKRS were included in the observation/delayed intervention group. STR of VSs was performed on 23 patients. Mean patient age at the time of STR was 53.0 years (range: 20-86.2). The mean follow-up was 4.2 years (range: 1 month-15.5 years). Patients most frequently presented with hearing loss. There were 5 patients (21.7 %) in the early intervention group and 18 (78.3 %) patients in the observation/delayed intervention group. Ten of 23 patients (43.5 %) required GKRS. Thirteen (56.5 %) did not receive GKRS. None of the patients in the early intervention group or the observation/delayed intervention group had changes in House-Brackmann (HB) Grade either after GKRS or at the end of the study period. GKRS of residual or recurrent tumor is safe following STR of VS and appears to carry a low risk of worsening facial nerve function when performed for progressive tumor growth.


Hierarchical Development of Physical Frailty and Cognitive Impairment and Their Association With Incident Cardiovascular Disease.
Frailty and cognitive impairment (CI) are geriatric conditions that lead to poor health outcomes among older adults with cardiovascular disease. The association between their temporal patterns of development and cardiovascular risk is unknown. This study aims to examine the 5-year cardiovascular outcomes by the pattern of development of frailty and CI in older adults without a history of coronary artery disease. We used the National Health and Aging Trends Study, linked to Medicare data. Frailty was measured using the physical frailty phenotype. CI was measured using the AD8 Dementia Screening Interview, measured cognitive performance, or self-report by patient or caregiver for a diagnosis given by a physician. The primary outcome was incident major adverse cardiovascular event at 5 years. Of a total 2,189 study participants aged 65 and older, 38.5% were male. In this study population, 154 (7%) participants developed frailty first, 829 (38%) developed CI first, and 195 (9%) participants developed both simultaneously (frail-CI group). Those who developed frailty and CI simultaneously were older, more likely to be female, and had multiple chronic conditions. The frail-CI group had the highest risk of major adverse cardiovascular event (hazard ratio [HR]: 1.81; 95% CI: 1.47-2.23) followed by frail first (HR: 1.46; 95% CI: 1.17-1.81) and CI first (HR: 1.31; 95% CI: 1.15-1.50). Frailty first was associated with the greater risk of stroke (HR: 1.49; 95% CI: 1.06-2.09) compared to the intact group. The simultaneous development of frailty and CI is associated with an increased risk of adverse cardiovascular outcomes including death compared with the development of each syndrome alone. Diagnostics to detect frailty and CI are critical in assessment of cardiovascular risk in the older population.


Human GAP-43: its deduced amino acid sequence and chromosomal localization in mouse and human.
The growth-associated protein (GAP-43) is considered a crucial component of an effective regenerative response in the nervous system. Its phosphorylation by protein kinase C correlates with long-term potentiation. Sequence analysis of human cDNAs coding for this protein shows that the human GAP-43 gene is highly homologous to the rat gene; this homology extends into the 3'-untranslated region. However, the human protein contains a 10 amino acid insert. Somatic cell hybrids demonstrate localization of the GAP-43 gene to human chromosome 3 and to mouse chromosome 16.


Vegetable Oil or Animal Fat Oil, Which is More Conducive to Cardiovascular Health Among the Elderly in China?
Our present study aimed to investigate the relationship between cooking oil types and atherosclerotic cardiovascular disease (ASCVD) and to reveal which cooking oil is more beneficial to cardiovascular health in older Chinese. This study relies on cross-section data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in the 2018 wave. A total of 15,874 elderly Chinese over 65 years old were included in our analysis. Logistic regression analysis was used to assess the association between cooking oil types and ASCVD. Of the 15,874 elderly people, 13,709 cooked with vegetable/gingili oil, with an average age [SD] of 84.47 [11.51] years; 1533 cooked with lard/other animal fat oils, with an average age [SD] of 85.90 [11.72] years. 3918 of those who cooked with vegetable/gingili oil had ASCVD, and 249 of those who cooked with lard/other animal fat oils had ASCVD. The prevalence of ASCVD in vegetable/gingili oil users (31.68%) was higher than that in lard/other animal fat oil users (17.46%). Compared with lard/other animal fat users, the multivariate-adjusted model indicated that vegetable oil/sesame oil users were significantly associated with a higher risk of ASCVD (OR = 2.19; 95%CI, 1.90-2.53). Our study found that cooking with lard/other animal fat oil is more beneficial to cardiovascular health in older Chinese. Dietary guidelines should seriously consider the health effects of substituting vegetable/gingili oil for lard/other animal fat oil for different populations.


Patient-centered clinical trials.
We apply Bayesian decision analysis (BDA) to incorporate patient preferences in the regulatory approval process for new therapies. By assigning weights to type I and type II errors based on patient preferences, the significance level (α) and power (1-β) of a randomized clinical trial (RCT) for a new therapy can be optimized to maximize the value to current and future patients and, consequently, to public health. We find that for weight-loss devices, potentially effective low-risk treatments have optimal αs larger than the traditional one-sided significance level of 5%, whereas potentially less effective and riskier treatments have optimal αs below 5%. Moreover, the optimal RCT design, including trial size, varies with the risk aversion and time-to-access preferences and the medical need of the target population.


Deletion of 7p or monosomy 7 in pediatric acute lymphoblastic leukemia is an adverse prognostic factor: a report from the Children's Cancer Group.
Monosomy 7 or deletions of 7q are associated with many myeloid disorders; however, the significance of such abnormalities in childhood acute lymphoblastic leukemia (ALL) is unknown. Among 1880 children with ALL, 75 (4%) had losses involving chromosome 7, 16 (21%) with monosomy 7, 41 (55%) with losses of 7p (del(7p)), 16 (21%) with losses of 7q (del(7q)), and two (3%) with losses involving both arms. Patients with losses involving chromosome 7 were more likely to be > or =10 years old, National Cancer Institute (NCI) poor risk, and hypodiploid than patients lacking this abnormality. Patients with or without these abnormalities had similar early response to induction therapy. Event-free survival (EFS) and survival for patients with monosomy 7 (P<0.0001 and P=0.0007, respectively) or del(7p) (P<0.0001 and P=0.0001, respectively), but not of patients with del(7q), were significantly worse than those of patients lacking these abnormalities. The poorer EFS was maintained after adjustment for a Philadelphia (Ph) chromosome, NCI risk status, ploidy, or an abnormal 9p. However, the impact on survival was not maintained for monosomy 7 after adjustment for a Ph. These results indicate that the critical region of loss of chromosome 7 in pediatric ALL may be on the p-arm.


Short-term impact of COVID-19 lockdown on metabolic control of patients with well-controlled type 2 diabetes: a single-centre observational study.
The strict rules applied in Italy during the recent COVID-19 pandemic, with the prohibition to attend any regular outdoor activity, are likely to influence the degree of metabolic control in patients with type 2 diabetes. We explored such putative effect immediately after the resolution of lockdown rules, in the absence of any variation of pharmacologic treatment. One-hundred and fourteen patients with adequate metabolic control took part in this single-centre, prospective, observational study. The metabolic profile tested 1 week after the end of the lockdown was compared with the last value and the mean of the last three determinations performed before the pandemic emergency (from 6 months to 2 years before). After 8 weeks of lockdown, an increase of HbA1c > 0.3% (mean +0.7%) was observed in 26% of the participants; these were also characterized by a persistent elevation in serum triglycerides able to predict the worsening of glucose control. Lockdown determined a relevant short-term metabolic worsening in approximately one-fourth of previously well-controlled type 2 diabetic individuals; pre-lockdown triglycerides were the only parameter able to predict such derangement of glucose control.


Predictive and prognostic roles of BRAF mutation in patients with metastatic colorectal cancer treated with anti-epidermal growth factor receptor monoclonal antibodies: a meta-analysis.
This study aimed to evaluate the predictive and prognostic roles of BRAF mutation in patients with metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs). Computer searches of the literature on BRAF mutation in mCRC patients were performed. Studies with objective response rate (ORR) to anti-EGFR MoAbs and/or overall survival (OS) and progression-free survival (PFS) with different BRAF gene expression in mCRC patients were eligible. A total of 19 studies including 2875 patients was enrolled in the meta-analysis. BRAF mutation was detected in 246 patients. The ORR was 18.4% (40/217) in mutant BRAF group and 41.7% (831/1993) in the wild-type BRAF group. The overall risk ratio (RR) for the ORR of BRAF mutation patients compared with wild-type BRAF patients was 0.58 (95% confidence intervals [CI] 0.35-0.94, P = 0.027). The median PFS of patients with BRAF mutation was significantly shorter than that of patients with wild-type BRAF (hazard ratio [HR] 2.98, 95% CI 2.07-4.27, P < 0.001) and the median OS of patients with BRAF mutation was also significantly shorter than that of those with wild-type BRAF (HR 2.85, 95% CI 2.31-3.52, P < 0.001). BRAF mutation is associated with poor response to anti-EGFR MoAbs and it is an adverse prognostic biomarker of the survival of patients with mCRC.


[Use of the "Sartorius" cutaneous absorption simulator for transdermal pharmaceutical forms of NSAIDs].
We report the results of the in vitro-release of the active ingredients (flurbiprofen and ibuprofen) from dermal form obtained by the Sartorius Absorption simulator SM16750. The results show that the choice of the excipients is basic. Using NSAID, the aqueous gel can be considered the suitable formulation to obtained a good in vitro-release. The quantities of the active ingredients released during the time are plotted in diagrams.


Calcification of basal ganglia, postoperative hypoparathyroidism and extrapyramidal, cerebellar, pyramidal motor manifestations.
A patient is described who 32 years after thyroidectomy developed a chronic progressive syndrome due to hypoparathyroidism, with multiple extrapyramidal signs (faciobuccolingual dyskinesias, choreiform and athetotic movements of upper extremities, tremor of hands, cogwheel phenomenon), cerebellar manifestations (dysarthria, dysgraphia, mild gait ataxia), and pyramidal signs as well as an organic psychosis and epilepsy. A CT scan showed calcification of the basal ganglia. Therapy for hypoparathyroidism produced partial regression of the disorder. To explain the physiopathologic mechanism of the syndrome, Selye et al. advanced an attractive hypothesis of calciphylaxis, which assumes that a sensitizer and a challenger together induce development of calcification. In the case reported calcification involved the periventricular region and was not limited to the basal ganglia. It is suggested that either a sensitizer or a challenger may enter the periventricular tissue via the ependyma.


CGG repeat expansion in LRP12 in amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the degeneration of motor neurons. Although repeat expansion in C9orf72 is its most common cause, the pathogenesis of ALS isn't fully clear. In this study, we show that repeat expansion in LRP12, a causative variant of oculopharyngodistal myopathy type 1 (OPDM1), is a cause of ALS. We identify CGG repeat expansion in LRP12 in five families and two simplex individuals. These ALS individuals (LRP12-ALS) have 61-100 repeats, which contrasts with most OPDM individuals with repeat expansion in LRP12 (LRP12-OPDM), who have 100-200 repeats. Phosphorylated TDP-43 is present in the cytoplasm of iPS cell-derived motor neurons (iPSMNs) in LRP12-ALS, a finding that reproduces the pathological hallmark of ALS. RNA foci are more prominent in muscle and iPSMNs in LRP12-ALS than in LRP12-OPDM. Muscleblind-like 1 aggregates are observed only in OPDM muscle. In conclusion, CGG repeat expansions in LRP12 cause ALS and OPDM, depending on the length of the repeat. Our findings provide insight into the repeat length-dependent switching of phenotypes.


Margin size is an independent predictor of local tumor progression after ablation of colon cancer liver metastases.
This study was designed to evaluate the relationship between the minimal margin size and local tumor progression (LTP) following CT-guided radiofrequency ablation (RFA) of colorectal cancer liver metastases (CLM). An institutional review board-approved, HIPPA-compliant review identified 73 patients with 94 previously untreated CLM that underwent RFA between March 2003 and May 2010, resulting in an ablation zone completely covering the tumor 4-8 weeks after RFA dynamic CT. Comparing the pre- with the post-RFA CT, the minimal margin size was categorized to 0, 1-5, 6-10, and 11-15 mm. Follow-up included CT every 2-4 months. Kaplan-Meier methodology and Cox regression analysis were used to evaluate the effect of the minimal margin size, tumor location, size, and proximity to a vessel on LTP. Forty-five of 94 (47.9 %) CLM progressed locally. Median LTP-free survival (LPFS) was 16 months. Two-year LPFS rates for ablated CLM with minimal margin of 0, 1-5 mm, 6-10 mm, 11-15 mm were 26, 46, 74, and 80 % (p < 0.011). Minimal margin (p = 0.002) and tumor size (p = 0.028) were independent risk factors for LTP. The risk for LTP decreased by 46 % for each 5-mm increase in minimal margin size, whereas each additional 5-mm increase in tumor size increased the risk of LTP by 22 %. An ablation zone with a minimal margin uniformly larger than 5 mm 4-8 weeks postablation CT is associated with the best local tumor control.


Orbital fractures in children: 10 years' experience from a tertiary centre.
Our aim was to examine the relations between type and site of the fracture, age of the patient, and the management and outcomes, among children diagnosed with orbital fractures at the Women's and Children's Hospital, Adelaide, during a 10-year period from 1 January 2003 to 31 December 2012. The records of 41 children whose ages ranged from 8 months to 15 years were analysed. There was a male predominance (n=33). Two most common fractures were orbital floor and multiwalled fractures, with medial wall as the second most common site. The most common cause of injury was sport, more often with increasing age. In contrast, falls were more common among young children. Fractures of the orbital roof were more common among young children, all of ours being in children 10 years old or less. Lateral wall fractures were also more common among young children and declined in frequency with increasing age. In contrast, fractures of the orbital floor and medial wall can occur at any age, though those of the medial wall were more common among older children. As children grow their behaviour and activities change, and the mechanism by which they become injured also changes. Growth and development of the craniofacial skeleton lead to differences in the patterns of fractures with age. Fractures of the orbital roof and lateral wall are more common among young children, while those of the orbital floor and medial wall can occur at any age.


Breast cancer: chemotherapy in the treatment of advanced disease.
Chemotherapy in patients with advanced breast cancer remains palliative. Although the majority of patients will experience an initial response or stabilisation of the disease, the survival is only modestly improved. The search for new drugs and more effective combinations must therefore continue. High-dose chemotherapy with or without autologous bone marrow transplant (ABMT) is an enthusiastic perspective of progress but the available data do not permit conclusions about the effectiveness of high-dose therapy compared with conventional treatment.


The acute effect of oestrogens on testosterone production appears not to be mediated by testicular oestrogen receptors.
Scatchard binding analysis was performed to measure the cytoplasmic oestrogen receptor in the testis of rats. After treatment of rats with the antioestrogen tamoxifen no oestrogen receptor binding was found in testicular low speed supernatant between 12 and 96 h after treatment. Such tamoxifen-treated rats were used to study the acute effect of oestrogens on testosterone secretion, both in vivo and in vitro. Injection of oestradiol benzoate (50 microgram, 24 h prior to experiment) resulted in a significant depression of basal and LH-stimulated plasma testosterone levels in control rats and this effect was unchanged in tamoxifen-pretreated rats. In vitro, oestradiol-17 beta also inhibited the LH-induced rise in testosterone secretion by isolated testicular interstitial cells. This inhibition was not affected if the rats had been pretreated with tamoxifen. These results indicate that the inhibitory effects of exogenous oestrogens on testicular testosterone production are probably not mediated by the oestrogen receptor.


Paroxysmal complete heart block due to bradycardia-dependent "phase 4" fascicular block in a patient with sinus node dysfunction and bifascicular block.
A 34-year-old man with ankylosing spondylitis was admitted to the hospital because of syncopal attacks and heart block. Standard ECG, telemetry and an invasive electrophysiologic examination demonstrated right bundle branch block with left anterior fascicular block, sinus node dysfunction with spontaneous slowing of the sinus rate and, as a result, complete infrahisian atrioventricular block in the remaining fascicle at sinus rates below 57 beats per minute. Infrequent supraventricular extrasystoles and abruptly terminated atrial pacing led to the same result. Atrioventricular conduction resumed after three-to-four blocked atrial impulses with successively increasing rate. Pacemaker treatment provided complete symptomatic relief.


Resilience predicts positive mental health outcomes during the COVID-19 pandemic in New Yorkers with and without obsessive-compulsive disorder.
There has been substantial concern about the mental health effects of the COVID-19 pandemic, particularly for those with obsessive-compulsive disorder (OCD) given the overlap between OCD symptoms (e.g., excessive handwashing) and appropriate disease prevention measures. However, the pandemic has demonstrated heterogeneous mental health effects, suggesting that individual-level factors could play a role in buffering or exacerbating its deleterious impact. This study aimed to understand how individual differences in resilience were associated with trajectories of obsessive-compulsive, depression, and anxiety symptoms among healthy adults and those with OCD residing in New York City, considered the epicenter of the pandemic in the United States at its onset. The sample consisted of healthy individuals (n = 30) and people with OCD (n = 33) who completed clinical interviews and self-report questionnaires that assessed baseline resilience, OCD symptoms, depression, anxiety, and perceived positive effects of the pandemic at four assessment timepoints: baseline (April 2020) and one, two, and six months later. Linear mixed-effects growth models revealed that greater resilience was associated with stable trajectories of symptoms over time. Conversely, less resilience was associated with worsening obsessive-compulsive symptoms from the two-month to six-month assessment timepoints and worsening depressive symptoms at six months across both groups, and with worsening anxiety symptoms in individuals with OCD at six months. Resilience was correlated with the ability to appreciate "silver linings" of the pandemic. These findings highlight resilience as a potential treatment target for bolstering mental health outcomes among individuals with and without psychopathology during sustained and unprecedented periods of stress.


Influence of metal cation and surface iron oxide on the transport of sulfadiazine in saturated porous media.
Sulfadiazine (SDZ) is an antibiotic frequently detected in soil and groundwater. The transport of SDZ in subsurface environment is a critical process affecting its retention in soil. To date, the effects of iron oxide and metal cation on the transport of SDZ remain largely unknown, so we investigated the transport properties of SDZ in cleaned and iron oxides coated quartz sand, as affected by the presence of conventional cations (Ca2+, Mg2+, K+, and Na+) and Cd2+ through column experiments and simulation. We found that iron oxide coating on sand surface inhibited the transport of SDZ, mainly due to hydrophobic effect, complexation, and electrostatic attraction. The inhibitory effect became more marked with increasing concentration of Cd2+. It favors the transport of Cd2+ due to the electrostatic repulsion between positively charged iron oxide and Cd2+. Ca2+ promoted the transport of SDZ in coated sand, while all the conventional cations had no effect on the transport of SDZ in cleaned sand. The increase in the concentration of Cd2+ favors the transport of SDZ in cleaned sand. However, in iron oxide coated sand, the influence of Cd2+ on the transport of SDZ was dependent on the concentration of Cd2+. At lower concentration of Cd2+ and by competition, the transport is favored. At high concentration, the transport is inhibited mainly due to the formation of ternary surface complexes. A convective-dispersive transport model was applied to simulate and interpret experimental data. Breakthrough curves fitted well with a one-site model (OSM), indicating that SDZ adsorption on the sand experiences reversible kinetic. A low level of KF values with nearly linear sorption isotherm shows high mobility of SDZ and a high potential risk of surface and groundwater contamination. However, such high mobility can be reduced by increasing the content of iron oxides in porous media.


Nuclear IGF1R is a transcriptional co-activator of LEF1/TCF.
Recent findings suggest that nuclear IGF1R binds to enhancer regions and functions as a transcriptional cofactor. However, the downstream transcriptional regulators of this pathway remain to be defined. Here, we show that nuclear IGF1R associates with the transcription factor LEF1 and increases promoter activity of LEF1 downstream target genes cyclin D1 and axin2. Furthermore, nuclear IGF1R augments protein levels of cyclin D1 and axin2. Our findings suggest a novel function for IGF1R, thus further emphasizing the important role of this receptor in cancer biology.


Regulatory demands for cost-benefit studies.
In 1987 to 1988 there was a significant increase in drug costs in Australia. This was largely the result of the introduction of angiotensin-converting enzyme inhibitors into clinical practice. In this article the implications of escalating drug costs are examined. The impact of revolutionary new drugs is considered, and it is questioned whether even a relatively wealthy country, such as Australia, can afford the high costs of these new agents. The Australian Pharmaceutical Benefits Scheme is discussed, and modification of this into a two-tier system is proposed. A two-tier system could preserve the present list and the essential elements of the current scheme but would introduce a second list of new drugs for which a premium would be charged. Such a system could recoup costs generated by new drugs and also restrict overprescribing but may limit the prescription of new drugs to less well-off persons. The article concludes by considering the total health care budget, taking into account the relative cost-benefit expenditures of hospital care and drug therapy.


Absolute and relative real-time PCR in the quantification of tst gene expression among methicillin-resistant Staphylococcus aureus: evaluation by two mathematical models.
Absolute and relative quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) by the use of two mathematical models were applied in order to study the expression of tst gene encoding the toxic shock syndrome toxin-1 (TSST-1), among methicillin-resistant Staphylococcus aureus (MRSA). Thirteen epidemic MRSA belonging to different clones and carrying a variety of toxin genes were selected. tst gene expression was achieved by using absolute and relative quantitative real-time RT-PCR and the SYBR Green I. Absolute RT-PCR showed a statistically significant higher level of tst expression among strains isolated from soft tissue infections. Relative quantification was performed in relation to 23S rRNA expression by the application of two mathematical models, the 2(-DeltaDeltaCt) and the Pfaffl analysis methods. tst gene expression was best calculated by the relative real-time RT-PCR analysis applying the Pfaffl analysis method, taking into account the reactions' efficiencies. Level of tst expression was related to patients' infection and did not depend on the MRSA genetic profile. The results indicate that the application of the Pfaffl analysis method in the evaluation of relative real-time RT-PCR is more adequate.


Ontogenesis of histamine in the chick nervous system.
Tissues from the central and peripheral nervous systems of the chick were analyzed for concentration of histamine (Hm) during development. Of the three CNS organs examined, cerebral hemispheres had the highest Hm content. Expressed on the bases of wet weight, protein, and DNA concentrations, sciatic nerve and the pineal gland had the highest levels of this biogenic amine of the five tissues investigated. The concentration of Hm was higher in the cerebellum, cerebral hemispheres, and thalamus of adult animals than in the 15 to 17-day-old embryos. The level of Hm rose markedly in the sciatic nerve and pineal gland after the 15th day of embryonic development. These data might indicate a possible involvement of Hm in controlling the course of maturation of certain organs in the nervous system.


"Self-catabolite repression" of pectate lyase in Erwinia carotovora.
The induction of pectate lyase of Erwinia carotovora was repressed by a high concentration of its inducer. The concomitant addition of cyclic adenosine 3',5'-monophosphate reversed this repression.


Blind sampling is superior to anoscope guided sampling for screening for anal intraepithelial neoplasia.
Anal cytology smears are either collected "blind" (swab inserted 4 cm into anal canal and rotated) or guided through an anoscope (transformation zone visualised and then sampled). We compared these smear techniques with respect to sample quality and patient acceptability. Using a paired, random sequence clinical trial, 151 homosexual men (n = 95 HIV positive) underwent both smear techniques at a single visit; smear order was randomised and specimens were read blind. Both techniques utilised a Dacron swab, with water lubrication. Cytological specimens were prepared using a liquid based collection method (ThinPrep). The outcome measures were cytological specimen adequacy, cytological classification, presence of rectal columnar, squamous and metaplastic cells, contamination, patient comfort and acceptability, and volume of fluid that remained after the ThinPrep procedure. Regardless of smear order, guided smears were less likely to detect higher grade abnormalities than blind smears (15 v 27 cases, p = 0.001). Controlling for smear order, guided smears were more likely to be assessed as "unsatisfactory" for cytological assessment (OR 6.93, 95% CI 1.92 to 24.94), and contain fewer squamous (OR 0.20, 95% CI 0.04 to 0.94) and metaplastic cells (OR 0.12, 95% CI 0.03 to 0.54) than blind smears; there were no other statistically significant differences between techniques. Regardless of smear technique, first performed smears were more likely to detect a higher grade abnormality than second performed smears (23 v eight cases, p < 0.001). Blind cytology smears are superior to anoscope guided smears for screening for anal neoplasia in homosexual men.


Dental age estimation using radiographic assessment of third molar eruption among 10-20-year-old Ugandan population.
This study aimed at establishing the age for third molar eruption among Ugandans aged 10-20 years. This was a cross-sectional study comprising 471 male and 541 female patients attending Mulago Dental Clinic. Patients' orthopantomographs were assessed for third molar eruption as described by Olze et al. Age was summarized using means/SD. Jaw and sex differences were assessed using Student's t-test. Complete eruption (Stage D) ranged between 13 and 20 years. The mean age at complete eruption for girls and boys was 17.5-18 years and 18.2-18.6 years, respectively. Mean age was statistically significantly (P < 0.05) lower among girls compared to boys for all third molar teeth (#18, #28, #38, and #48). The difference in mean eruption times between girls and boys was -0.62 (95% confidence interval: 0.2-1.0, P = 0.006). At 18 years, 40% or 41% maxillary and 52% or 53% mandibular molars were completely erupted. There were statistically significant differences in eruption between the sexes and jaws for all teeth (P < 0.05). Given the fact that the percentage of erupted third molars by age 18 was found to be <50% on an average in this Ugandan population, we should reconsider the use of third molar eruption as a definitive tool for age estimation in this population.


Antivirals With Adjunctive Corticosteroids Prevent Clinical Progression of Early Coronavirus 2019 Pneumonia: A Retrospective Cohort Study.
This is a retrospective cohort study of hospitalized adults with coronavirus disease 2019 (COVID-19). Fifty-seven patients received treatment alone, and 35 patients received treatment with adjunctive prednisolone. A combination of corticosteroids and antivirals was associated with lower risk of clinical progression and invasive mechanical ventilation or death in early COVID-19 pneumonia.


Schistosomiasis mansoni: blockage of cercarial skin penetration by chemical agents: i. naphthoquinones and derivatives.
Skin penetration by Schistosoma mansoni cercariae may be blocked by 1,4-and 1,2-naphthoquinones applied topically. Of 23 naphthoquinone derivatives synthesized, 15 afforded almost complete protection when applied in solution to the tails of mice 24 hours before exposure to cercariae. On the basis of present evidence the 5-carbon atom side chain present in naturally occurring lapachol seems to be important for activity, and this is in accord with the previous observation that effective protective agents are liposoluble. Topically applied cercarial penetration inhibitors are presently the only prophylactic agents available for use in the field.


Medium optimization based on the metabolic-flux spectrum of recombinant Escherichia coli for high expression of human-like collagen II.
Recombinant Escherichia coli BL21 was used to produce human-like collagen II in fed-batch cultivation. By performing MFA (metabolic-flux analysis), the carbon/nitrogen molar ratios in both the batch and feeding media were optimized for high-level production of human-like collagen II. Three carbon/nitrogen molar ratios in both the batch and feeding media were used in the present study, and the MFA results showed that the optimal carbon/nitrogen molar ratios for the batch and feeding media were 2.36:1 and 5.12:1 respectively, yielding the highest dry-cell density (67.2 g/l dry cell weight) and human-like collagen production (10.8 g/l).


Comparison of clinical benefits of clopidogrel therapy in patients with acute coronary syndromes taking atorvastatin versus other statin therapies.
In clinical practice, we found no significant difference between atorvastatin therapy or other statin therapies in the clinical outcomes of patients with acute coronary syndromes receiving clopidogrel therapy. In patients receiving atorvastatin therapy, clopidogrel therapy was associated with a significant decrease in mortality and stroke during univariate analysis and a moderate trend of reduced mortality and stroke without statistical significance in the multivariate analysis.


Role of IL-17 in psoriasis and psoriatic arthritis.
The role of T cell subpopulations in human disease is in a transition phase due to continuous discovery of new subsets of T cell, one of which is Th17, characterized by the production of signature cytokine IL-17. In the last couple of years, many articles are coming out on the role of Th17 and its signature cytokine IL-17 in different autoimmune diseases like rheumatoid arthritis, psoriasis, psoriatic arthritis (PsA), SLE and multiple sclerosis. Psoriasis and PsA are immune-mediated diseases, affecting the skin and joints, respectively. Initially, it was thought that psoriasis and PsA were Th1-mediated diseases; however, studies in knockout animal models (IL-17 knockout mice) as well as human experimental data indicate that Th17 and its signature cytokine IL-17 have a critical role in the pathogenesis of psoriatic disease. Th17 cells have been identified from the dermal extracts of psoriatic lesions. Subsequently, our research group has substantiated this observation that Th17 cells are enriched in the papillary dermis of psoriatic plaques and in freshly isolated effector T lymphocytes from the synovial fluid of PsA patients, and we have reported that the majority of these CD4 + IL-17+ T cells are of memory phenotype (CD4RO(+)CD45RA(-)CD11a(+)). Recent reports also suggest that the synovial tissue in psoriatic arthritis is enriched with IL-17R, and its most well recognized receptor IL-17RA is functionally active in psoriatic arthritis. In this review article, we have discussed the role of IL-17 in psoriatic disease and have narrated about the novel IL17/IL-17R antibodies currently in preparation for its therapeutic uses in autoimmune diseases.


Guide bone regeneration (GBR) reconstruction of extensive alveolar bone defect due to infected radicular cyst enucleation: 2 case reports.
Reconstruction of alveolar bone defects caused by radicular cysts is challenging for oral and maxillofacial surgeons. Two Indonesian females had similar complaint of swelling in the vestibule area of the right mandible. Panoramic radiography showed radiolucent lesions. Participants underwent guided bone regeneration (GBR) reconstruction, which used pericardium membrane in the first case and amnion membrane in the second case. Post-surgery condition showed an improved prognosis and histology showed a radicular cyst. The use of pericardium membrane is easier compared to the amnion membrane, where success requires regular follow-up. Alveolar bone defect reconstruction based on GBR requires meticulous preparation regarding patient condition, case selection and technical comprehension to ensure better treatment outcomes.


Rapid evolution of hosts begets species diversity at the cost of intraspecific diversity.
Ecosystems are complex food webs in which multiple species interact and ecological and evolutionary processes continuously shape populations and communities. Previous studies on eco-evolutionary dynamics have shown that the presence of intraspecific diversity affects community structure and function, and that eco-evolutionary feedback dynamics can be an important driver for its maintenance. Within communities, feedbacks are, however, often indirect, and they can feed back over many generations. Here, we studied eco-evolutionary feedbacks in evolving communities over many generations and compared two-species systems (virus-host and prey-predator) with a more complex three-species system (virus-host-predator). Both indirect density- and trait-mediated effects drove the dynamics in the complex system, where host-virus coevolution facilitated coexistence of predator and virus, and where coexistence, in return, lowered intraspecific diversity of the host population. Furthermore, ecological and evolutionary dynamics were significantly altered in the three-species system compared with the two-species systems. We found that the predator slowed host-virus coevolution in the complex system and that the virus' effect on the overall population dynamics was negligible when the three species coexisted. Overall, we show that a detailed understanding of the mechanism driving eco-evolutionary feedback dynamics is necessary for explaining trait and species diversity in communities, even in communities with only three species.


Detectability of neural tracts and nuclei in the brainstem utilizing 3DAC-PROPELLER.
Despite clinical importance of identifying exact anatomical location of neural tracts and nuclei in the brainstem, no neuroimaging studies have validated the detectability of these structures. The aim of this study was to assess the detectability of the structures using three-dimensional anisotropy contrast-periodically rotated overlapping parallel lines with enhanced reconstruction (3DAC-PROPELLER) imaging. Forty healthy volunteers (21 males, 19 females; 19-53 years, average 23.4 years) participated in this study. 3DAC-PROPELLER axial images were obtained with a 3T-MR system at four levels of the brainstem: the lower midbrain, upper and lower pons, and medulla oblongata. Three experts independently judged whether five tracts (corticospinal tract, medial lemniscus, medial longitudinal fasciculus, central tegmental and spinothalamic tracts) and 10 nuclei (oculomotor and trochlear nuclei, spinal trigeminal, abducens, facial, vestibular, hypoglossal, prepositus, and solitary nuclei, locus ceruleus, superior and inferior olives) on each side could be identified. In total, 240 assessments were made. The five tracts and eight nuclei were identified in all the corresponding assessments, whereas the locus ceruleus and superior olive could not be identified in 3 (1.3%) and 16 (6.7%) assessments, respectively. 3DAC-PROPELLER seems extremely valuable imaging method for mapping out surgical strategies for brainstem lesions.


Vagus Nerve Stimulation for Treatment-Resistant Depression: a Case Series of Clinical Symptoms Associated with the End of Service Period.
This work describes the clinical symptoms associated with end of service (EOS) of the batteries of vagus nerve stimulation (VNS) generators in treatment-resistant depression (TRD). Because neurostimulator software may not provide reliable information on battery depletion, careful monitoring of clinical symptoms during the EOS period is an important concern in the follow-up of TRD patients treated with VNS therapy. Twenty-six (26) patients were implanted and followed at the Centre Hospitalier de l'Université de Montréal. Fourteen (14) patients required battery replacement and we retrieved chart data up to 3 months before generator battery replacement. Our study demonstrated there might be a decrease or increase in VNS associated physical side effects, and possibly an increase in depressive symptoms during EOS. Our observations are limited by the retrospective nature of this small case series, and larger prospective studies evaluating both VNS side effects and depressive symptoms are therefore needed to further validate those findings. Our study is the first to examine clinical symptoms associated with EOS of the batteries of VNS in TRD.


Nitric oxide-driven nanotherapeutics for cancer treatment.
Nitric oxide (NO) is a gaseous molecule endowed with diverse biological functions, offering vast potential in the realm of cancer treatment. Considerable efforts have been dedicated to NO-based cancer therapy owing to its good biosafety and high antitumor activity, as well as its efficient synergistic therapy with other antitumor modalities. However, delivering this gaseous molecule effectively into tumor tissues poses a significant challenge. To this end, nano drug delivery systems (nano-DDSs) have emerged as promising platforms for in vivo efficient NO delivery, with remarkable achievements in recent years. This review aims to provide a summary of the emerging NO-driven antitumor nanotherapeutics. Firstly, the antitumor mechanism and related clinical trials of NO therapy are detailed. Secondly, the latest research developments in the stimulation of endogenous NO synthesis are presented, including the regulation of nitric oxide synthases (NOS) and activation of endogenous NO precursors. Moreover, the emerging nanotherapeutics that rely on tumor-specific delivery of NO donors are outlined. Additionally, NO-driven combined nanotherapeutics for multimodal cancer theranostics are discussed. Finally, the future directions, application prospects, and challenges of NO-driven nanotherapeutics in clinical translation are highlighted.


Wittgenstein running: neural mechanisms of collective intentionality and we-mode.
In this paper we discuss the problem of the neural conditions of shared attitudes and intentions: which neural mechanisms underlie "we-mode" processes or serve as precursors to such processes? Neurophysiological and neuropsychological evidence suggests that in different areas of the brain neural representations are shared by several individuals. This situation, on the one hand, creates a potential problem for correct attribution. On the other hand, it may provide the conditions for shared attitudes and intentions.


Concentration and potential health risks of trace metals in warty crab (Eriphia verrucosa Forskal, 1775) from Southern Coasts of the Black Sea, Turkey.
The drastic increase of human population and industrial wastes mostly affects coastal areas. Crabs with limited mobility, especially in benthic regions of the coasts, are more affected by metal pollution. Monitoring of trace metals in terms of food safety and potential health risks is important for consumers. Warty crab (Eriphia verrucosa) samples were collected with trammel nets between July 2015 and June 2016. The crab extracts were analyzed by an ICP-MS optical emission spectrophotometer. Trace metal densities of crab meats in the present study were determined in the order of Zn > Cu > Fe > As > Al > Mn > Hg > Pb ≥ Cd. These levels were below the acceptable values reported by the Turkish Food Codex and the EU Commission. The target hazard quotient (THQ) was above 1 in terms of As, Cu, and Hg trace metals in both groups. This study showed that although the level of trace metal was below allowable values, consumption of warty crab more than once a month may cause metal toxicity according to potential health risk analyses.


Role of precursors mixing sequence on the properties of CoMn2O4 cathode materials and their application in pseudocapacitor.
In this study, the effect of oxygen vacancy in the CoMn2O4 on pseudocapacitive characteristics was examined, and two tetragonal CoMn2O4 spinel compounds with different oxygen vacancy concentrations and morphologies were synthesized by controlling the mixing sequence of the Co and Mn precursors. The mixing sequence was changed; thus, morphologies were changed from spherical nanoparticles to nanoflakes and oxygen vacancies were increased. Electrochemical studies have revealed that tetragonal CoMn2O4 spinels with a higher number of oxygen vacancies exhibit a higher specific capacitance of 1709 F g-1 than those with a lower number of oxygen vacancies, which have a higher specific capacitance of 990 F g-1. Oxygen vacancies create an active site for oxygen ion intercalation. Therefore, oxidation-reduction reactions occur because of the diffusion of oxygen ions at octahedral/tetrahedral crystal edges. The solid-state asymmetric pseudocapacitor exhibits a maximum energy density of 32 Wh-kg-1 and an excellent cyclic stability of nearly 100%.


Contrasting lifestyles of rolling-circle phages and plasmids.
The rolling-circle mechanism of DNA replication is used by small prokaryotic genomes, such as single-stranded phages and plasmids. However, phages and plasmids have adapted the rolling-circle mechanism differently to suit their contrasting biological needs. The phi X174 phage uses a monomeric initiator protein catalytically, displays incomplete termination and recycles the initiator protein, in order to mass-produce phage progeny. By contrast, to control replication precisely, the pT181 plasmid uses a dimeric initiator protein stochiometrically, completes termination and inactivates the initiator after each replication cycle. The phi X174 phage and the pT181 plasmid represent paradigmatic adaptations of the rolling-circle mechanism and could provide models for other replicons.


Origin of Oligodendrocytes in the Vertebrate Optic Nerve: A Review.
One of the unsolved problems in the research field of oligodendrocyte (OL) development has been the site(s) of origin of optic nerve OLs and its precursor cells (OPCs). It is generally accepted that OLs in the optic nerve are derived from the brain, and thus optic nerve OLs are immigrant cells. We previously demonstrated the brain origin of optic nerve OPCs in chick embryos. However, the site of optic nerve OPC origin has not been examined experimentally in developing rodents for the past two decades. We have recently reported that optic nerve OPCs in mice arise in the preoptic area by E12.5 and gradually migrate caudally and enter the optic nerve. These OPCs give rise to myelinating OLs in the optic nerve in the postnatal or adult stages. Surprisingly, there are species differences with respect to the origin of optic nerve OPCs between chicks and mice. Here, we summarize the site of OPC origin in the optic nerve based on our own previous and recent results, and discuss possible mechanisms underlying these species differences.


Villous explant culture using early gestation tissue from ongoing pregnancies with known normal outcomes: the effect of oxygen on trophoblast outgrowth and migration.
Early placental and embryo development occur in a physiologically low oxygen environment, with a rise in oxygen tension within the placenta towards the end of the first trimester. Oxygen is implicated in the regulation of trophoblast differentiation and invasion. This study examined the effects of oxygen tension on extravillous trophoblast outgrowth and migration from normal pregnancies free of significant pathology. Early gestation villous tissue (11-14 weeks gestation), obtained by chorionic villus sampling, was cultured in 3 or 20% oxygen. Maternal and fetal outcomes were ascertained for all samples. The frequency and amount of trophoblast outgrowth and migration from villi were measured for up to 192 h. Significantly fewer explants produced outgrowths in 3% compared with 20% oxygen. The number of sites of trophoblast outgrowth and the extent of migration were also significantly less in 3% compared with 20% oxygen. In vitro hypoxia/reoxygenation further reduced trophoblast growth compared with 3% oxygen alone. HLA-G expression in extravillous trophoblasts was not affected by oxygen tension, with HLA-G positive extravillous trophoblasts being universally Ki67 negative. Human placental villi and extravillous trophoblasts in the late first trimester of pregnancy are sensitive to oxygen tension, with low oxygen inhibiting extravillous trophoblast outgrowth and migration.


The ultrastructure of multilamellar bodies and surfactant in the human lung.
Normal tissues from human lungs were dehydrated through Epon 812 resin to retain many of the lipids and carbohydrates in thin section. The three-dimensional structure of the multilamellar body was determined. The paired layer of phospholipid heads (PH) is 36 A thick; the layer of fatty-acid tails (FA) is 31 A, the same as reported previously for non-human primates and rodents. The human multilamellar body is apparently unique: the lamellae of the major focus divide into two or three lamellae; the matrix material of the core is without vesicular bodies and a projection core is present. When compared with those of the rat, human tissues contain a greater number of lamellar foci and fewer lamellae per focus. The presence of a peripheral layer of lamellae, an ever-present external limiting membrane, and the fusion of multilamellar bodies are also characteristic. Tubular myelin surfactant has the same appearance as in other mammals. Multilamellar bodies were observed in direct communication with Golgi vesicles. Their origin from multivesicular bodies and their maturation through secretion and exocytosis were demonstrated. Untransformed multilamellar bodies in the alveolar space demonstrated three periodicities (P): (1) compact regular lamellae, PH = 36 A, FA = 36 A, FA = 31 A, P = 66 A; (2) compact broad lamellae, PH = 72 A, FA = 22 A, P = 94 A; (3) loose lamellae, PH = 36 A, FA = 31 A with a variable interlamellar space.


Primary squamous cell carcinoma of the colon arising in a villous adenoma.
The first case of pure squamous cell carcinoma arising in a villous adenoma of the cecum is reported, and the literature of squamous cell carcinoma of the colon is reviewed. The possible origin of this neoplasm in adenomas of the colon, similar to that of adenocarcinoma, is discussed, and the site distributions of adenocarcinoma and squamous cell carcinoma are compared. The distribution of primary colonic squamous cell carcinoma is found to be predominantly right-sided in comparison to adenocarcinoma (p less than 0.05). Although this result does not preclude adenomas as the origin of most squamous cell carcinomas, it suggests the influence of as yet unknown site-asymmetric factors that are different from those for adenocarcinoma.


Assessing the impacts of Best Management Practices on nitrate pollution in an agricultural dominated lowland catchment considering environmental protection versus economic development.
Water quality is strongly affected by nitrate inputs in agricultural catchments. Best Management Practices (BMPs) are alternative practices aiming to mitigate the impacts derived from agricultural activities and to improve water quality. Management activities are influenced by different governmental policies like the Water Framework Directive (WFD) and the Renewable Energy Sources Act (EEG). Their distinct goals can be contrasting and hamper an integrated sustainable development. Both need to be addressed in the actual conjuncture in rural areas. Ecohydrological models like the SWAT model are important tools for land cover and land use changes investigation and the assessment of BMPs implementation effects on water quality. Thus, in this study, buffer strip, fertilization reduction and alternative crops were considered as BMPs and were implemented in the SWAT model for the Treene catchment. Their efficiency in terms of nitrate loads reduction related to implementation costs at the catchment scale was investigated. The practices correspond to the catchment conditions and are based on small and mid areal changes. Furthermore, the BMPs were evaluated from the perspective of ecologic and economic policies. The results evidenced different responses of the BMPs. The critical periods in winter were addressed by most of the BMPs. However, some practices like pasture land increase need to be implemented in greater area for better results in comparison to current activities. Furthermore, there is a greater nitrate reduction potential by combining BMPs containing fertilization reduction, buffer strips and soil coverage in winter. The discussion about efficiency showed the complexity of costs stipulation and the relation with arable land and yield losses. Furthermore, as the government policies can be divergent an integrated approach considering all the involved actors is important and seeks a sustainable development.


Inactivation by the mitotic inhibitor NY 3170 of human cells in vitro.
Inactivation of NHIK 3025 cells ny the mitotic inhibitor NY 3170 (1-propargyl-5-chloropyrimidin-2-one) was measured as loss of colony-forming ability. NY 3170 at a concentration of 0.15 nM allowed no formation of colonies after 12 days of continuous exposure to the drug. Metaphase arrest after treatment with NY 3170 was reversible if the drug was removed immediately after the onset of the arrest. When the cells were kept in mitosis by the presence of NY 3170, inactivation was complete after 8h incubation of mitotic cells with 0.4 nM NY 3170. Using synchronized cell populations, it was shown that mitosis is by far the most sensitive stage of the cell cycle to inactivation by NY 3170. This leads to the suggestion that there is a connection between the inactivating and the metaphase-arresting effect of this drug. The age response curves show that after mitosis the stages in order of decreasing sensitivity to NY3170 are: G2, late S, early S and G1. This is a similar age response to that reported for proliferating cells treated with bleomycin, whereas the mitotic inhibitors vincristine and vinblastine have shown qhite different age response curves.


Brief interventions for patients with alcohol-related trauma.
Patients who have sustained alcohol-related injuries are frequently treated in departments of oral and maxillofacial surgery. Often, an alcohol intervention will not be possible in accident and emergency departments due to intoxication but, when attending out-patient clinics for follow-up, patients are usually sober. This presents a unique opportunity for encouraging patients to review their alcohol consumption at a time when their facial injury may make them more receptive to advice. This article reviews the convincing evidence of the effectiveness of advice and brief interventions designed to be incorporated into standard out-patient consultations and describes practical screening of patients for harmful drinking, the Stages of Change Model of behaviour change and motivational interviewing for facilitating behavioural change.


Development of a Remote Monitoring Application to Improve Care and Support Patients in the First 30 Days Following Colorectal Cancer Surgery.
To design and develop a digital monitoring application to support and improve the care of patients in the first 30 post-operative days following colorectal cancer surgery. Patient interviews, health professional focus groups, patient co-creation activities, and health professional prioritization discussions. The structured and iterative co-design activities adopted in this study with key stakeholders, including patients and health professionals, lead to the development of a prototype application (app) to support patients at home during the first 30 days following surgery for colorectal cancer. A similar approach could be implemented to develop comparable apps for patients with other cancer diagnoses requiring different surgical procedures. Further research should focus on the continued development and testing of this app in relation to patient care and outcomes as well as the app's affect on nursing and other health services. Clinical implementation of remote monitoring following discharge home after surgery for colorectal cancer gives patients the opportunity to report issues of concern to relevant health professionals. This could facilitate the early identification of concerning signs and symptoms, ensuring appropriate and timely interventions to minimize readmission rates. Patients' experiences during the recovery period could also be improved through the provision of reliable and relevant online information. More specifically, health professionals could easily identify those patients requiring additional support to manage their recovery, for example, those with more severe symptoms or problems, facilitating the direction of appropriate health services to those most in need of their expertise.


Longitudinal trajectories of smoking status using 25 year annually-updated data and all-cause mortality followed over 30 years: A community-based prospective cohort study.
We aimed to evaluate the long-term risk of smoking for all-cause mortality according to smoking status trajectories using 25-year annually-repeated input, traced by group-based trajectory modeling with an extension to account for non-random participant attrition or truncation due to death. We examined 2682 men and 4317 women aged 40 to 59 years who participated in annual health checks for the community-based prospective cohort study, 1975-1984 enrollment in Japan. The main outcome measure was all-cause mortality (follow-up period: median 30.2 years in men and 32.2 years in women). We traced annual smoking trajectories, stratified by sex and smoking status at baseline. For smokers at baseline, we identified five trajectories in both sexes, with different patterns of smoking cessation (e.g., early quitters and lifelong smokers). We calculated HRs and 95% CI of all-cause mortality using Cox proportional hazards regression modeling adjusted for age, body mass index, alcohol intake, blood pressure category, dyslipidemia and glucose category. Compared with one-time-point-based smokers, trajectory-based lifelong smokers had an increased risk of all-cause mortality; HRs were 1.31 (95% CI, 1.18-1.46) in men and 1.26 (95% CI, 0.91-1.73) in women. Among community residents aged 40 to 59 years, 25-year-trajectory-based lifelong smokers had an approximately 30% increased risk for all-cause mortality compared to one-time-point-based smokers. Risk of all-cause mortality among smokers with earlier cessation varied materially. It is necessary to consider the trajectories of smoking status to clarify the long-term excess risk of smoking.


The introduction of L-phenylalanine into antimicrobial peptide protonectin enhances the selective antibacterial activity of its derivative phe-Prt against Gram-positive bacteria.
Protonectin was a typical amphiphilic antimicrobial peptide with potent antimicrobial activity against Gram-positive and Gram-negative bacteria. In the present study, when its eleventh amino acid in the sequence was substituted by phenylalanine, the analog named phe-Prt showed potent antimicrobial activity against Gram-positive bacteria, but no antimicrobial activity against Gram-negative bacteria, indicating a significant selectivity between Gram-positive bacteria and Gram-negative bacteria. However, when Gram-negative bacteria were incubated with EDTA, the bacteria were susceptible to phe-Prt. Next, the binding effect of phe-Prt with LPS was determined. Our result showed that LPS could hamper the bactericidal activity of phe-Prt against Gram-positive bacteria. The result of zeta potential assay further confirmed the binding effect of phe-Prt with LPS for it could neutralize the surface charge of E. coli and LPS. Then, the effect of phe-Prt on the integrity of outer membrane of Gram-negative bacteria was determined. Our results showed that phe-Prt had a much weaker disturbance to the outer membrane of Gram-negative bacteria than the parent peptide protonectin. In summary, the introduction of L-phenylalanine into the sequence of antimicrobial peptide protonectin made phe-Prt show significant selectivity against Gram-positive bacteria, which could partly be attributed to the delay effect of LPS for phe-Prt to access to cell membrane. Although further study is still needed to clarify the exact mechanism of selectivity, the present study provided a strategy to develop antimicrobial peptides with selectivity toward Gram-positive and Gram-negative bacteria.


Changes in heart rate variability during TOVA testing in patients with major depressive disorder.
The aim of this study was to identify major depressive disorder (MDD) based on heart rate variability (HRV) during tests of variables of attention (TOVA). Forty-five MDD patients without cardiovascular disease and 45 controls matched by age and gender participated in this study. Compared to the controls, the MDD group had lower resting HRV parameters, more omissions and variability and longer response times on TOVA, and failure of attention employment to decrease HRV. The resting HRV parameters may provide easily measured, clinically useful ways to identify patients with MDD and to monitor their progress in treatment.


Factors enhancing lycopene production by a new Mycobacterium aurum mutant.
A mutant strain of Mycobacterium aurum was isolated that produced mainly lycopene (>80%) with a total carotenoid content of 1.2 mg g(-1) dry biomass when grown on yeast extract and glucose. Lycopene content of the cells could be significantly increased, up to 7.4 mg g(-1) biomass, by growing the cells at suboptimal initial culture pH (pH 6-6.4) or by using high salt concentration (85 mM NaCl) in the culture medium, although a 25-40% decrease in biomass production occurred in both cases. Highestproductivity (4 mg lycopene l(-1) d(-1)) was obtained by cultivating the cells at pH 6.


Beneficial effects of inhaled nitric oxide in adult cardiac surgical patients.
Pulmonary hypertension with associated right ventricular dysfunction may complicate the postoperative cardiac patient despite maximum pharmacologic and ventilatory support. The purpose of this study was to retrospectively review our experience with inhaled nitric oxide (INO) in adult postoperative cardiac patients with pulmonary hypertension. We retrospectively reviewed the medical records of 17 adult cardiac patients treated with INO postoperatively between November 1998 and February 2000. The INO was used to manage pulmonary hypertension postoperatively in patients who had undergone coronary artery bypass graft (CABG) (n = 13), valve operation (n = 3), and combined CABG/aortic valve replacement (n = 1). Hemodynamic and respiratory measurements before INO and again 6 hours after administration were examined. Student's t test was used to analyze the data. Inhaled nitric oxide (20 ppm to 30 ppm) was administered for a median duration of 30.2 hours. The group, as a whole, demonstrated a significant decrease in both mean pulmonary artery pressure and right ventricular stroke work index. In addition, a significant increase in posttherapeutic cardiac index and Pao2/Fio2 ratio was observed. The vasodilatory effects of nitric oxide were specific to the pulmonary circulation as no significant change in mean arterial pressure was noted. Overall mortality was 6%. Inhaled nitric oxide effectively and selectively lowered right ventricular afterload and right ventricular work in critically ill adult cardiac patients with acute pulmonary hypertension.


Surface-enhanced Raman scattering detection of dibenzothiophene and its derivatives without π acceptor compound using multilayer Ag NPs modified glass fiber paper.
Dibenzothiophene (DBT) and its derivatives are important constituents of organosulfur compound in fossil fuels, which can result in one type of "acid rain" after burning process. Several technologies and methods have been developed to detect DBT, but they can be sophisticated and expensive. We have developed a two-step in-situ reduction method to fabricate Ag NPs modified glass fiber paper for SERS detection of DBT and its derivatives in a convenient and cheap way. Different from previous reports showing DBT cannot be detected by SERS, the substrate fabricated by our method revealed DBT's characteristic Raman peak at 1600 cm-1. The dense and multilayer Ag NPs on glass fiber provided abundant spatial surface for DBT absorption and chemical interaction with Ag NPs, which led to CHEM enhancement in SERS detection. The mechanism was verified by UV-visible absorption spectrum and calculated Raman spectra. There was a good linear relationship between the SERS intensity at 1600 cm-1 and the concentration of DBT solution between 1 × 10 -5 and 1 × 10-3 mol/L and the limit of detection was 1 × 10-6 mol/L. Spiked petrol sample was detected and the recovery rate of DBT is in the range of 94.53%-107.39%. This method provides a convenient and reliable way to detect DBT and its derivatives.


Behavioural endocrinology: no hormonal response in tied fights.
Androgens are the principal sex steroids controlling reproduction and aggression in male fish, but their production can also be affected by social interactions. Here we show that androgen concentrations are not significantly increased in cichlid fish (Oreochromis mossambicus) that are fighting their own image in a mirror, despite their aggressive behaviour towards the virtual intruder. Our results indicate that the hormonal response normally triggered in male contests is not induced under these circumstances by the act of fighting itself, and that it may therefore depend on some indicator of relative fighting ability that cannot be delivered by a mirror-image challenger.


Combination modality therapy in lung cancer: a survival study showing beneficial results of AMCOF (adriamycin, methotrexate, cyclophosphamide, oncovin and 5-fluorouracil).
Thirty-seven patients with advanced or recurrent lung cancer were randomized to cytoxan (CTX) alone, COMF (CTX, oncovin, methotrecate and 5-FU) or AMCOF (adriamycin, methotrexate, CTX, oncovin and 5-FU) after receiving radiation therapy to primary and bulky tumor sites. Median survival was 3 months for CTX, 6 months for COMF and 14 months for AMCOF. Analysis of those with cell (small cell) carcinoma showed median survival of 8.5 months. Oat cell cases treated with CTX survived 5 months (8 patients) with COMF 7.5 months (15 patients) and with AMCOF 13 months (14 patients). The median survival of those with adenocarcinoma or epidermoid carcinoma treated with CTX survived 3 months, with COMF 6 months and with AMCOF 15.5 months. Toxicity was moderate though no life-theatening toxicity developed in spite of the protocol design of escalation to achieve some degree of hematologic toxicity in all patients.


Propulsive design principles in a multi-jet siphonophore.
Coordination of multiple propulsors can provide performance benefits in swimming organisms. Siphonophores are marine colonial organisms that orchestrate the motion of multiple swimming zooids for effective swimming. However, the kinematics at the level of individual swimming zooids (nectophores) have not been examined in detail. We used high-speed, high-resolution microvideography and particle image velocimetry of the physonect siphonophore Nanomia bijuga to study the motion of the nectophores and the associated fluid motion during jetting and refilling. The integration of nectophore and velum kinematics allow for a high-speed (maximum ∼1 m s-1), narrow (1-2 mm) jet and rapid refill, as well as a 1:1 ratio of jetting to refill time. Scaled to the 3 mm nectophore length, jet speeds reach >300 lengths s-1 Overall swimming performance is enhanced by velocity gradients produced in the nectophore during refill, which lead to a high-pressure region that produces forward thrust. Generating thrust during both the jet and refill phases augments the distance traveled by 17% over theoretical animals, which generate thrust only during the jet phase. The details of velum kinematics and associated fluid mechanics elucidate how siphonophores effectively navigate three-dimensional space, and could be applied to exit flow parameters in multijet underwater vehicles.


"Take the active option" to support Healthy Lungs for Life.
ERS/ELF say "take the active option" for Healthy Lungs for Life http://ow.ly/R1WaX.


Work retention and nonspecific low back pain.
A cohort study of patients with nonspecific low back pain (LBP) participated in a 4-week multidisciplinary rehabilitation program. To identify factors that predict work retention 24 months after treatment in patients with nonspecific LBP. There is evidence that select physical, psychologic, and psychosocial factors are related to positive outcome for work-related nonspecific LBP. However, there is very little information related to work retention following an episode of nonspecific LBP. This is an exploratory study to identify select physical and psychosocial factors related to work retention. Patients who returned to work after treatment (n = 67) were followed for 2 years. Physical baseline measures included tests of flexibility, strength, and functional capacity. Psychosocial baseline measures were The Symptoms Checklist 90-R, The Pain Beliefs and Perceptions Inventory, The Oswestry Scale of perceived disability, The Work Stress Inventory, and The Quality of Life Scale. All physical parameters, perceived disability, and quality of life were tested before and after treatment. The dependent variable, work retention, was defined as the number of days that the subject worked during the 2-year follow-up period. Survival analysis was used to establish the predictive model. The average time out of work before treatment was 9 months (standard deviation 12.8) for 67 subjects (mean age 40 years [standard deviation 9.6]), including 18 females and 49 males. There were 18 participants (25%) that had interruption of work retention at follow-up. Average work retention was 362 days (range 47-682). Variables that reached a P value of <0.10 in the bivariate analysis were included in the multivariate analysis. They were trunk flexion (hazard ratio [HR = 2.4], 95% confidence interval [CI] 1.24-4.38; P = 0.01), trunk extension (HR = 2.1, 95% CI 1.02-4.16; P = 0.04), the somatization scale from the Symptom Checklist 90 revised (HR = 2.0, 95% CI 1.03-4.05; P = 0.04), and the obsessive-compulsiveness scale from the Symptom Checklist 90 revised (HR = 0.4, 95% CI 0.12-1.15; P = 0.09). Results showed that post-test trunk flexion, somatization, and obsessive compulsiveness predicted work retention (final trunk flexion HR = 2.5 [95% CI 1.26-4.79; P = 0.01], somatization scale HR = 2.5 [95% CI 1.25-4.93; P = 0.01], and obsessive compulsion HR = 0.2 [95% CI 0.07-0.77; P = 0.02]). Psychosocial and physical factors are associated with work retention for patients with nonspecific LBP. The predictive value of certain constructs may vary with the time when they are assessed and how outcome is operationalized. Further studies are needed to confirm these findings.


Preparation and characterization of monoclonal antibodies specific for GoCodGdCGoCo duplex with high-anti conformation.
Monoclonal antibodies were prepared using a self-complementary oligonucleotide duplex containing cyclonucleosides with the high-anti conformation as an antigen. A competition ELISA assay showed that the monoclonal antibodies specifically recognized high-anti left-handed oligonucleotides but not oligonucleotides with B- or Z-conformation.


Comparative study of protease inhibitors on coagulation abnormalities in canine pancreatitis.
Coagulation abnormalities induced by pancreatitis were studied in 36 dogs. The 12 dogs in group I underwent a duodenotomy alone. The six dogs in groups II, III, IV, and V had pancreatitis induced by bile injection (1 cc/kg) into the pancreatic duct. Twenty minutes after bile-induced pancreatitis, group III was given 1.0 mg/kg aprotinin (trasylol), group IV was given 10 mg/kg S-2441, a new synthetic protease inhibitor, and group V was given 0.5 mg/kg alpha 2-antitrypsin by intravenous infusion over 10 min. Blood was drawn for amylase, protime (PT), partial thromboplastin time (PTT), fibrinogen, and platelets, in addition to markers of hypercoagulation, fibrinopeptide A, and antithrombin III, and markers of fibrinolysis, B beta 15-42 immunoreactive peptide (IP), and alpha 2-antiplasmin at baseline, 1/2, 1, 3, 6, 24, 48, and 72 hr after duodenotomy or bile injection. There was no significant difference in PT, platelets, antithrombin III, and fibrinopeptide A among the five groups. With the induction of pancreatitis (group II), serum amylase was significantly elevated but fibrinogen only became elevated at 24 hr and PTT at 48 hr. The increase in B beta 15-42 IP seen 30 min after induction of pancreatitis and the decrease in alpha 2-antiplasmin were blunted by aprotinin, alpha 1-antitrypsin, and S-2441, but inhibition of the rise in amylase and B beta 15-42 IP only reached significance with S-2441 (P less than 0.05). Pancreatitis-induced fibrinolysis was inhibited by S-2441 suggesting that synthetic protease inhibitors may play a therapeutic role in pancreatitis.


Intracranial hemorrhage in critically ill patients hospitalized for COVID-19.
In this study, we report three cases of spontaneous intracranial hemorrhage in patients who were initially hospitalized at our tertiary care center in Washington, DC with symptoms of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was diagnosed in all three patients, who were critically ill, requiring intubation and ventilatory support. During their protracted hospitalizations, subsequent imaging disclosed intracranial hemorrhages, including intracerebral and subarachnoid hemorrhages, in the context of anticoagulation and coagulopathy. We believe this is related to the tropism of SARS-CoV-2 to the endothelial lining of the cerebral vasculature via their angiotensin-converting enzyme (ACE) II receptors. Given our findings, we advocate heightened vigilance for intracerebral hemorrhage events, and scanning when practicable, in COVID-19 patients which have prolonged ventilatory support and depressed neurologic examinations.


Can statistics cause brain damage?
It is hoped that the comments made above will help contributors to the Journal of Cerebral Blood Flow and Metabolism identify weaknesses in their use of statistics. A little extra care in the presentation of results and adherence to the following guidelines should result in major improvement: (1) Give an explicit description of the type of statistical analysis used. (2) Increase the use of confidence intervals. (3) Use the Bonferroni correction (or other appropriate procedures) in multigroup comparisons. (4) Be aware of the assumptions underlying statistical methods and of weakness in experimental design. However, real benefits will be gained when statistics is viewed as being as important to the experiment as the choice of method for assessing cerebral blood flow itself.