Mental health and substance use disorders at delivery hospitalization and readmissions after delivery discharge.
The objective was to assess mental health and substance use disorders (MSUD) at delivery hospitalization and readmissions after delivery discharge. This is a population-based retrospective cohort study of persons who had a delivery hospitalization during January to September in the 2019 Nationwide Readmissions Database. We calculated 90-day readmission rates for MSUD and non-MSUD, overall and stratified by MSUD status at delivery. We used multivariable logistic regressions to assess the associations of MSUD type, patient, clinical, and hospital factors at delivery with 90-day MSUD readmissions. An estimated 11.8% of the 2,697,605 weighted delivery hospitalizations recorded MSUD diagnoses. The 90-day MSUD and non-MSUD readmission rates were 0.41% and 2.9% among delivery discharges with MSUD diagnoses, compared to 0.047% and 1.9% among delivery discharges without MSUD diagnoses. In multivariable analysis, schizophrenia, bipolar disorder, stimulant-related disorders, depressive disorders, trauma- and stressor-related disorders, alcohol-related disorders, miscellaneous mental and behavioral disorders, and other specified substance-related disorders were significantly associated with increased odds of MSUD readmissions. Three or more co-occurring MSUDs (vs one MSUD), Medicare or Medicaid (vs private) as the primary expected payer, lowest (vs highest) quartile of median household income at residence zip code level, decreasing age, and longer length of stay at delivery were significantly associated with increased odds of MSUD readmissions. Compared to persons without MSUD at delivery, those with MSUD had higher MSUD and non-MSUD 90-day readmission rates. Strategies to address MSUD readmissions can include improved postpartum MSUD follow-up management, expanded Medicaid postpartum coverage, and addressing social determinants of health.


[Lowering the complement-fixing capacity and induction of tolerogenic properties in human globulins by urea treatment].
Deaggregation of human globulin by the treatment with urea solution has been studied. Urea treatment resulted in dose-dependent lowering of complement fixing globulin capacity. The optimal urea dose was 0.12 M for 10 mg/ml of protein. Deaggregated globulin was stable and tolerogenic in the experiments on mice.


Preblastoderm mosaics of mutants of the bithorax-complex.
InDrosophila melanogaster, segmental specification takes place in groups of cells around the blastoderm stage. This segmental specification requires the function of the genes of the bithorax-complex. We have studied preblastoderm mosaics (gynandromorphs) of mutant (bx 3,pbx, Ubx, Ubx 80) and wildtype (heterozygotes for these alleles) cells. The results show a total cell autonomy in the differentiation of both wildtype and homoeotially transformed cells. However, several unexpected phenotypes were found. They are discussed in terms of the function of the bithorax genes and early interactions between mutant and wildtype territories.


Solid pseudo-papillary tumor of the pancreas: Diagnosis by endoscopic ultrasound-guided fine needle aspiration cytology and immunocytochemistry.
Pseudopapillary tumor (SPT) is a rare primary pancreatic neoplasm of uncertain origin and low malignant potential that typically affects young females, mostly in their third decade of life. There are only a few reports on fine needle aspiration (FNA) cytology diagnosis of this neoplasm. We report one such case which was diagnosed based on cytomorphologic and immunocytochemical features on endoscopic ultrasound (EUS) guided FNA smears. A 24-year-old woman presented to the gastroenterology clinic with 3-month history of epigastric pain, anorexia, and weight loss (10 kg over same time period). Abdominal CT revealed a large (13X11 cm) heterogeneous cystic lesion occupying most of the pancreatic body. EUS examination confirmed the presence of a large mixed cystic-solid lesion occupying most of the pancreatic body and neck. EUS-guided FNA smears showed tumor cells in sheets with papillary/pseudo-papillary and acinar formation. The tumor cells had abundant clear and vacuolated cytoplasm and round to oval nuclei with bland chromatin. PAS staining revealed positively stained capillary networks at the core of the papillary/pseudo-papillary structures. In addition, there were PAS positive intra-cytoplasmic and extra-cellular globules which were diastase resistant. Immuno-cytochemical staining on direct smears revealed positive reaction for cyclinD1, vimentin, CD56, beta-catenin, CD10 and progesterone receptor. Thus, this is the example of an extremely rare neoplasm which had a typical clinical and imaging setting, and could be conclusively diagnosed because of characteristic cytomorphological and immunocytochemical features.


The scintigraphic evaluation of myocardial infarction and regional ventricular performance using technetium-99m hexakis (t-butylisonitrile) technetium (I) (TBI): a new myocardial imaging agent.
Technetium-99m hexakis (t-butylisonitrile) technetium (I) (99mTc-TBI) is a new myocardial perfusion imaging agent. To determine its potential in the evaluation of myocardial infarction, 15 patients with suspected or confirmed acute infarction were studied by bedside imaging in the coronary care unit. Good-quality planar scintigrams in multiple projections were obtained in 13 patients. Gated perfusion studies were performed in 14 patients, and for comparison 13 of these were restudied 24-72 h later by standard gated equilibrium blood pool radionuclide ventriculography. Conventional and planar scintigraphic criteria for myocardial infarction (acute or old) agreed in 12 (92%) patients (k = 0.81, p less than 0.05). All the infarctions detected by scintigraphy were associated with electrocardiographic Q-waves. Localization of infarction by the electrocardiogram and scintigraphy exhibited moderate agreement (k = 0.49, p less than 0.1). Regional wall motion analysis by standard radionuclide ventriculography and gated 99mTc-TBI scintigraphy were in complete agreement for 25 (64%) of 39 left ventricular segments (k = 0.35, p less than 0.05). However, in 7 other segments, associated with areas of infarction, regional wall motion abnormalities were noted only on gated 99mTc-TBI scintigraphy. Therefore, 99mTc-TBI scintigraphy can readily provide data on regional myocardial perfusion and wall motion, permitting detection and localization of areas of myocardial infarction. The superior imaging properties, ready availability and low cost of 99mTc point to the considerable potential value of 99mTc-TBI in assessing patients with suspected or confirmed myocardial infarction.


Parental worries and beliefs about abdominal pain.
Solicitous parental responses to stomachaches may perpetuate chronic abdominal pain in children. Discussing these issues in clinical practice is difficult because parents feel misunderstood and blamed for their child's pain. Focusing on parental worries and beliefs that motivate solicitous responses may be better accepted. Our aim was to determine parental fears, worries, and beliefs about their child's chronic abdominal pain that influence parental responses to child's pain. In 2 studies, a large online sample and a smaller community sample consisting of parents with children who have abdominal pain, we developed and evaluated a self-report questionnaire to assess parental Worries and Beliefs about Abdominal Pain (WAP). Principal component analysis identified 4 subscales: "pain is real," "desire for care," "worry about coping," and "exacerbating factors." The WAP is easily understood and possesses adequate initial reliability (Cronbach alpha=0.7-0.9). It shows good initial validity (ie, families who consulted a physician for their child's pain scored higher on the WAP than families who did not consult a physician and the WAP correlates with parental reactions to the child's pain). Discussing parents' fears and worries about their children's chronic abdominal pain may facilitate discussions of social learning of gastrointestinal illness behavior.


Environmental opportunities and challenges of utilizing unactivated calcium peroxide to treat soils co-contaminated with mixed chlorinated organic compounds.
Calcium peroxide (CaO2) has been proven to oxidize various organic pollutants when they exist as a single class of compounds. However, there is a lack of research on the potential of unactivated CaO2 to treat mixed chlorinated organic pollutants in soils. This study examined the potential of CaO2 in treating soils co-contaminated with p-dichlorobenzene (p-DCB) and p-chloromethane cresol (PCMC). The effects of CaO2 dosage and treatment duration on the rate of degradation were investigated. Furthermore, the collateral effects of the treatment on treated soil characteristics were studied. The result showed that unactivated CaO2 could oxidize mixed chlorinated organic compounds in wet soils. More than 69% of the pollutants in the wet soil were mineralized following 21 days of treatment with 3% (w/w) CaO2. The hydroxyl radicals played a significant role in the degradation process among the other decomposition products of hydrogen peroxide. Following the oxidation process, the treated soil pH was increased due to the formation of calcium hydroxide. Soil organic matter, cation exchange capacity, soil organic carbon, total nitrogen, and certain soil enzyme activities of the treated soil were decreased. However, the collateral effects of the system on electrical conductivity, available phosphorus, and particle size distribution of the treated soil were not significant. Likewise, since no significant release of heavy metals was seen in the treated soil matrix, the likelihood of metal ions as co-pollutants after treatment was low. Therefore, CaO2 can be a better alternative for treating industrial sites co-contaminated with chlorinated organic compounds.


Trace elements in children with autism spectrum disorder: A meta-analysis based on case-control studies.
Autism spectrum disorder (ASD) is a common childhood neurodevelopmental disorder that may be related to trace elements. However, reports on the relationship between them are still inconsistent. In this article, we conducted a meta-analysis on this issue. We searched the PubMed, EMBASE, and Cochrane databases as of November 15, 2019. A random-effects model was used, and subgroups of studies were analyzed using samples of different measurements. Twenty-two original articles were identified (18 trace elements, including a total of 1014 children with ASD and 999 healthy controls). In autistic children, the overall levels of barium (Ba), mercury (Hg), lithium (Li), and lead (Pb) were higher. There were significant differences in the levels of copper (Cu) in the hair and serum between autistic children and the control group. The levels of Hg, Li, Pb and selenium (Se) in the hair of autistic children were higher than those of healthy children, while the levels of zinc (Zn) in the blood were lower. Excessive exposure to toxic heavy metals and inadequate intake of essential metal elements may be associated with ASD. Preventing excessive exposure to toxic metals and correcting poor dietary behaviors may be beneficial for the prevention and treatment of the disease.


Predictors of relapse in a bupropion trial for smoking cessation in recently-abstinent alcoholics: preliminary results using an aggregate genetic risk score.
Rates of smoking in the US population have decreased overall, but rates in some groups, including alcoholic smokers, remain high. Many newly sober alcoholics are concerned about their smoking and some attempt to quit. However, quit rates in this population are low. Prior studies suggest risk for relapse in this population may be genetically influenced and that genetic factors may moderate response to treatment. IN THIS EXPLORATORY STUDY, WE HAD TWO SPECIFIC AIMS: (1) to investigate associations between genetic risk and outcome; (2) to investigate whether genetic risk moderates the efficacy of a medication intervention. Data are from a subsample of 90 participants from a clinical trial of smoking cessation treatment for smokers with between 2 and 12 months of alcohol abstinence. Subjects were randomly assigned to bupropion or placebo. All subjects received counseling and nicotine patches. To examine the possibility that bupropion may have been efficacious in participants with a specific genetic profile (ie, a pharmacogenetic approach), an aggregate genetic risk score was created by combining risk genotypes previously identified in bupropion treatment studies. Although medication efficacy was not moderated by the aggregate genetic risk score, there was an interaction between nicotine dependence and genetic risk in predicting smoking abstinence rates at the end of treatment (10 weeks). Results suggest an aggregate genetic risk score approach may have utility in treatment trials of alcoholics who smoke. Additionally, these findings suggest a strategy for understanding and interpreting conflicting results for single genetic markers examined as moderators of smoking cessation treatment.


Bilateral Femoral Neck Stress Fracture in an Obese Middle-Aged Female With Osteomalacia and Coxa-Vara Managed by Simultaneous Bilateral Total Hip Arthroplasty.
Femoral neck stress fractures in middle-aged individuals are usually associated with underlying metabolic bone disease. There is increased abnormal loading on femoral neck with associated coxa-vara and obesity in a female. Bilateral presentation of such fractures is rarely reported. Their management poses significant challenges. We present a case of bilateral femoral neck stress fracture in a 58-year-old obese housewife with compression type of the left hip fracture and tension type of the right hip fracture with non-union following an operated femoral neck stress fracture. She presented two months from the onset of symptoms and was treated with simultaneous bilateral total hip replacement for the management of her painful hips. Follow-up at 18 months revealed excellent outcome and return to independent painless daily routine activity. This report highlights the importance of early recognition of femoral neck stress fracture and challenges in the management of their late presentation. Total hip arthroplasty allows early mobilization with a favorable functional outcome.


Deletion mapping of regulatory elements for GATA3 in T cells reveals a distal enhancer involved in allergic diseases.
GATA3 is essential for T cell differentiation and is surrounded by genome-wide association study (GWAS) hits for immune traits. Interpretation of these GWAS hits is challenging because gene expression quantitative trait locus (eQTL) studies lack power to detect variants with small effects on gene expression in specific cell types and the genome region containing GATA3 contains dozens of potential regulatory sequences. To map regulatory sequences for GATA3, we performed a high-throughput tiling deletion screen of a 2 Mb genome region in Jurkat T cells. This revealed 23 candidate regulatory sequences, all but one of which is within the same topological-associating domain (TAD) as GATA3. We then performed a lower-throughput deletion screen to precisely map regulatory sequences in primary T helper 2 (Th2) cells. We tested 25 sequences with ∼100 bp deletions and validated five of the strongest hits with independent deletion experiments. Additionally, we fine-mapped GWAS hits for allergic diseases in a distal regulatory element, 1 Mb downstream of GATA3, and identified 14 candidate causal variants. Small deletions spanning the candidate variant rs725861 decreased GATA3 levels in Th2 cells, and luciferase reporter assays showed regulatory differences between its two alleles, suggesting a causal mechanism for this variant in allergic diseases. Our study demonstrates the power of integrating GWAS signals with deletion mapping and identifies critical regulatory sequences for GATA3.


A pathological study following bronchial artery embolization for haemoptysis in cystic fibrosis.
A detailed post-mortem study is reported on an adult with cystic fibrosis who died in respiratory failure three weeks after selective bronchial artery embolization with gelatin sponge to treat severe haemoptysis. Bronchial arteriography during the procedure showed complete occlusion of the vessel supplying the righ upper lobe and following this the bleeding stopped. However, post-mortem angiography of the same vessel demonstrated disappearance of much of the injected material with contrast bypassing the remaining gelatin to fill the peripheral bronchial arterial bed. This report therefore adds pathological evidence to previous clinical reports which have suggested that this procedure may not produce permanent occlusion of the embolised bronchial artery.


Qualitative and Quantitative Comparison of Hippocampal Volumetric Software Applications: Do All Roads Lead to Rome?
Brain volumetric software is increasingly suggested for clinical routine. The present study quantifies the agreement across different software applications. Ten cases with and ten gender- and age-adjusted healthy controls without hippocampal atrophy (median age: 70; 25-75% range: 64-77 years and 74; 66-78 years) were retrospectively selected from a previously published cohort of Alzheimer's dementia patients and normal ageing controls. Hippocampal volumes were computed based on 3 Tesla T1-MPRAGE-sequences with FreeSurfer (FS), Statistical-Parametric-Mapping (SPM; Neuromorphometrics and Hammers atlases), Geodesic-Information-Flows (GIF), Similarity-and-Truth-Estimation-for-Propagated-Segmentations (STEPS), and Quantib™. MTA (medial temporal lobe atrophy) scores were manually rated. Volumetric measures of each individual were compared against the mean of all applications with intraclass correlation coefficients (ICC) and Bland-Altman plots. Comparing against the mean of all methods, moderate to low agreement was present considering categorization of hippocampal volumes into quartiles. ICCs ranged noticeably between applications (left hippocampus (LH): from 0.42 (STEPS) to 0.88 (FS); right hippocampus (RH): from 0.36 (Quantib™) to 0.86 (FS). Mean differences between individual methods and the mean of all methods [mm3] were considerable (LH: FS -209, SPM-Neuromorphometrics -820; SPM-Hammers -1474; Quantib™ -680; GIF 891; STEPS 2218; RH: FS -232, SPM-Neuromorphometrics -745; SPM-Hammers -1547; Quantib™ -723; GIF 982; STEPS 2188). In this clinically relevant sample size with large spread in data ranging from normal aging to severe atrophy, hippocampal volumes derived by well-accepted applications were quantitatively different. Thus, interchangeable use is not recommended.


Population Pharmacokinetics of Sunitinib and its Active Metabolite SU012662 in Pediatric Patients with Gastrointestinal Stromal Tumors or Other Solid Tumors.
Population pharmacokinetic analysis explored the pharmacokinetics of sunitinib and its primary active metabolite, SU012662, in children and evaluated the sunitinib dose(s) that produce comparable plasma exposures to adults receiving the approved daily dose. Data were from 65 children with gastrointestinal stromal tumors (GIST) or solid tumors. Pharmacokinetic models of sunitinib and SU012662 were developed using a systematic multi-step approach employing nonlinear mixed-effects modeling. The effect of predefined covariates on pharmacokinetic parameters was assessed. Final models were validated using visual predictive check and statistical techniques. The final dataset comprised 439 sunitinib and 417 SU012662 post-baseline plasma observations. Base models were characterized by two-compartment models with first-order absorption and lag time. Body surface area (BSA) was the only covariate that affected (P < 0.001) pharmacokinetic parameters for sunitinib and SU012662 and was incorporated into the final models. Bootstrap results indicated that the final models represented the final dataset adequately. Based on the final models, a sunitinib dose of ~ 20mg/m2/day in children with GIST aged 6-17 years would be expected to lead to similar total plasma exposures of sunitinib and SU012661 as a dose of 50 mg/day in an adult with GIST on schedule 4/2. In children with GIST or solid tumors receiving sunitinib, population pharmacokinetic analysis identified BSA as the only covariate that affected pharmacokinetic parameters and predicted a dose of ~ 20 mg/m2/day as achieving equivalent exposure to 50 mg/day in adults with GIST on schedule 4/2. ClinicalTrials.gov identifiers (date registered): NCT01396148 (July 2011); NCT01462695 (October 2011); NCT00387920 (October 2006).


Independent ATPase activity of Hsp90 subunits creates a flexible assembly platform.
The ATPase activity of the molecular chaperone Hsp90 is essential for its function in the assembly of client proteins. To understand the mechanism of human Hsp90, we have carried out a detailed kinetic analysis of ATP binding, hydrolysis and product release. ATP binds rapidly in a two-step process involving the formation of a diffusion-collision complex followed by a conformational change. The rate-determining step was shown to be ATP hydrolysis and not subsequent ADP dissociation. There was no evidence from any of the biophysical measurements for cooperativity in either nucleotide binding or hydrolysis for the dimeric protein. A monomeric fragment, lacking the C-terminal dimerisation domain, showed no dependence on protein concentration and, therefore, subunit association for activity. The thermodynamic linkage between client protein binding and nucleotide affinity revealed ATP bound Hsp90 has a higher affinity for client proteins than the ADP bound form. The kinetics are consistent with independent Michaelis-Menten catalysis in each subunit of the Hsp90 dimer. We propose that Hsp90 functions in an open-ring configuration for client protein activation.


A comparison of robotic mesh repair techniques for primary uncomplicated midline ventral hernias and analysis of risk factors associated with postoperative complications.
We aim to compare short-term outcomes of robotic intraperitoneal onlay (rIPOM), transabdominal preperitoneal (rTAPP) and retromuscular (rRM) repair for uncomplicated midline primary ventral hernias (PVH) and determine risk factors associated with postoperative complications. The three groups were compared in terms of pre-, intra-, and post-operative variables. Postoperative complications were assessed using previously validated classifications. Univariate analyses were conducted to determine which variables influence postoperative complications (up to 90 days), followed by a multivariate regression analysis revealing statistically important risk factors. A total of 269 patients who underwent robotic PVH repair patients were grouped as rIPOM (n = 90), rTAPP (n = 108), and rRM (n = 71). rRM repair allowed for the use of larger-sized meshes for larger defects; however, it was associated with higher-grade complications. rTAPP repair resulted in the lowest morbidity and offered the highest mesh-to-defect ratio for smaller-sized hernias. Operative time for the rRM group was longer. The rIPOM group had a higher morbidity, likely due to higher frequency of minor complications, as compared to rTAPP and rRM groups. Multivariate regression analysis revealed that coronary artery disease, absence of defect closure, intraperitoneally placed mesh, and skin-to-skin time (minutes) were significantly associated with postoperative complications. Robotic PVHR contributes multiple techniques to a surgeon's armamentarium, such as IPOM, TAPP, and RM mesh placements. Patient characteristics as well as the potential consequences of each technique need to be taken into consideration when deciding the appropriate approach for the repair of primary uncomplicated midline ventral hernias.


Cilostazol novel neuroprotective mechanism against rotenone-induced Parkinson's disease in rats: Correlation between Nrf2 and HMGB1/TLR4/PI3K/Akt/mTOR signaling.
Neuroinflammation induced by activation of the high mobility group box 1/ toll-like receptor 4 (HMGB1/TLR4) axis is one of the principal mechanisms involved in dopaminergic neuronal loss in Parkinson's disease (PD), and its activation exacerbates oxidative stress augmenting neurodegeneration. This study investigated the novel neuroprotective effect of cilostazol on rotenone-intoxicated rats focusing on the HMGB1/TLR4 axis, erythroid-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1), and phosphoinositide 3-kinase (PI3K)/Protein kinase B (Akt)/the mammalian target of rapamycin (mTOR) pathway. The aim is extended to correlate the Nrf2 expression with all assessed parameters as promising therapeutic targets for neuroprotection. Our experiment was designed as follows: vehicle group, cilostazol group, rotenone group (1.5 mg/kg, s.c), and the rotenone pretreated with cilostazol (50 mg/kg, p.o.) group. Eleven rotenone injections were injected day after day, while cilostazol was administered daily for 21 days. Cilostazol significantly improved the neurobehavioral analysis, the histopathological examination, and dopamine levels. Moreover, the immunoreactivity of tyrosine hydroxylase (TH) in substantia nigra pars compacta (SNpc) enhanced. These effects were associated with enhancement of the antioxidant expression of Nrf2 and HO-1 by 1.01 and 1.08-fold, respectively, and repression of HMGB1/TLR4 pathway by 50.2 % and 39.3 %, respectively. Upregulation of the neuro-survival PI3K and Akt expression by 2.26 and 2.69-fold, respectively, and readjusting mTOR overexpression. Cilostazol exerts a novel neuroprotective strategy against rotenone-induced neurodegeneration via activation of Nrf2/HO-1, suppression of HMGB1/TLR4 axis, upregulation of PI3K/Akt besides mTOR inhibition that compels more investigations with different PD models to clarify its precise role.


Association between hashimoto thyroiditis and differentiated thyroid cancer: A single-center experience.
Hashimoto's thyroiditis is the most common cause of hypothyroidism in the iodine-sufficient areas of the world. Differentiated thyroid cancer is the most common thyroid cancer subtype, accounting for more than 95% of cases, and it is considered a tumor with a good prognosis, although a certain number of patients experience a poor clinical outcome. Hashimoto's thyroiditis has been found to coexist with differentiated thyroid cancer in surgical specimens, but the relationship between these two entities has not yet been clarified. Our study aims to analyze the relationship between these two diseases, highlighting the incidence of histological diagnosis of Hashimoto thyroiditis in differentiated thyroid cancer patients, and assess how this autoimmune disorder influences the risk of structural disease recurrence and recurrence rate.


Lipoic acid content of Escherichia coli and other microorganisms.
A mutant strain of Escherichia coli K-12 requiring lipoic acid. W1485lip 2 (ATCC 25645), was used to develop a turbidimetric assay for lipoic acid and a polarographic assay based on the oxidation of pyruvate by suspensions of lipoic acid-deficient organisms. The turbidmetric assay was more sensitive with a working range equivalent to 0.2-2.0 ng of DL-alpha-lipoic acid compared with 5-50 ng for the polarographic method. The mutant responded equally to racemic mixtures of alpha-lipoic acid, beta-lipoic acid and dihydrolipoic acid but gave little response to lipoamide, and other derivatives without prior hydrolysis; 8-methyllipoic acid was a competitive inhibitor of the response to lipoic acid. A high specificity of the mutant for the natural steroisomer was indicated by the fact that (+)-alpha-lipoic acid had twice the activity of the racemic mixture. Escherichia coli K12 contained less than 0.05 ng of free (+)-alpha-lipoic acid per mg dry weight but, depending on the growth substrate, the equivalent of between 13 and 47 ng of (+)-alpha-lipoic acid per mg dry weight after acid extraction. There was a strong correlation between the lipoic acid content and the sum of the specific activities for the pyruvate and alpha-ketoglutarate dehydrogenase complexes. Experiments with washed suspensions of Escherichia coli showed only small increases in lipoic acid content (18%) when incubated with pyruvate, cysteine and methionine. When supplied with exogenous lipoic acid the mutant, W1485lip2, accumulated very little more than was demanded by its metabolism. The lipoic acid contents of several organisms were measured and correlated with their metabolism.


Effect of an oral contraceptive in primary dysmenorrhea--changes in uterine activity and reactivity to agonists.
Mechanisms for the therapeutic effect of oral contraceptives in dysmenorrhea were studied by recording intrauterine pressure on the first day of menstrual bleeding in women with moderate to severe symptoms and after three weeks of oral contraceptive therapy (150 micrograms levonorgestrel + 30 micrograms ethinyl estradiol, daily). Spontaneous uterine activity and reactivity to intravenous injections of vasopressin (6 pmol/kg body weight; n = 8) or prostaglandin F2 alpha (12 nmol/kg body weight; n = 9) at the two sessions were compared. During the first recording when all women had dysmenorrhea, the uterine activity and reactivity to both agonists were pronounced. After therapy, when the women felt essentially no pain, a statistically significant decrease in spontaneous uterine activity in terms of total pressure area, frequency and amplitude of contractions was observed. The agonist injections induced less pain at the second recording, although the magnitude of responses, superimposed on the much smaller uterine activity at this time, were not significantly different from those at the first recording during dysmenorrhea. The mechanism of pain relief by oral contraception in dysmenorrhea could be a lesser impact of the decreased contractile activity on uterine blood flow, abolishing the local ischemia. A reduced uterine reactivity to agonists might also to some extent contribute to the therapeutic effect.


Global sagittal alignment of the spine, pelvis, lower limb after vertebral compression fracture and its effect on quality of life.
Vertebral compression fractures (VCFs) are the most common among all osteoporotic fractures. The body may compensate to the kyphosis from vertebral compression fractures with lordosis of the adjacent spinal segments, rotation of the pelvis, knee flexion and ankle dorsiflexion. However, the detailed degree of body compensation, especially the lower limb, remains uncertain. Herein, the aim of this study is to investigate the values of global sagittal alignments (GSA) parameters, including the spine, pelvis and lower limbs, in patients with and without VCFs, as well as to evaluate the effect of VCFs on various quality of life (QoL) parameters. A cross-sectional study was conducted from May 2015 to June 2018. A total of 142 patients with VCFs aged over 60 years old and 108 age-matched asymptomatic controls were recruited. Whole body sagittal alignment including thoracic kyphosis (TK), lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), sagittal vertical axis (SVA), T1-pelvic angle (TPA), knee-flex angle (KA) and ankle-flex angle (AA) were measured. In addition, lower back pain and quality of life were assessed using self-reported questionnaires. Compared to asymptomatic controls, patients with VCF showed significantly greater TK (33.4o ± 16.4o vs 28.4o ± 11.4o; p < 0.01), PT (25.4o ± 10.5o vs 16.6o ± 8.9o; p < 0.001), PI (54.6o ± 11.8o vs 45.8o ± 12.0o; p < 0.001), SVA (49.1 mm ± 39.6 mm vs 31.5 mm ± 29.3 mm; p < 0.01), and TPA (28.6o ± 10.8o vs 14.8o ± 8.6o; p < 0.001). Whereas for lower limb alignment, patients with VCF showed significantly higher KA (10.1o ± 7.8o vs 6.0o ± 6.4o; p < 0.001) and AA (7.0o ± 3.9o vs 4.8o ± 3.6o; p < 0.001) than controls. The number of VCF significantly correlated with lower limb alignments (KA and AA) and global sagittal balance (TPA). VCF patients showed poorer quality of life assessment scores in terms of SF-12 (30.0 ± 8.3 vs 72.4 ± 16.9; p < 0.001), ODI (37.8 ± 24.0 vs 18.7 ± 16.6; p < 0.001) and VAS (3.8 ± 2.8 vs 1.9 ± 2.2; p < 0.001). This is the first study to illustrate the abnormal lower limb alignment exhibited in patients with VCF. Patients with VCF showed an overall worse global sagittal alignment and decreased quality of life. Poorer global sagittal alignment of VCF patients also imply worse quality of life and more severe VCF.


Local synergies and antagonisms between meteorological factors and air pollution: A 15-year comprehensive study in the Sydney region.
Associated with rapid urbanization and escalation of bushfire events, Sydney has experienced significant air quality degradation in the XXI century. In this study, we present a 15-year retrospective analysis on the influence of individual meteorological factors on major air pollutants (NO2, O3, PM10 and PM2.5) at 14 different sites in Greater Sydney and Illawarra. By applying a newly developed "zooming in" approach to long-term ground-based data, we disclose general, seasonal, daily and hourly patterns while increasing the level of spatial associativity. We provide evidence on the pivotal role played by urbanization, sprawling dynamics, global warming and bushfires on local meteorology and air pollution. We strike associations between temperature and O3, both as average trends and extremes, on account of increasing heat island effects. The role of wind in a coastal-basin environment, influenced by a vast desert biome inland, is investigated. A steady trend towards stagnation is outlined, boosted by enhanced urban roughness and intensified heat island circulation. Relative humidity is also crucial in the modulation between NO2 and O3. With a sharp tendency towards drier and hotter microclimates, NO2 levels dropped by approximately 50% over the years at all locations, while O3's median levels almost doubled in the last 10 years. Further, O3 and PMs shifted towards more frequent extreme events, strongly associated with the exacerbation of bushfire events. Such results suggest an urgent need to prioritize emission control, building air tightness improvement and urban heat mitigation, towards a future-proof governance in Sydney and similar regions in the world.


Survival and impact of clinical prognostic factors in surgically treated metastatic renal cell carcinoma.
The survival impact of metastasectomy for metastatic renal cell carcinoma (mRCC) is still an active research field, particularly in the multimodal/targeted therapy era. To determine the survival impact of clinical prognostic factors and their application to stratification of patients according to their prognosis so clinicians may be aided in their management of mRCC. Retrospective, bi-institutional cohort study of 109 consecutive patients (71 male and 38 female; median age: 62 yr (range: 25-82 yr) with renal cell carcinoma (RCC) who underwent partial or radical nephrectomy and at least one metastasectomy for mRCC. Metastasis resection from various anatomic sites with the aim of completely removing detected lesions. Univariable and multivariable Cox regression models were used to analyse the impact of clinical prognostic factors on cancer-specific survival (CSS). Kaplan-Meier analysis with the log-rank test was used to compare CSS. Receiver operating characteristic (ROC) analysis was performed to test accuracy of prognostic groups. The α error for statistical significance was set at 0.05. Multivariable analysis revealed that primary tumour T stage ≥ 3 (hazard ratio [HR]: 2.8; p<0.01), primary tumour Fuhrman grade ≥ 3 (HR: 2.3; p<0.03), nonpulmonary metastases (HR: 3.1; p<0.03), disease-free interval ≤ 12 mo (HR: 2.3; p<0.058), and multiorgan metastases (HR: 2.5; p<0.04) were independent pretreatment prognostic factors. Leuven-Udine (LU) prognostic groups based on these covariates were created and analysed with Kaplan-Meier and log-rank tests. The 2- and 5-yr CSS were significantly different; the respective group A CSS rates were 95.8% and 83.1%; group B, 89.9% and 56.4%; group C, 65.6% and 32.6%; and group D, 24.7% and 0% (p<0.0001). ROC analysis on the accuracy of prognostic grouping revealed respective areas under the curve of 0.87 and 0.88 at 2 and 5 yr. Main limitations to present study are the retrospective design and the presence of different metastasis sites. LU prognostic groups could be considered an accurate clinical tool to stratify patients according to prognosis and aid clinicians in the management of mRCC.


Establishing minimal clinically important difference for the UCLA and ASES scores after rotator cuff repair.
Minimal clinically important difference (MCID) is a vital tool in the analysis of clinical results. It allows the determination of clinical relevance of statistical data. Our hypothesis was that specific differences between preoperative and postoperative scores would be able to accurately predict patient perception of improvement and satisfaction as reflected by anchor and distribution-based questions. Retrospective cohort with patients that underwent rotator cuff repair. We evaluated the University of California at Los Angeles Shoulder Rating Scale (UCLA) and the American Shoulder and Elbow Surgeons Assessment Form (ASES) before and 12-months after surgery. Anchor-based, distribution-based and minimum detectable change (MDC) approaches were utilized. We evaluated 289 shoulders. The MCID for the UCLA scale was 4.5 points using the anchor method, 2.5 by the distribution method and 3.6 by MDC. Patients with a baseline score>20 presented a lower MCID (1.5, 1.1 and 1.7, respectively). For the ASES score, the MCID was 6.1 by the anchor method, 10.5 based on the distribution method and 26.3 by MDC. In the group of patients above the 60 point cutoff, the obtained values were 2.4, 4.9 and 13.6, respectively. The mean MCID value for the UCLA shoulder score is 3.5 points, ranging from 2.5 points (distribution method) to 4.5 points (anchor method). The mean MCID value for the ASES score was 15.2 points, ranging from 6.1 (anchor method) to 26.3 (MDC). Patients groups presenting with higher preoperative scores showed lower MCID values. This fact needs to be considered in postoperative comparisons between treatment groups. Basic Science Study, Validation of Outcomes Instruments/Classification Systems.


The principal islet of the Coho salmon (Oncorhyncus kisutch) contains the BB isoenzyme of creatine kinase.
The importance of creatine kinase (E.C. 184.108.40.206) in endocrine tissues has been generally overlooked. Using a specific radiometric assay, we have demonstrated the existence of CK in the Brockmann body (principal islet) of the Coho salmon. We have purified this protein from insular tissue and concurrently purified CK from brain and muscle of the salmon. Purification characteristics, immunological cross-reactivity, and N-terminal sequence analysis have demonstrated that the predominant cytosolic CK from the Brockmann body is indistinguishable from the BB (brain) isoenzyme. Immunocytochemical studies indicated that the enzyme resides in the endocrine parenchyma. Phosphocreatine may serve as a reservoir of energy in the islet and augment its capacity to secrete hormones. The induction of CK-BB in the islet by other hormones could influence the secretion of insular hormones. Interorgan flux of the substrate creatine may be an undescribed mechanism of physiological regulation.


Nanoval Technology-An Intermediate Process between Meltblown and Spunbond.
The idea of "Nanoval technology" origins in the metal injection molding for gas atomization of metal powders and the knowledge of spunbond technologies for the creation of thermoplastic nonwovens using the benefits of both techniques. In this study, we evaluated processing limits experimentally for the spinning of different types of polypropylene, further standard polymers, and polyphenylene sulfide, marked by defect-free fiber creation. A numerical simulation study of the turbulent air flow as well as filament motion in the process visualized that the turnover from uniaxial flow (initial stretching caused by the high air velocity directed at the spinning die) to turbulent viscoelastic behavior occurs significantly earlier than in the melt-blown process. Modeling of the whole process showed that additional guide plates below the spinneret reduce the turbulent air flow significantly by regulating the inflow of secondary process air. The corresponding melt flow index of processible polymer grades varied between 35 g·10min-1 up to 1200 g·10min-1 and thus covering the range of extrusion-type, spunbond-type, yarn-type, and meltblown-type polymers. Hence, mean fiber diameters were adjustable for PP between 0.8 and 39.3 μm without changing components of the process setup. This implies that the Nanoval process enables the flexibility to produce fiber diameters in the typical range achievable by the standard meltblown process (~1-7 μm) as well as in the coarseness of spunbond nonwovens (15-30 μm) and, moreover, operates in the gap between them.


Proton Therapy for Prostate Cancer: Challenges and Opportunities.
The dosimetric advantages of proton therapy (PT) treatment plans are demonstrably superior to photon-based external beam radiotherapy (EBRT) for localized prostate cancer, but the reported clinical outcomes are similar. This may be due to inadequate dose prescription, especially in high-risk disease, as indicated by the ASCENDE-RT trial. Alternatively, the lack of clinical benefits with PT may be attributable to improper dose delivery, mainly due to geometric and dosimetric uncertainties during treatment planning, as well as delivery procedures that compromise the dose conformity of treatments. Advanced high-precision PT technologies, and treatment planning and beam delivery techniques are being developed to address these uncertainties. For instance, external magnetic resonance imaging (MRI)-guided patient setup rooms are being developed to improve the accuracy of patient positioning for treatment. In-room MRI-guided patient positioning systems are also being investigated to improve the geometric accuracy of PT. Soon, high-dose rate beam delivery systems will shorten beam delivery time to within one breath hold, minimizing the effects of organ motion and patient movements. Dual-energy photon-counting computed tomography and high-resolution Monte Carlo-based treatment planning systems are available to minimize uncertainties in dose planning calculations. Advanced in-room treatment verification tools such as prompt gamma detector systems will be used to verify the depth of PT. Clinical implementation of these new technologies is expected to improve the accuracy and dose conformity of PT in the treatment of localized prostate cancers, and lead to better clinical outcomes. Improvement in dose conformity may also facilitate dose escalation, improving local control and implementation of hypofractionation treatment schemes to improve patient throughput and make PT more cost effective.


Postnatal changes in the nicotinic acetylcholine receptor subunits in rat masseter muscle.
No published study on synaptogenesis in masseter muscle has focused on the shift of nicotinic acetylcholine receptors (nAChRs) from the embryonic type (alpha(2)-, beta-, gamma- and delta-subunits) to the adult-type (alpha(2)-, beta-, epsilon- and delta-subunits) and the elimination of nAChRs outside the neuromuscular junction. To identify the time course of the nAChR transitions in rat masseter muscle between 1 and 63 days of age, the expression of delta-, epsilon- and gamma-subunit mRNAs was analysed by competitive polymerase chain reaction in combination with reverse transcription. The expression of the delta-subunit was high between 1 and 7 days of age, then decreased by 95% (P<0.0001) between 7 and 28 days, suggesting that the nAChR elimination occurs during this period. The quantity of the epsilon-subunit increased by approximately 600% (P<0.0001) between 1 and 21 days of age, whereas the quantity of the gamma-subunit decreased by 85% (P<0.0001) during the same period. This result indicates that the nAChR type shift is terminated at 21 days of age. The feeding behaviour of the rats inevitably changed from suckling to biting after 19 days of age, because they were weaned at that age. As the nAChR type shift was terminated soon after weaning, the termination could be related to the change in feeding behaviour. However, it might also be the case that nAChR elimination is not directly related to the change in feeding behaviour, as the elimination continued at the same rate for 9 days after weaning (from 19 to 28 days of age).


Neutralizing antibody response to Japanese encephalitis inactivated mouse brain vaccine among laboratory personnel.
Among vaccinees given two doses of JE Nakayama strain liquid vaccine, 41.8% had significant neutralizing (N) antibody response to the P20778 strain and 48.6% to the Japanese Nakayama strain. Among vaccinees who received three doses of the freeze-dried vaccine, the proportion of positive reactors was 53.8% when the sera were tested with the P20778 strain and 47.4% with the Nakayama strain. A fairly large proportion of those vaccinees who had responded positively to the latter vaccine were found to have lost detectable N antibodies to the P20778 strain and a smaller proportion to the Nakayama strain 13 to 17 months after the third dose of vaccine. Following the administration of a booster dose of the vaccine after this time interval, 65.2% and 56.5% of vaccinees responded positively to the P20778 strain and the Nakayama strain, respectively. The differences between the proportion of positive reactors to the two strains were not significant either for the liquid vaccine or the freeze-dried vaccine. An important finding was the priming effect of infection with West Nile (WN) virus before vaccination. Those vaccinees who had N antibody to WN virus before vaccination had a significantly higher N antibody response to the P20778 strain of JE virus than those who had no detectable antibody to WN virus. These findings indicate that the JE Nakayama strain vaccine would be efficacious in India, particularly in view of the widespread prevalence of WN virus infection.


A review on preparation and chemical analysis of postbiotics from lactic acid bacteria.
Postbiotics may be defined as soluble metabolites released by food-grade microorganisms during the growth and fermentation in complex microbiological culture, food or gut. It is rich in high and low molecular weight biologically active metabolites. There are still gaps concerning these substances, mainly how to use them for food applications. Although the most recent work on preparation and application of postbiotics from several probiotics are very encouraging, the suitability of postbiotics to combat microorganisms that deal with food safety should be tested mainly by analyzing the chemical composition and conducting antagonistic tests. Consequently, foods can effectively benefit from an identified postbiotic with a defined effect. This review approached the recent advances in relation to the preparation of postbiotics from lactic acid bacteria. The function of different instrumental analysis techniques and factors affecting the chemical composition of postbiotics were also comprehensively reviewed.


Kinome Reprogramming Is a Targetable Vulnerability in ESR1 Fusion-Driven Breast Cancer.
Transcriptionally active ESR1 fusions (ESR1-TAF) are a potent cause of breast cancer endocrine therapy (ET) resistance. ESR1-TAFs are not directly druggable because the C-terminal estrogen/anti-estrogen-binding domain is replaced with translocated in-frame partner gene sequences that confer constitutive transactivation. To discover alternative treatments, a mass spectrometry (MS)-based kinase inhibitor pulldown assay (KIPA) was deployed to identify druggable kinases that are upregulated by diverse ESR1-TAFs. Subsequent explorations of drug sensitivity validated RET kinase as a common therapeutic vulnerability despite remarkable ESR1-TAF C-terminal sequence and structural diversity. Organoids and xenografts from a pan-ET-resistant patient-derived xenograft model that harbors the ESR1-e6>YAP1 TAF were concordantly inhibited by the selective RET inhibitor pralsetinib to a similar extent as the CDK4/6 inhibitor palbociclib. Together, these findings provide preclinical rationale for clinical evaluation of RET inhibition for the treatment of ESR1-TAF-driven ET-resistant breast cancer. Kinome analysis of ESR1 translocated and mutated breast tumors using drug bead-based mass spectrometry followed by drug-sensitivity studies nominates RET as a therapeutic target. See related commentary by Wu and Subbiah, p. 3159.


Bis(2-amino-3-carb-oxy-pyridinium) sulfate trihydrate.
In the title compound, 2C(6)H(7)N(2)O(2) (+)·SO(4) (2-)·3H(2)O, there are two independent cations which are connected into N-H⋯O hydrogen-bonded dimers. In the crystal, O-H⋯O hydrogen-bonded sulfate-water sheets run parallel to (001) and are linked into a three-dimensional network via inter-molecular N-H⋯O and O-H⋯O hydrogen bonds through the 2-amino-nicotinium dimers. Further stabilization is provided by weak inter-molecular C-H⋯O hydrogen bonds. R(4) (3)(10) and R(2) (2)(8) graph-set rings are observed. The crystal studied was an inversion twin with refined components of 0.45 (6) and 0.55 (6).


Fermentation of Coffea canephora inoculated with yeasts: Microbiological, chemical, and sensory characteristics.
This work aimed to evaluate Coffea canephora's microbiological, chemical, and sensory characteristics at 300 and 600 m elevation plantations processed by the natural method inoculated with yeasts. The coffee was spread on suspended terraces and sprayed with approximately 107 cfu/mL of Meyerozyma caribbica CCMA 1738 or Pichia kluyveri CCMA 1743, separately. Cherries containing bark and parchment were collected during fermentation for microbial groups counting, qPCR, quantification of organic acids, and sugars (HPLC). Volatile compounds (GC-MS) and sensory analyses, cupping test with expert coffee tasters and triangular test with consumers, were performed on roasted coffee beans. The inoculated yeasts persisted during the entire fermentation process. M. caribbica reduced the filamentous fungal population by 63% and 90% in the 300- and 600-m coffees, respectively. The 300-m coffee fruits showed higher concentrations of organic acids in all fermentation times when compared to the 600-m reaching out to 8 times more. Twenty-four volatile compounds were identified in the roasted coffee beans, with the predominance of pyrazines. The 600-m coffee inoculated with M. caribbica showed an increase of more than one point in the score given by certified tasters. Consumers noticed the M. caribbica inoculation in the 300- and 600-m-elevation coffees. M. caribbica is a promising starter culture for Conilon coffee with the potential to increase the beverage quality.


Experimental and numerical investigation of the effect of ultrasound on the growth kinetics of zeolite A.
Ultrasound is a promising technology for the improvement of zeolite production, due to its beneficial effects on mass transfer and nucleation. However, a broad understanding of the sonication parameters that influence the growth of zeolites most is still lacking. In the present work, zeolite A was synthesized and the kinetic model of Gualtieri was used to obtain information about the crystallization parameters. The effect of the sonication power and duration on the relative crystallinity and particle size distribution were investigated using a Langevin-type transducer operating at 40 kHz. The experimental data shows that ultrasound has a significant effect on the nucleation and growth. With that, a reduction of up to 40 % of the initial synthesis time can be achieved. Additionally, a narrower particle size distribution is achieved when ultrasound is used during the zeolite A synthesis.


Single-Port Robotic Radical Cystectomy with Intracorporeal Bowel Diversion: Initial Experience and Review of Surgical Outcomes.
Introduction and Objective: Scant literature is available on surgical outcomes of radical cystectomies on the new single-port (SP) system. This study compares short-term outcomes in patients undergoing radical cystectomy with those undergoing intracorporeal urinary diversion (ICUD) on the multiport (MP) vs SP platform. Methods: This institutional review board approved study used a prospective cystectomy database and nonparametric testing including chi-squared, Mann-Whitney U, and Fisher exact tests to analyze all variables stratified by surgical approach. Results: Thirty-four patients underwent radical cystectomy with ICUD from September 1, 2019, to February 8, 2021. Twenty patients were in the MP cohort, whereas 14 were in the SP group. Table 1 presents the demographics of both groups and shows no statistically significant differences. Intra- and postoperative as well as pathology data are given in Table 2. Patients in the SP group had less narcotic use (MP: 25 morphine milligram equivalent [MME] vs SP: 11.5 MME, p = 0.047) and shorter return of bowel function (MP: 3 days vs SP: 2 days, p = 0.032). Operative times were similar between both groups despite having fewer patients undergoing ileal conduit (MP: 85% vs SP: 50%, p = 0.027) in the SP group. In Table 3, we list the early short-term postoperative follow-up data for each group that showed no significant differences between the two groups with an average follow-up of 4.9 months for MP and 4.4 months for SP. Conclusions: Our initial experience with SP robotic cystectomy and ICUD appears to be safe and an effective alternative to MP cystectomies. A learning curve was involved but the overall transition from MP to SP was smooth. Operative times were similar despite fewer patients undergoing ileal diversion, shorter return of bowel function, and less narcotic use in the SP group. Further studies including longer follow-ups with multi-institutional data are underway.


ARE-mRNA degradation requires the 5'-3' decay pathway.
As an important mode of suppressing gene expression, messenger RNAs containing an AU-rich element (ARE) in the 3' untranslated region are rapidly degraded in the cytoplasm. ARE-mediated mRNA decay (AMD) is initiated by deadenylation, and in vitro studies have indicated that subsequent degradation occurs in the 3'-5' direction through a complex of exonucleases termed the exosome. An alternative pathway of mRNA degradation occurs at processing bodies, cytoplasmic foci that contain decapping enzymes, the 5'-3' exonuclease Xrn1 and the Lsm1-7 heptamer. To determine which of the two pathways is important for AMD in live cells, we targeted components of both pathways using short interfering RNA in human HT1080 cells. We show that Xrn1 and Lsm1 are essential for AMD. On the other side, out of three exosome components tested, only knockdown of PmScl-75 caused a strong inhibition of AMD. Our results show that mammalian cells, similar to yeast, require the 5'-3' Xrn1 pathway to degrade ARE-mRNAs.


Banded figers in high temperature coacervates of elastin peptides.
Electron micrographs of negatively stained coacervates of the synthetic polypentapeptide of propoelastin and of alpha-elastin exhibit banded fibers when the coacervates are formed, stained, and dried at temperatures greater than 50 degrees. This apparent increase in order occurs at the same temperature as an increase in order in aqueous solution and as a change in the volume expansion coefficient of fibrous elastin.


Vestibular and somatosensory interaction in the cat vestibular nuclei.
The vestibular nuclei of cats were explored extracellulary with micropipettes to locate units with a resting discharge rate which responded to rotation in the horizontal plane. These units were examined for somatosensory input from neck and limbs. Fewer than half responded to somatosensory stimulation. The neck region was the body area most effective in influencing unitary activity. The response pattern most often noted was an increase and decrease in discharge frequency when the body was moved towards and away from the recording electrode respectively. Change in discharge rate was observed to be primarily dependant upon neck velocity and not upon absolute neck position. Half of the somatosensory units received input from either the forelimbs or the hindlimbs, while the remaining half responded to both.


Assessment of the health status of 2,499 dermatological outpatients using the 12-item Medical Outcomes Study Short Form (SF-12) questionnaire.
In dermatological research and clinical practice it is important to evaluate the burden of the disease. To assess whether the 12-item Short Form of the Medical Outcomes Study (SF-12) could yield a valid description of the health status of a large number of dermatological outpatients. The SF-12 and the 12-item General Health Questionnaire (GHQ-12) were utilized. Questionnaires were self-completed by the outpatients in the waiting rooms. At the end of the visit the dermatologists recorded the diagnosis and the evaluation of the clinical severity. Data were complete for 2499 patients. We observed a reduction in the Physical Component Summary score (PCS-12) with increasing age, while the Mental Component Summary score (MCS-12) was stable. PCS-12 and MCS-12 scores were worse in women. Twenty-three per cent of patients were identified as GHQ-12 positive. GHQ-12-positive patients ('cases') had lower PCS-12 and MCS-12 scores compared with GHQ-12-negative patients (mean ± SD, PCS-12: 47·9 ± 10·8 vs. 52·2 ± 6·6; MCS-12: 35·2 ± 10·2 vs. 50·9 ± 78·3, respectively). High correlations between the MCS-12 score and the GHQ-12 were documented overall (-0·690, P < 0·001) and for single skin diseases. The impact of dermatological diseases is high for the mental components of health status; the mean scores for MCS-12 were low, and lower in patients identified as GHQ-12 'cases'. The picture of the general health status of patients with skin diseases given by the SF-12 allows meaningful comparisons both within dermatological conditions and with diseases in other specialties, as well as within categories of clinical severity and psychological well-being in single skin conditions.


Lower concentrations of receptor for advanced glycation end products and epiregulin in amniotic fluid correlate to chemically induced cleft palate in mice.
This study investigated the correlation between differentially expressed proteins in amniotic fluid (AF) and cleft palate induced by all-trans retinoic acid (atRA), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice. Seven proteins were differentially expressed at embryonic day (E) 16.5 in atRA and control groups as revealed by label-based mouse antibody array. Enzyme-linked immunosorbent assay was further used to detect the expression levels of these proteins in AF from E13.5 to E16.5 in atRA, TCDD, and control groups. The cleft palate groups showed lower concentrations of receptor for advanced glycation end products (RAGE) and epiregulin at E16.5. RAGE immunostaining obviously decreased in palatal tissue sections obtained from E14.5 to E16.5 in the cleft palate groups as revealed by immunohistochemistry. These findings indicate that reduced levels of RAGE and epiregulin in AF are correlated to chemically induced cleft palate in mice.


Comparison between weight gain and Fenton preterm growth z scores in assessing the risk of retinopathy of prematurity.
Several studies have shown that postnatal weight gain is a significant predictor for retinopathy of prematurity (ROP) in preterm infants. Using a cohort of 1,301 infants from a single-center ROP registry, we investigated whether incorporation of changes in Fenton preterm growth curve z scores (ie, deviation from the population average) provides improved predictive ability for developing ROP compared to weight gain alone. Three logistic regressions were fit to severe ROP: (1) baseline model that included gestational age and birth weight, (2) the baseline model adding weight gain, and (3) the baseline model adding change in z score. The area under the receiver operating characteristic curve (C index) was used to compare models. Both weight gain and change in z scores were significant predictors after adjusting for birth weight (P = 0.01) and gestational age (P < 0.01). The C indices were not significantly improved by including weight gain or z score to the baseline model; however, for a subset of subjects, change in weight z score may be a more useful measure compared to simple weight gain with regards to assessing risk for severe ROP.


MRI of recurrent rectosigmoid carcinoma.
A prospective study was performed to determine the most reliable MRI criteria to distinguish recurrent rectosigmoid carcinoma from benign postoperative fibrosis. Twenty-two consecutive patients who were suspected to have recurrent rectosigmoid carcinoma were examined by T2 and precontrast and contrast enhanced T1 weighted images. The prospective interpretations, the presence of high signal on T2 weighted images, the shape of the margins of a mass and the degree of contrast enhancement were correlated with histology and follow up to determine their respective accuracies, sensitivities and specificities. The best criteria for recurrent tumor was the combination of high signal on T2 weighted images, round margins and > 40% contrast enhancement, which had an accuracy of 92%, sensitivity of 100% and specificity of 85%. In patients who were more than one year postoperative the specificity was 100%. The most reliable MRI criteria for distinguishing recurrent rectosigmoid carcinoma from benign postoperative fibrosis are the combination of the signal intensity on T2 weighed images, the shape of the margins of a mass and the presence of greater than 40% contrast enhancement.


Tetraselmis as a challenge organism for validation of ballast water UV systems.
Transport and release of waterborne organisms as a result of ballasting and de-ballasting operations is widely acknowledged to represent an important mechanism for invasions by non-indigenous species. Regulatory requirements have been implemented globally to require treatment of ballast water before its release to the environment as a means of minimizing risks of invasion. UV-based processes represent an option for ballast water treatment; however, their use will require development of appropriate methods for reactor validation. To address this need, Tetraselmis was examined as challenge organism using a most probable number (MPN) assay for quantification of the concentration of viable (reproductively active) cells in suspension. A low pressure collimated-beam reactor was used to investigate UV254 dose-response behavior of Tetraselmis. Based on the experimental conditions applied, Tetraselmis indicated 4.5-5 log10 units of inactivation for UV254 doses of approximately 120 mJ/cm2, with no apparent change of resistance resulting from repeated exposure. A medium pressure UV collimated-beam reactor equipped with a series of narrow bandpass optical filters was used to investigate the action spectrum of Tetraselmis for wavelengths ranging from 228 nm-297 nm. Radiation with wavelengths in the range 254-280 nm was observed to be most efficient for inactivation of Tetraselmis. Additionally, DNA was extracted from Tetraselmis to allow measurement of its absorption spectrum. These results indicated strong absorbance from 254 nm to 280 nm, thereby suggesting that damage to DNA plays an important role in the inactivation of Tetraselmis sp. However, deviations of the action spectrum shape from the shape of the DNA absorption spectrum suggest that UV-induced damage to biomolecules other than DNA may contribute to Tetraselmis inactivation at some wavelengths in the UVC range.


Is that fear? Domestic dogs' use of social referencing signals from an unfamiliar person.
The aim of this study was to investigate whether dogs could successfully interpret a 'social referencing' cue (either happiness or fear) toward an object after viewing a human emotional expression. Fearful expressions are more likely to be unfamiliar to dogs, and thus they may not understand the meaning of such expressions. When confused, dogs could avoid contact with an object as in Merola et al. (2012, 2011). The present study compared an experimenter's fearful or happy response when an ambiguous object appeared with a control condition (experimenter was confusing). We examined 114 dogs in one of three conditions; happiness, fearful and the control. We found that dogs were more attentive to the experimenter when she displayed the fearful and control expressions compared to when happy, with no difference between the control and fear conditions. When left alone with the toy, they showed a similar pattern--more interest in the toy in both the fearful and control conditions. Our findings suggest that dogs may not understand the cues in the fearful and control conditions and instead respond with a possible attempt to gain more information from the experimenter.


Ergodicity of complex dynamics and quantum tunneling in nonintegrable systems.
The instanton approximation is a widely used approach to construct the semiclassical theory of tunneling. The instanton path bridges the regions that are not connected by classical dynamics, but the connection can be achieved only if the two regions have the same energy. This is a major obstacle when applying the instanton method to nonintegrable systems. Here we show that the ergodicity of complex orbits in the Julia set ensures the connection between arbitrary regions and thus provides an alternative to the instanton path in the nonintegrable system. This fact is verified using the ultra-near integrable system in which none of the visible structures inherent in nonintegrability exist in the classical phase space, yet nonmonotonic tunneling tails emerge in the corresponding wave functions. The simplicity of the complex phase space allows us to explore the origin of the nontrivial tunneling tails in terms of semiclassical analysis in the time domain. In particular, it is shown that not only the imaginary part but also the real part of the classical action plays a role in creating the characteristic step structure of the tunneling tail that appears as a result of the quantum resonance.


IGFBP-3: a cell fate pivot in cancer and disease.
One of the hallmarks in the advancement of cancer cells is an ability to overcome and acquire resistance to adverse conditions. There has been a large amount of cancer research on IGFBP-3 as a pro-apoptotic molecule in vitro. These pro-apoptotic properties, however, do not correlate with several studies linking high IGFBP-3 levels in breast cancer tissue to rapid growth and poor prognosis. Evidence is emerging that IGFBP-3 also exhibits pro-survival and growth-promoting properties in vitro. How IGFBP-3 pivots cell fate to either death or survival, it seems, comes down to a complex interplay between cells' microenvironments and the presence of cellular IGFBP-3 binding partners and growth factor receptors. The cytoprotective actions of IGFBP-3 are not restricted to cancer but are also observed in other disease states, such as retinopathy and brain ischaemia. Here we review the literature on this paradoxical nature of IGFBP-3, its pro-apoptotic and growth-inhibitory actions versus its cytoprotective and growth-potentiating properties, and discuss the implications of targeting IGFBP-3 for treatment of disease.


Soliton excitation in waveguide arrays with an effective intermediate dimensionality.
We reveal and observe experimentally significant modifications undertaken by discrete solitons in waveguide lattices upon the continuous transformation of the lattice structure from one-dimensional to two-dimensional. Light evolution and soliton excitation in arrays with a gradually increasing number of rows are investigated, yielding solitons with an effective reduced dimensionality residing at the edge and in the bulk of the lattice.


Synthesis of a biodegradable tadpole-shaped polymer via the coupling reaction of polylactide onto mono(6-(2-aminoethyl)amino-6-deoxy)-beta-cyclodextrin and its properties as the new carrier of protein delivery system.
A new tadpole-shaped polymer was synthesized via the coupling reaction of poly(DL-lactide) (PLA) onto mono(6-(2-aminoethyl)amino-6-deoxy)-beta-cyclodextrin (CDen) using N,N'-Dicyclohexycarbodiimide as the catalyst. The structures of CDenPLA as the products were characterized with infrared spectrometry, nuclear magnetic resonance and their molecular weights were determined by gel permeation chromatography. The tadpole-shaped polymer possessed both a hydrophilic head that could bind some residues on a protein and a hydrophobic polylactide tail so that it could be amphiphilic. Two methods, double emulsion (DE) and nanoprecipitation (NP), were employed to fabricate the polymeric nanoparticles into which the bovine serum albumin was loaded as a model protein. The nanoparticles with a hydrophobic core of the PLA segments covered with the hydrophilic corona layer of the cyclodextrin moiety could be formed from the copolymers using NP method as identified by 1HNMR. Influence of the preparation conditions on the nanoparticles size, encapsulation efficiency and release profile in vitro was investigated. The encapsulation efficiency of the BSA-loaded nanoparticles with the average diameter of 377 nm was 71.6% under an optimized condition. The structure maintenance in the nanoparticle preparation and release in vitro was also measured via sodium dodecyl sulfate polyacrylamide gel electrophoresis and circular dichroism spectrometry. The results showed that the new copolymer could load BSA effectively and BSA kept stable after it was released from the nanoparticles.


[Isotope study of the effects of a nitrate derivative on pulmonary blood volume. Application in the treatment of cardiogenic pulmonary edema].
Isotopic study of pulmonary and ventricular blood volumes after the ingestion of 5 mg of isosorbide dinitrate showed that cardio-pulmonary blood volume decreased by 380 ml without any change in total circulating blood volume. The demonstration of this effective "internal venesection" explains the fall in capillary pressure seen after the administration of nitrate derivatives. It justifies their use in the treatment of acute pulmonary oedema or refractory cardiac failure and explains the results observed.


Commercial afforestation can deliver effective climate change mitigation under multiple decarbonisation pathways.
Afforestation is an important greenhouse gas (GHG) mitigation strategy but the efficacy of commercial forestry is disputed. Here, we calculate the potential GHG mitigation of a UK national planting strategy of 30,000 ha yr-1 from 2020 to 2050, using dynamic life cycle assessment. What-if scenarios vary: conifer-broadleaf composition, harvesting, product breakouts, and decarbonisation of substituted energy and materials, to estimate 100-year GHG mitigation. Here we find forest growth rate is the most important determinant of cumulative mitigation by 2120, irrespective of whether trees are harvested. A national planting strategy of commercial forest could mitigate 1.64 Pg CO2e by 2120 (cumulative), compared with 0.54-1.72 Pg CO2e for planting only conservation forests, depending on species composition. Even after heavy discounting of future product substitution credits based on industrial decarbonisation projections, GHG mitigation from harvested stands typically surpasses unharvested stands. Commercial afforestation can deliver effective GHG mitigation that is robust to future decarbonisation pathways and wood uses.


Immunohistochemistry with a mutation-specific monoclonal antibody as a screening tool for the BRAFV600E mutational status in primary cutaneous malignant melanoma.
The V600E mutation of BRAF has emerged as both an effective biomarker and therapeutic target for select benign and malignant cutaneous and non-cutaneous human tumors and is typically determined using DNA-based techniques that include allele-specific PCR and direct DNA sequencing. Recently however, the development of new antibodies directed against the V600E protein has opened the door for an easier and more efficient strategy for identifying this mutation. Our present aim was to determine the efficacy of one such antibody, anti-B-Raf (V600E), a mouse monoclonal antibody in which the immunogen is a synthetic peptide derived from the internal region of BRAFV600E. A total of 35 cases of primary cutaneous melanoma were evaluated using a combination of DNA-based techniques that included allele-specific PCR and/or direct DNA sequencing and immunohistochemistry. Cases of papillary thyroid carcinomas (n=5) and colorectal carcinomas (n=5), known to harbor the BRAFV600E mutation, served as positive controls for the study. DNA analyses revealed that 6 of 35 (17%) cases of the primary cutaneous malignant melanoma possessed the BRAFV600E mutation. For immunohistochemical analyses, cytoplasmic positivity with anti-B-Raf was noted in 7 of 35 (20%) cases of primary melanoma and in all 10 positive controls. Statistical analyses of the data demonstrated that the sensitivity of the immunohistochemistry was 100% and specificity was 97%. Findings from the current study support the potential use of immunohistochemistry as an ancillary screening tool to assess the BRAFV600E mutation status in primary cutaneous melanoma.


A protein oxidase catalysing disulfide bond formation is localized to the chloroplast thylakoids.
In chloroplasts, thiol/disulfide-redox-regulated proteins have been linked to numerous metabolic pathways. However, the biochemical system for disulfide bond formation in chloroplasts remains undetermined. In the present study, we characterized an oxidoreductase, AtVKOR-DsbA, encoded by the gene At4g35760 as a potential disulfide bond oxidant in Arabidopsis. The gene product contains two distinct domains: an integral membrane domain homologous to the catalytic subunit of mammalian vitamin K epoxide reductase (VKOR) and a soluble DsbA-like domain. Transient expression of green fluorescent protein fusion in Arabidopsis protoplasts indicated that AtVKOR-DsbA is located in the chloroplast. The first 45 amino acids from the N-terminus were found to act as a transit peptide targeting the protein to the chloroplast. An immunoblot assay of chloroplast fractions revealed that AtVKOR-DsbA was localized in the thylakoid. A motility complementation assay showed that the full-length of AtVKOR-DsbA, if lacking its transit peptide, could catalyze the formation of disulfide bonds. Among the 10 cysteine residues present in the mature protein, eight cysteines (four in the AtVKOR domain and four in the AtDsbA domain) were found to be essential for promoting disulfide bond formation. The topological arrangement of AtVKOR-DsbA was assayed using alkaline phosphatase sandwich fusions. From these results, we developed a possible topology model of AtVKOR-DsbA in chloroplasts. We propose that the integral membrane domain of AtVKOR-DsbA contains four transmembrane helices, and that both termini and the cysteines involved in catalyzing the formation of disulfide bonds face the oxidative thylakoid lumen. These studies may help to resolve some of the issues surrounding the structure and function of AtVKOR-DsbA in Arabidopsis chloroplasts.


Descending thoracic and thoracoabdominal aortic aneurysm in patients with Takayasu's disease.
From June 1974 to December 2001 we performed operative treatment on 33 patients with descending thoracic or thoracoabdominal aortic aneurysm in association with Takayasu disease. There were 25 men and 8 women with a mean age of 40.2A years (range 16-64A years). Nineteen patients came from North Africa, 6 were from France, and 8 were from various locations in the world. The revealing symptom was hypertension in 12 cases, thoracic or abdominal pain in 7, isolated inflammatory syndrome in 5, neurologic or ocular manifestations in 3, rupture in 3, and embolization to the lower extremity in 1. In the remaining two cases discovery was coincidental. The aneurysm was confined to the thoracic aorta in 10 cases and involved both the thoracic and abdominal aorta in 23 cases. There were 8 type I, 6 type II, 4 type III, and 5 type IV aneurysms according to Crawford's classification. Two patients had undergone previous repair of the thoracoabdominal aorta. Four patients required first-stage treatment of a renal artery lesion to control hypertension. Six patients had associated aneurysms of the proximal aorta, including five treated via the distal elephant trunk technique in first-stage procedures. Aneurysm repair consisted of prosthetic replacement of the thoracoabdominal aorta in 31 cases, exclusion bypass in 1 case, and stent graft placement in 1 case. The procedure was performed with cross-clamping alone in 13 cases, distal perfusion in 17 cases, and deep hypothermic circulatory arrest in 3 cases. Twenty patients (61%) had associated renal and/or intestinal artery lesions that were treated during the same procedure as that for the thoracoabdominal aorta in 19 patients (58%). A total of 24 procedures were performed on renal arteries (17 revascularizations, 7 nephrectomies). Associated supraaortic trunks lesions were present in 15 patients (45%) and were treated in 12 patients, including 8 in first-stage procedures prior to thoracoabdominal aortic aneurysm repair. Three patients died of multiple organ failure, after reoperation in two cases and infection in one case involving prior long-term corticosteroid therapy. Three patients developed paraplegia, including one who had undergone emergency treatment following rupture. Two patients required reoperation, for hematoma in one case and bowel necrosis in one. Four patients developed respiratory complications requiring artificial ventilation for more than 48 hr. During follow-up, two patients died from complications after repair of the proximal aorta and one patient required nephrectomy. Despite the extent of aneurysmal lesions and high frequency of association with visceral and supraaortic vessel lesions, the outcome of surgery in patients presenting with descending thoracic or thoracoabdominal aortic aneurysm in association with Takayasu disease was satisfactory.


Scent mark signal investment predicts fight dynamics in house mice.
Signals mediate competitive interactions by allowing rival assessment, yet are often energetically expensive to produce. One of the key mechanisms maintaining signal reliability is social costs. While the social costs of over-signalling are well known, the social costs of under-signalling are underexplored, particularly for dynamic signals. In this study, we investigate a dynamic and olfactory-mediated signalling system that is ubiquitous among mammals: scent marking. Male house mice territorially scent mark their environment with metabolically costly urine marks. Competitive male mice are thought to deposit abundant scent marks in the environment. However, we recently identified a cohort of low-marking males that win fights. We hypothesized that there may be social costs imposed on individuals who under-invest in signalling. Here we find that scent mark investment predicts fight dynamics. Winning males that produce fewer scent marks prior to a fight engage in more intense fights that take longer to resolve. This effect appears to be driven by an unwillingness among losers to acquiesce to weakly signalling winners. We, therefore, find evidence for rival assessment of scent marks as well as social costs to under-signalling. This supports existing hypotheses for the importance of social punishment in maintaining optimal signalling equilibria. Our results further highlight the possibility of diverse signalling strategies in house mice.


Prevalence and clinical correlates of co-occurring insomnia and hypersomnia symptoms in depression.
The aim was to examine the prevalence and consequences of co-occurring insomnia and hypersomnia symptoms in depressed adults drawn from a representative sample of the U.S. population. Data from 687 National Comorbidity Survey Replication (NCS-R) respondents meeting criteria for a major depressive episode (MDE) in the past year were included. Respondents completed clinical interviews that assessed 12-month DSM-IV disorders, impairment, mental health treatment, and depressive symptom severity. Outcomes were compared between respondents who experienced insomnia symptoms-only (N=404), hypersomnia symptoms-only (N=44), both insomnia and hypersomnia symptoms (N=184) and no sleep problems (N=55) during an MDE. Insomnia and hypersomnia symptoms co-occurred in 27.7% of respondents with past-year MDEs, most frequently in bipolar spectrum disorders and major depressive disorder with dysthymia. Similar to the insomnia-only group, respondents with co-occurring sleep disturbances had more severe depression, and higher rates of past-year impulse control disorders and suicide planning. Similar to the hypersomnia-only group, respondents with co-occurring sleep disturbances had higher rates of past-year drug use disorders and suicide attempts. Compared to the insomnia-only and no sleep problem groups, respondents with both sleep disturbances were more frequently in mental health treatment, seeing a general practitioner, and taking antidepressants. The NCS-R is cross-sectional and did not evaluate sleep disorder diagnoses. Co-occurring insomnia and hypersomnia symptoms were associated with a more severe MDE. Further research is warranted to more fully understand the joint presentation of insomnia and hypersomnia in depression.


Sulphur fertilization enhanced yield, its uptake, use efficiency and economic returns of Aloe vera L.
Sulphur plays a vital role in the formation and biosynthesis of protein, chlorophyll, and few amino acids. To investigate the effect of sulphur fertilizer on leaf biomass yield, critical sulphur concentration, sulphur requirement and uptake by Aloe vera L., a pot experiment was carried out following completely randomized design with six levels of sulphur viz., 0, 15, 30, 45, 60 and 80 kg ha-1 with three replications. The results of the study revealed that the growth attributes, leaf and gel yield, and sulphur uptake significantly improved with sulphur application and the best results were obtained from the application of 45 kg sulphur ha-1. On average, addition of sulphur enhanced the leaf biomass yield by 47.5% and sulphur use efficiency by 38% compared to control. The effect of sulphur on the growth parameters and their significant and positive correlations with yield signifies the importance of sulphur on the yield and quality of A. vera. The calculated minimum amount of sulphur for 80% leaf biomass production was 21.1 kg sulphur ha-1 with a critical leaf sulphur concentration of 0.23% in A. vera. Moreover, sulphur addition to soil substantially enhanced the economic returns of A. vera. Therefore, addition of 45 kg sulphur ha-1 could be a better option for obtaining higher yield and economic return of A. vera.


Monomaleimidogold labeling of the gamma subunit of the Escherichia coli F1 ATPase examined by cryoelectron microscopy.
A novel approach for locating sites of interest in a protein complex has been developed using monomaleimidonanogold (MMN). The Escherichia coli F1 ATPase, when prepared without the delta subunit, contains only a single reactive cysteine on one of the three copies of the alpha subunit. This site was reacted with MMN and the gold cluster visualized on the protein complex by cryoelectron microscopy. Additional sites for modification with MMN were added by introducing cysteine residues through site-directed mutagenesis. Labeling of two mutants, gamma S8-C and gamma T106-C, in which Ser8 and Thr106, respectively, had been replaced by a cysteine, placed the gold cluster on the central mass that is seen in the hexagonal projection of the ECF1 complex. The results establish that the central mass contains the N-terminal part of the gamma subunit.


Hepatitis C virus infection in young, low-income women: the role of sexually transmitted infection as a potential cofactor for HCV infection.
We evaluated risk for hepatitis C virus (HCV) infection in women residing in low-income neighborhoods of northern California. A population-based sample of 1707 women, aged 18 to 29, were surveyed and screened for sexually transmitted infections and HCV. Women infected with HCV (2.5%) were more likely to have a history of injection and noninjection drug use, to exchange sex for money or drugs, and to have sexually transmitted infections. HCV was independently associated with history of injection drug use, herpes simplex virus type 2 (HSV-2) infection, and heroin and cocaine use. Injection drug use is the highest risk exposure for HCV, but HSV-2 and noninjection drug use contribute significantly to increased risk. HCV prevention programs in impoverished areas should integrate drug treatment and sexually transmitted infection control.


Posterior ischaemic optic neuropathy: clinical features, pathogenesis, and management.
To investigate and present a comprehensive account of the clinical features, pathogenesis, and management of posterior ischaemic optic neuropathy (PION). This retrospective study is based on 53 consecutive eyes of 42 patients with PION seen in my clinic since 1973, who fulfilled the inclusion criteria. They were systematically evaluated, treated, and followed by me. All patients had initially detailed ophthalmic evaluation of the anterior and posterior segments, including visual field with Goldmann perimeter and fluorescein fundus angiography. All patients aged 50 years and older were also investigated for giant cell arteritis (GCA). Every attempt was made to rule out other causes of visual loss. Follow-up evaluation was similar to the initial evaluation except angiography. Aetiologically, PION can be divided into three types: arteritic due to GCA, nonarteritic not due to GCA, and surgical following a surgical procedure. Steroid therapy was given to only those nonarteritic PION patients who opted to try that, but was given to all arteritic PION patients. PION was nonarteritic in 28 patients (35 eyes), arteritic in 12 (14 eyes), and surgical in three (four eyes). Visual acuity varied between 20/20 and no light perception--it was count fingers or less in 19 of 35 eyes with nonarteritic PION, four of 14 in arteritic, and all four with surgical PION. The most common visual field defect was central visual loss, alone or in combination with other types of visual field defects. Initially, optic disc and fundus showed no abnormality but the disc usually developed pallor in about 6-8 weeks. Aggressive treatment with high-dose systemic steroid during the very early stages of nonarteritic PION produced significant improvement of visual acuity as well as visual fields, but not so in arteritic or surgical PION. However, some spontaneous visual improvement also occurred in some untreated nonarteritic PION cases. PION is a distinct clinical entity but should be diagnosed only after exclusion of all other causes of visual loss. In all patients older than 50, GCA must be ruled out. There is usually marked visual loss, with central field defect being the most common. The study suggests that high-dose steroid therapy in nonarteritic PION, soon after the onset of visual loss, resulted in significant visual improvement compared to the untreated cases, but not in arteritic and surgical PION.


Developing a system of student nurse profiling through action research.
This article concerns the early stages of a research study which attempted to improve the assessment of student nurses' clinical competence by means of profiling. During the course of the paper the reasons for undertaking assessment will be considered, the existing assessment approach will be briefly reviewed, the use of action research as the method of inquiry will be addressed, and the initial findings from the study described.


An antibody binding-based fluorescent assay for the rapid quantification of globotriaosylceramide levels in human Fabry cells.
Fabry disease is caused by reduced α-GAL A activity and accumulation of globotriaosylceramide (Gb3). Here, we describe a microplate Gb3 assay using fluorophore-tagged antibody and crude cellular lipid extracts. The assay is able to detect higher Gb3 concentrations in human Fabry cells compared to non-diseased cells. This result was verified by immunofluorescence staining that revealed large amounts of Gb3 deposits in Fabry cell lines, demonstrating the accuracy of this method. This assay may provide the basis for detecting Fabry disease by quantifying Gb3 deposits from human biological samples, for example, from urine and blood.


Relevance of 18F-DOPA visual and semi-quantitative PET metrics for the diagnostic of Parkinson disease in clinical practice: a machine learning-based inference study.
To decipher the relevance of visual and semi-quantitative 6-fluoro-(18F)-L-DOPA (18F-DOPA) interpretation methods for the diagnostic of idiopathic Parkinson disease (IPD) in hybrid positron emission tomography (PET) and magnetic resonance imaging. A total of 110 consecutive patients (48 IPD and 62 controls) with 11 months of median clinical follow-up (reference standard) were included. A composite visual assessment from five independent nuclear imaging readers, together with striatal standard uptake value (SUV) to occipital SUV ratio, striatal gradients and putamen asymmetry-based semi-quantitative PET metrics automatically extracted used to train machine learning models to classify IPD versus controls. Using a ratio of 70/30 for training and testing sets, respectively, five classification models-k-NN, LogRegression, support vector machine, random forest and gradient boosting-were trained by using 100 times repeated nested cross-validation procedures. From the best model on average, the contribution of PET parameters was deciphered using the Shapley additive explanations method (SHAP). Cross-validated receiver operating characteristic curves (cv-ROC) of the most contributive PET parameters were finally estimated and compared. The best machine learning model (k-NN) provided final cv-ROC of 0.81. According to SHAP analyses, visual PET metric was the most important contributor to the model overall performance, followed by the minimum between left and right striatal to occipital SUV ratio. The 10-time cv-ROC curves of visual, min SUVr or both showed quite similar performance (mean area under the ROC of 0.81, 0.81 and 0.79, respectively, for visual, min SUVr or both). Visual expert analysis remains the most relevant parameter to predict IPD diagnosis at 11 months of median clinical follow-up in 18F-FDOPA. The min SUV ratio appears interesting in the perspective of simple semi-automated diagnostic workflows.


Successful treatment of SAPHO syndrome with severe spinal disorder using entercept: a case study.
SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis) is a rare disease. Presently, there is no treatment guideline for this illness. Several studies suggested entercept, a novel biological agent against tumor necrosis factor-alpha, is effective in treating SAPHO syndrome. We report a case in which the clinical conditions of a middle-aged female patient diagnosed with SAPHO syndrome, with noted spinal disorder, improved significantly after receiving entercept treatment. The patient remained stable after 3-month follow-up.


Accuracy of endoscopic ultrasound in staging and restaging patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation.
To date, the role of endoscopic ultrasound (EUS) in restaging locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (NAT) have not been thoroughly investigated. To evaluate accuracy and clinical usefulness of EUS for both staging and restaging LARC. According to EUS staging, patients with LARC were enrolled in the study. Those who underwent surgery directly represented a control group useful for evaluating the accuracy of EUS in staging LARC. In the study group, EUS was repeated seven weeks after NAT, before surgery. The results of EUS were compared with the corresponding pTN stages. From 2000 to 2006, 212 consecutive patients with RC underwent EUS staging. Among them EUS diagnosed 162 LARC (M/F = 93/69; mean age: 60 years [range 40-80]). The final study group included 85 patients with LARC. EUS restaging had an overall accuracy of 61% and 59% for T and N-stage, respectively. In the control group, the accuracy of EUS in staging LARC was 86% and 58% for T and N-stage, respectively. EUS accurately stages LARC and enables appropriate decision-making, with selection of those patients who need NAT. On the other hand, EUS restaging of LARC after NAT has low accuracy and should not be used in clinical practice.


J chain in malignant human IgG immunocytes.
J chain was demonstrated directly by immunofluorescence in the cytoplasm of malignant IgG-producing human tumor cells. This was in contrast to IgG immunocytes accumulating in foci of chronic inflammation, which generally were devoid of J chain.


Whole genome mapping and identification of single nucleotide polymorphisms of four Bangladeshi individuals and their functional significance.
The major objective of the study was to sequence the whole genome of four Bangladeshi individuals and identify variants that are known to be associated with functional changes or disease states. We also carried out an ontology analysis to identify the functions and pathways most likely to be affected by these variants. We identified around 900,000 common variants and close to 5 million unique ones in all four of the individuals. This included over 11,500 variants that caused nonsynonymous changes in proteins. Heart function associated pathways were heavily implicated by the ontology analysis; corroborating previous studies that claimed the Bangladeshi population as highly susceptible to heart disorders. Two variants were found that have been previously identified as pathogenic factors in familial hypercholesteremia and structural disorders of the heart. Other pathogenic variants we found were associated with pseudoxanthoma elasticum, cancer progression, polyagglutinable erythrocyte syndrome, preeclampsia, and others.


Epitope Analysis of Anti-SARS-CoV-2 Neutralizing Antibodies.
Coronavirus disease 2019 is threatening thousands of millions of people around the world. In the absence of specific and highly effective medicines, the treatment of infected persons is still very challenging. As therapeutics, neutralizing antibodies (NAbs) have great potential. Many NAbs have been reported, and most target various regions on the receptor-binding domain of the spike (S) protein, or the N-terminal domain. Several NAbs and NAb cocktails have been authorized for emergency use, and more are in clinical trials or are under development. In this review, considering the angle of binding epitopes on the S protein, we summarize the functions and the underlying mechanisms of a set of well-recognized NAbs and provide guidance for vaccine design and the combinatorial use of these antibodies. In addition, we review the NAbs and NAb cocktails that have been approved for emergency use and discuss the effectiveness of these NAbs for combating severe acute respiratory syndrome coronavirus 2 mutants.


Concanavalin A surface receptors and cytoplasmic actin in cell adhesion.
A double immunofluorescence staining technique to locate concanavalin A (Con A) surface receptors and cytoplasmic actin in the same cell was applied to monolayer cultures of rat foetal fibroblasts during cell detachment induced by trypsin and during cell attachment to glass substratum. Con A receptors were demonstrated by fluorescein-isothiocyanate-labelled Con A (FITC-Con A) and actin by specific anti-actin antibody (AAA) traced with rhodamine-labelled goat anti-human globulin (R-AHG). Untreated, control cells had an elongated shape, Con A receptors restricted to cell margins and prominent actin filaments. After 2 min treatment with 0.001% trypsin the cells became angular with Con A receptors in clusters and actin in a diffuse or aggreagate staining pattern. Progressive cell rounding followed and this was accompanied by the development of long, thin, arborized cell processes, studded with Con A receptors and containing fine actin filaments. Complete cell rounding preceded cell detachment. The sites of detached cells were marked by fine aggregates containing Con A receptors and actin. In cells attaching to a glass substratum, actin was present in a diffusely stained or aggregate pattern in round cells, in filaments restricted to cell margins in partially spread cells and in numerous filaments in fully spread cells. Con A receptors were present in clusters in round cells, in clusters or caps in partially spread cells and in cell margins in fully spread cells. Binding of FITC-Con A to partially spread cells resulted in dissolution of the few, newly formed, actin filaments. We believe our observations are consistent with the idea that actin filaments, formed during cell attachment, contribute towards the maintenance of cell adhesion by helping in the preservation of cell shape and by anchorage of Con A receptors at points of cell attachment to the substratum.