Water quality assessment of the ecologically stressed Hooghly River Estuary, India: A multivariate approach.
Spatio-temporal and seasonal variation of the water quality characteristics of the Hooghly River Estuary, India were studied considering eight stations of diverse eco-hydrological characteristics. Wide variations in turbidity, total dissolved solids and fecal coliform exceeded the permissible BIS drinking water level limit. The estuary is observed to be relatively low-oxygenated, mesotropic and phosphate limiting. Spatial heterogeneity and impact of the southwest monsoon were remarkably pronounced in the distribution of the inorganic nutrients revealing the following values (expressed in μgatml-1): nitrate+nitrite (2.42-37.19), phosphate (0.41-1.52) and silicate (38.5-187.75). Water Quality Index (WQI) values confirmed the prevailing 'bad' condition, detrimental for sustenance of aquatic biota. Results of Principal Component Analysis identified the major factors liable for water quality deterioration while cluster analysis categorized the stations on the basis of similar water quality status. The authors recommend adopting preventive measures for water quality improvement linked to biodiversity conservation.


99mTechnetium-labelled red blood cell scintigraphy as an alternative to angiography in the investigation of gastrointestinal bleeding: clinical experience in a district general hospital.
99mTechnetium-labelled red blood cell scintigraphy (99mTc RBC scintigraphy) was used as the second-line investigation to localise bleeding in 23 patients (11 male, 12 female; mean age 67 years) presenting with active bleeding per rectum. Scintigraphy was available on a 24 h basis. A total of 18 patients had positive scans (78%). Surgery was performed urgently in 11 patients and the site of bleeding, as predicted by scintigraphy, was confirmed in 9 (82%). 99mTc RBC scintigraphy was less useful in patients who were not bleeding actively or who were being investigated for chronic anaemia. This study suggests that 99mTc RBC scintigraphy can play a useful role in the preoperative localisation of unexplained gastrointestinal bleeding in hospitals with nuclear medicine facilities, but confirms it has little place in the management of patients unless they are bleeding actively.


Macromolecule mass spectrometry: citation mining of user documents.
Identifying research users, applications, and impact is important for research performers, managers, evaluators, and sponsors. Identification of the user audience and the research impact is complex and time consuming due to the many indirect pathways through which fundamental research can impact applications. This paper identified the literature pathways through which two highly-cited papers of 2002 Chemistry Nobel Laureates Fenn and Tanaka impacted research, technology development, and applications. Citation Mining, an integration of citation bibliometrics and text mining, was applied to the >1600 first generation Science Citation Index (SCI) citing papers to Fenn's 1989 Science paper on Electrospray Ionization for Mass Spectrometry, and to the >400 first generation SCI citing papers to Tanaka's 1988 Rapid Communications in Mass Spectrometry paper on Laser Ionization Time-of-Flight Mass Spectrometry. Bibliometrics was performed on the citing papers to profile the user characteristics. Text mining was performed on the citing papers to identify the technical areas impacted by the research, and the relationships among these technical areas.


Establishing an efficient gene-targeting system in an itaconic-acid producing Aspergillus terreus strain.
To develop an efficient gene-targeting platform in an excellent itaconic acid producing strain Aspergillus terreus CICC40205. The frequency of homologous recombination was improved by deleting the ku80 gene. A nutritional transformation system based on the bidirectionally selectable marker, pyrG An , was established in the ku80-/pyrG-double mutant which is convenient for following marker rescue. The modified Cre/loxP recombination system was applied for the excision of the pyrG An marker by directly introducing Cre recombinase into the protoplasts. This gene-targeting system is an efficient platform for sequential and multiple genetic modifications in A. terreus and is conducive to study biosynthesis mechanisms and to improve the production ability of itaconic acid and other products.


The Promise and Future of Radiomics for Personalized Radiotherapy Dosing and Adaptation.
Quantitative image analysis, also known as radiomics, aims to analyze large-scale quantitative features extracted from acquired medical images using hand-crafted or machine-engineered feature extraction approaches. Radiomics has great potential for a variety of clinical applications in radiation oncology, an image-rich treatment modality that utilizes computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) for treatment planning, dose calculation, and image guidance. A promising application of radiomics is in predicting treatment outcomes after radiotherapy such as local control and treatment-related toxicity using features extracted from pretreatment and on-treatment images. Based on these individualized predictions of treatment outcomes, radiotherapy dose can be sculpted to meet the specific needs and preferences of each patient. Radiomics can aid in tumor characterization for personalized targeting, especially for identifying high-risk regions within a tumor that cannot be easily discerned based on size or intensity alone. Radiomics-based treatment response prediction can aid in developing personalized fractionation and dose adjustments. In order to make radiomics models more applicable across different institutions with varying scanners and patient populations, further efforts are needed to harmonize and standardize the acquisition protocols by minimizing uncertainties within the imaging data.


A duplex oligodeoxynucleotide-dendrimer bioconjugate as a novel delivery vehicle for doxorubicin in in vivo cancer therapy.
We designed a bioconjugate between duplex oligodeoxynucleotides (dODNs) and a dendrimer (DEN) and demonstrate its feasibility as a novel delivery system for doxorubicin (Dox) in animal tumor models and against cancer cells in vitro. The dODNs-DEN conjugates formed stable complexes with Dox (~184 Dox molecules per conjugate) and the resulting Dox-loaded conjugate exhibited a sustained drug release pattern both in vitro and in vivo. Pharmacokinetic studies showed that Dox-loaded dODNs-DEN conjugates were cleared from plasma much more slowly (up to 5.3h) than was free Dox (0.65h). Furthermore, tumors retained a higher amount of Dox in mice treated with the conjugate group compared to that of free Dox-treated group at the same dosage. In mice bearing 4T1 murine breast tumor allografts, the dendrimer conjugate, at a Dox concentration of 1mg/kg, was more effective than the equivalent concentration of free Dox and tumor size reduction was equivalent to that seen using 4mg/kg free Dox. We observed no severe systemic toxicity or cardiotoxicity in mice treated with the conjugate, as indicated by body weight change and heart tissue histology. These findings indicate that dODNs-DEN conjugates can be used to administer Dox with improved pharmacokinetics, lower toxicity, and an increased ability to concentrate drugs in tumors, compared with free drug, and that such conjugates are effective against tumors in vivo.


Rigorous control conditions diminish treatment effects in weight loss-randomized controlled trials.
It has not been established whether control conditions with large weight losses (WLs) diminish expected treatment effects in WL or prevention of weight gain (PWG)-randomized controlled trials (RCTs). We performed a meta-analysis of 239 WL/PWG RCTs that include a control group and at least one treatment group. A maximum likelihood meta-analysis framework was used to model and understand the relationship between treatment effects and control group outcomes. Under the informed model, an increase in control group WL of 1 kg corresponds with an expected shrinkage of the treatment effect by 0.309 kg (95% confidence interval (-0.480, -0.138), P=0.00081); this result is robust against violations of the model assumptions. We find that control conditions with large WLs diminish expected treatment effects. Our investigation may be helpful to clinicians as they design future WL/PWG studies.


Trophoblast apoptosis through polarization of macrophages induced by Chinese Toxoplasma gondii isolates with different virulence in pregnant mice.
Toxoplasma gondii is an apicomplexan parasite capable of transplacental transmission to cause spontaneous abortion or significant disease in the surviving neonate. Different from the dominant genotypes of T. gondii strains in European and North American which belong to three distinct clonal lineages, type I, type II, and type III, isolates from China possess the predominant genotype of China 1(ToxoDB#9) with a different virulence. The genotype-associated pathogenesis has been investigated previously. Based on two isolates of T. gondii from Chinese wild cats, a murine model of pregnancy and one transwell system in vitro, here we reported differentially polarized activation of macrophages induced by genotype China 1 strains, TgCtwh3 and TgCtwh6 with different virulence to mice, and its impact on trophoblast apoptosis. The results showed that macrophages were alternatively activated when infected with virulent TgCtwh3 while classically activated when infected with low virulent (cyst-forming) TgCtwh6 both in vitro and in vivo. By the analysis of flow cytometry, the percentage of the Th1 cells in two infection groups decreased significantly, and the Th2 cells from spleen escalated only in the virulent TgCtwh3 group. Interestingly, the high parasite burden was noted in the placenta of TgCtwh3-infected group whereas the inflammatory cells infiltration predominates in the TgCtwh6-infected group. In vivo trophoblast apoptosis in TgCtwh3 group was found to be more obvious when compared with TgCtwh6 although it was present in both. The present observations indicate that polarization of macrophages and modulation of Th subsets induced by the isolates with identical genotype but different virulence could contribute to trophoblast apoptosis through different mechanisms, suggesting a virulence-associated pathogenesis of T. gondii in abnormal pregnant outcome.


Gymnocranius obesus, a new large-eye seabream from the Coral Triangle.
Two previously recorded new species of the large-eye seabream genus Gymnocranius (Gymnocranius sp. D and Gymnocranius sp. E) remain undescribed. Here we describe Gymnocranius sp. E as Gymnocranius obesus sp. nov. This new species is morphologically distinct from all other known species under Gymnocranius by the following combination of characters: relatively deep body, with ratio of standard length to body depth 2.2-2.4; protruding large eye, with eye diameter about equal to or slightly larger than inter-orbital width; caudal fin moderately forked; no blue spots or wavy blue lines on cheek and snout in adults; fourth transversal dark bar on flank running from the sixth spine of the dorsal fin to the origin of the anal fin; anal, caudal and dorsal fins drab with yellowish to yellow margins. Gymnocranius obesus sp. nov. is distinct from G. griseus, with which it has been previously confused by a relatively larger head, scales above lateral line without dark basal patch, and a smaller number of front scales on the dorsal side of the head. Gymnocranius obesus sp. nov. is genetically distinct from its closest known relative, Gymnocranius sp. D by 104 diagnostic nucleotide characters, which translates into a 9.6% sequence divergence at the mitochondrial cytochrome b gene. Gymnocranius obesus sp. nov. reaches a length of at least 295mm. Its distribution, from the Ryukyu Islands to Bali, including Taiwan and the Flores Sea, mostly coincides with the western half of the Coral Triangle.


Cardiovascular risk in parents of children with extreme lipoprotein cholesterol levels: the Bogalusa Heart Study.
Fasting serum lipids, lipoprotein cholesterol, and other cardiovascular disease risk factors were examined in 321 natural parents of children with low and/or high levels of beta- and pre-beta-lipoprotein cholesterol. Parents of children from low pre-beta-lipoprotein groups had elevated alpha- and lower pre-beta-lipoprotein cholesterol levels. Parents whose children had high beta-lipoprotein cholesterol levels also had high serum total and beta-lipoprotein cholesterol levels. Parents of children with high levels of both beta- and pre-beta-lipoprotein cholesterol had a high prevalence of both abnormal risk factor levels, as well as clinical evidence of early coronary artery disease (before age 50 years). These observations show that parents of children with high beta- and/or pre-beta-lipoprotein cholesterol levels have greatly enhanced risk for cardiovascular disease, and children mirror their parents' lipoprotein cholesterol levels. These observations emphasize the need for cardiovascular risk evaluation early in life, especially in high-risk families.


Atrial fibrillation-induced cardiac troponin I release.
Cardiac troponin I (cTnI) is highly specific for myocardial damage and for the diagnosis of acute coronary syndrome. We investigated cTnI utility and predictive value in patients with atrial fibrillation (AF) in the acute setting. We studied 354 consecutive patients with the primary diagnosis of AF and clinical symptoms suggestive of myocardial ischemia presenting to our emergency department. cTnI was obtained on presentation. Patients with ST-segment elevation myocardial infarction were excluded. Coronary angiography was performed in 100 patients. cTnI was elevated (>0.09 μg/L) in 51 of 354 (15%) patients. The mean cTnI in these patients was 0.37 μg/L (0.09-3.14). In 23 of 100 patients undergoing coronary angiography, cTnI was elevated. Only 6 of these 23 patients (26%) had significant stenosis. In 77 of 100 patients undergoing coronary angiography, cTnI was normal, revealing significant stenosis in 25 patients (33%). The positive predictive value of elevated cTnI for a coronary intervention was 26% and the negative predictive value was 68%. Using multivariate logistic regression, we found that heart rate on presentation, the presence of angina pectoris, left ventricular ejection fraction, serum creatinine, and hemoglobin independently predicted elevated cTnI level. These data are the first to show that AF in the acute setting is frequently associated with cTnI elevations. AF patients with high heart rate and/or angina pectoris often show false elevated cTnI levels. These findings are relevant for clinicians evaluating patients with acute AF and myocardial ischemia symptoms. Appropriate clinical guidelines must be established that also consider AF-related elevations in cTnI.


Moderating effects of music on resting state networks.
Resting state networks (RSNs) are spontaneous, synchronous, low-frequency oscillations observed in the brains of subjects who are awake but at rest. A particular RSN called the default mode network (DMN) has been shown to exhibit changes associated with neurological disorders such as temporal lobe epilepsy or Alzheimer's disease. Previous studies have also found that differing experimental conditions such as eyes-open versus eyes-closed can produce measurable changes in the DMN. These condition-associated changes have the potential of confounding the measurements of changes in RSNs related to or caused by disease state(s). In this study, we use fMRI measurements of resting-state connectivity paired with EEG measurements of alpha rhythm and employ independent component analysis, undirected graphs of partial spectral coherence, and spatiotemporal regression to investigate the effect of music-listening on RSNs and the DMN in particular. We observed similar patterns of DMN connectivity in subjects who were listening to music compared with those who were not, with a trend toward a more introspective pattern of resting-state connectivity during music-listening. We conclude that music-listening is a valid condition under which the DMN can be studied.


Targeting Type 2 Inflammation and Epithelial Alarmins in Chronic Obstructive Pulmonary Disease: A Biologics Outlook.
Chronic obstructive pulmonary disease (COPD) is a complex, heterogeneous, progressive inflammatory airway disease associated with a significant impact on patients' lives, including morbidity and mortality, and significant healthcare costs. Current pharmacologic strategies, including first- and second-line therapies such as long-acting β2-agonists, long-acting muscarinic antagonists, inhaled corticosteroids, phosphodiesterase-4 inhibitors, and macrolides, provide relief to patients with COPD. However, many patients remain symptomatic, with persistent symptoms and/or acute exacerbations and progressive lung function loss. Although neutrophilic inflammation is the most common type of inflammation in COPD, 20-40% of patients with COPD exhibit type 2 inflammation, with roles for CD4+ (cluster of differentiation 4) T-helper cell type 1 cells, type 2 innate lymphoid cells, eosinophils, and alternatively activated macrophages. On the basis of the current limitations of available therapies, a significant unmet need exists in COPD management, including the need for targeted therapies to address the underlying pathophysiology leading to disease progression, such as type 2 inflammation, as well as biomarkers to help select the patients who would most benefit from the new therapies. Significant progress is being made, with evolving understanding of the pathobiology of COPD leading to novel therapeutic targets including epithelial alarmins. In this review, we describe the current therapeutic landscape in COPD, discuss unmet treatment needs, review the current knowledge of type 2 inflammation and epithelial alarmins in COPD, explore potential biomarkers of type 2 inflammation in COPD, and finally provide a rationale for incorporating therapies targeting type 2 inflammation and epithelial alarmins in COPD. Video Abstract available online at www.atsjournals.org.


Rapid and Safe Crossing of the Chasm: Application of a Flipped Learning Framework for the Clipping Over the Scope Technique.
Training practicing physicians to adopt new technology may be difficult because most endoscopy training is given during fellowship training. As such, the adoption of new technology in gastroenterology is typically slow. We designed our course to train our cohort of practicing physicians using flipped learning, a pedagogical approach in which instructional cognitive content is delivered to the individual instead of the group, usually through online platforms and outside of the classroom. We describe our methods and results of the training courses on the techniques of clipping over the scope for gastrointestinal bleeding and endoscopic balloon dilation.


Production of human caseinomacropeptide in recombinant Saccharomyces cerevisiae and Pichia pastoris.
Caseinomacropeptide is a polypeptide of 64 amino acid residues (106-169) derived from the C-terminal part of the mammalian milk k-casein. This macropeptide has various biological activities and is used as a functional food ingredient as well as a pharmaceutical compound. The gene encoding the human caseinomacropeptide (hCMP) was synthesized and expressed with an alpha-factor secretion signal in the two yeast strains, Saccharomyces cerevisiae and Pichia pastoris. The complete polypeptide of the recombinant hCMP was produced and secreted in a culture medium by both the strains, but the highest production was observed in S. cerevisiae with a galactose-inducible promoter. In a fed-batch bioreactor culture, 2.5 g/l of the recombinant hCMP was obtained from the S. cerevisiae at 97 h.


The sartorius muscle: anatomic considerations for reconstructive surgeons.
To evaluate the sartorius muscle as an alternative donor site for functional transfer, the neurovascular anatomy of the muscle was studied in 42 human sartorius muscle specimens (22 fresh and 20 preserved). Eleven adult fresh cadavers were injected with a mixture of lead oxide, gelatin and water (200 ml/kg) through the common carotid and femoral arteries. The sartorius muscle with its neurovascular pedicles was dissected, and radiographed. The sartorius muscle was also dissected out in 10 preserved cadavers. The neurovascular anatomy was thus analyzed in 42 sartorius muscles. The results show that each nerve supplying the sartorius muscle is accompanied by one vascular pedicle, forming a neurovascular hilum. Within the muscle, most of the nerves and vessels divide early, and their branches run parallel to each other and to the muscle fibers. Many of the vessels anastomose with each other to form an intricate vascular network. We conclude that it is possible to subdivide the muscle into functional units to harvest a segmental muscle flap with a neurovascular pedicle for transfer.


Sox10 Is a Specific Biomarker for Neural Crest Stem Cells in Immunohistochemical Staining in Wistar Rats.
Neural crest stem cells (NCSCs) are prototypically migratory cells immigrating from the dorsal neural tube to specific embryonic sites where they generate a variety of cell types. A lot of biomarkers for NCSCs have been identified. However, which biomarkers are the most specific is still unclear. The rat embryos harvested in embryonic day 9 (E9), E9.5, E10, E10.5, E11, E12, E13, and E14 were paraffin-embedded and sectioned in transverse. NCSCs were spatiotemporally demonstrated by immunohistochemical staining with RET, p75NTR, Pax7, and Sox10. NCSCs were isolated, cultured, and stained with RET, p75NTR, Pax7, and Sox10. In the paraffin sections of rat embryos, the immunohistochemical staining of RET, p75NTR, and Sox10 can all be used in demonstrating NCSCs. Sox10 was positive mainly in NCSCs while RET and p75NTR were positive not only in NCSCs but also in other tissue cells. In primary culture cells, Sox10 was mainly in the nucleus of NCSCs, RET was mainly in the membrane, and p75NTR was positive in cytoplasm and membrane. Sox10 is the specific marker for immunohistochemical staining of NCSCs in paraffin sections. In cultured cells, Sox10, p75NTR, and RET presented a similar staining effect.


G2 repair and aging: influence of donor age on chromosomal aberrations in human lymphocytes.
The caffeine effects on chromosomal aberration frequency and mean G2 duration were studied in human lymphocytes in vitro from three age groups of normal donors (I: 1-5 years old; II: 30-40 years old; III: 60-70 years old). Under control conditions, the three age groups showed a similar frequency of chromosomal aberrations. All three age groups exhibited a linear dose response for aberrations with caffeine treatments. However, lymphocytes from aged individuals (groups II and III) showed higher chromosomal aberration frequencies and longer G2 duration than cells from young individuals (group I). The caffeine effect in reducing G2 length was rather similar in every age group. The reversion of caffeine effects by adenosine or niacinamide in lymphocytes from older individuals was higher than in cells from group I. The different caffeine effects and G2 values between lymphocytes from old and young individuals are most likely due to a higher number of DNA lesions reaching G2 phase and/or a decrease of the G2 repair capability of lymphocytes from older individuals.


Global gene expression analysis revealed an unsuspected deo operon under the control of molybdate sensor, ModE protein, in Escherichia coli.
ModE protein, a molybdate sensor/regulator, controls the transcription of genes coding for molybdate uptake (mod), molybdopterin synthesis (moa), molybdoenzymes nitrate reductase (nap) and dimethylsulfoxide reductase (dms), as well as fermentative dihydrogen production (fdhF and hyc) and respiratory nitrate reductase (narXL) in Escherichia coli. The catalytic product of a second protein, MoeA, is also required for molybdate-dependent positive regulation of hyc and nar operons. To explore the potential role of ModE and MoeA in the regulation of other E. coli genes, the global gene expression profile of a wild type and a modE, moeA double mutant grown in glucose-minimal medium under anaerobic conditions were compared. Expression of 67 genes was affected by the modE and moeA mutations (P value <0.01). Of these, 17 differed by at least 2-fold or higher. Fourteen genes were expressed at a higher level in the mutant (2.4- to 23.9-fold) (notably, mod-molybdate transport, deo-nucleoside catabolism and opp-oligopeptide transport operons) and dmsA and yli operon were expressed at a higher level in the wild type parent (2.6- to 5.7-fold). One of the unexpected findings was repression of the deo operon by ModE. This was confirmed by quantitative RT-PCR and by the analysis of a deoC-lacZ fusion. The deo promoter/operator region contains a putative ModE-consensus sequence centered at -35 in which the adenines are replaced by guanines (TGTGT-N7-TGTGT). The ModE protein did bind to the deo upstream DNA and shifted its electrophoretic mobility. Bioinformatics analysis of the E. coli genome for ModE-consensus motif (TATAT-N7-TAYAT) identified 21 additional genes/operons including the moa as potential targets for Mo-control. The physiological role of many of the genes identified solely by bioinformatics (19/21) is unknown. Expression levels of these genes were similar in the parent and the isogenic modE, moeA mutant when cultured anaerobically in glucose-minimal medium. This study identified additional targets, such as deo and opp, for the Mo-dependent control in E. coli.


Cross-cultural epidemiology.
Two issues led me into the area of cross-cultural psychiatric epidemiology in the 1980s. The National Institute of Mental Health funded the Epidemiological Catchment Area Studies. One of them included a study of a Caucasian and Hispanic populations in Los Angeles. Dr Masaaki Kato, then the Director of the National Institute of Mental Health of Japan, was the consultant for a JAICA-funded project in Lima, Peru. He was interested in fostering psychiatric research there, so I suggested an epidemiological study. This study was done in two phases with Drs Shunichiro Hayashi, Kimpei Minobe and Alberto Perales. Because it is extraordinarily expensive to undertake epidemiological studies in the USA, I met with colleagues regarding psychiatric epidemiological studies in Asia, Dr Chung-kyoon Lee at the Seoul National University in Korea, Dr Eng-Kung Yeh of the National Taiwan University in Taipei,Taiwan, Dr Char-nie Chen of the Chinese University of Hong Kong, and Dr Masaaki Kato in Japan. Studies have been completed in Korea, Taiwan, Hong Kong, but not in Japan. In the meantime, very small pilot studies among Asian groups in Los Angeles were performed. The very recent results of the study of Chinese in Los Angeles, California, with the Composite International Diagnostic Interview are now available to compare the prevalence of selected psychiatric disorders among the Chinese in Los Angeles and the data from the National Co-Morbidity Study.


Identifying Accessibility Requests for Patients With Disabilities Through an Electronic Health Record-Based Questionnaire.
People with disabilities experience disparities in health care access and outcomes, and inaccessible health care facilities are major barriers to health care access. Methods to collect accessibility request information are needed to improve health care outcomes for patients with disabilities. To evaluate an electronic health record (EHR)-based questionnaire designed to identify accessibility requests for patients with disabilities at an eye clinic. This cross-sectional pilot study implemented an EHR questionnaire and prospectively collected data on accessibility requests at a university-based eye clinic. The study included 55 722 patients making appointments at the Johns Hopkins Wilmer Eye Institute from April 1, 2019, to March 31, 2020. The Wilmer Eye Institute staff were trained to assess accessibility requests of patients making appointments in-person or via telephone using a standardized script and entering patient responses into the EHR. Data were later extracted for analysis and used to determine the proportion of patients making eye appointments who reported a disability accessibility request (physical, sensory, or intellectual) during their clinic visit. Accessibility request data were collected from 250 932 patient encounters. Patients had a mean (SD) age of 61.9 (20.6) years; most were women (146 846 [58.5%]) and were White individuals (162 720 [64.9%]). Of these, 23 510 (9.4%) encounters were associated with an accessibility request. The most reported accessibility request was mobility related (18 857 [7.5%]) (needing a cane, crutches, motorized scooter, walker, wheelchair, stretcher, assistance standing, or transport services), followed by sensory-related (2988 [1.2%]) (visual, hearing, or speech impairment), intellectual (353 [0.1%]), and other (1312 [0.5%]) (assistance with filling forms or service animal) requests. Patients with an accessibility request compared with those without, were older (72.6 vs 60.8 years), less likely to be White individuals (59.7% vs 65.4%), and more likely to be women (62.6% vs 58.1%), receiving Medicare (69.6% vs 41.5%), and have vision impairment (41.3% vs 13.6%) (P < .001 for all). In this cross-sectional study, a substantial proportion of patients making eye appointments reported having accessibility requests as captured using a new EHR-based questionnaire. Such standardization of data collection for disability-related accessibility requests in EHR is scalable, could be expanded to other clinical settings, and has the potential to improve accessibility of health care interactions for patients with disabilities.


Morphological and functional alterations of the cochlea in apolipoprotein E gene deficient mice.
The relationship between hyperlipidemia and sensorineural hearing loss remains obscure. In this study, we elucidate for the first time the cochlear morphological and auditory alterations and their relationships with hyperlipidemia, atherosclerosis, and endothelial dysfunction in apolipoprotein-E knockout (ApoE-KO) mice. Ten-week-old ApoE-KO mice were fed either atherosclerotic diet (1.25% cholesterol) or normal diet. Wild type mice (C57BL/6J) served as normal controls. Fourteen weeks later, marked hyperlipidemia, atherosclerosis, endothelial dysfunction, and hearing impairment, especially in the high frequencies, had developed in ApoE-KO mice as compared with C57BL/6J mice (P<0.001). A high positive correlation between hearing loss and the extent of atherosclerosis and plasma total cholesterol levels was found. Hearing loss, especially at high frequencies, was detected in all ApoE-KO mice. Hair cell loss mainly at the base turn, thickening of vascular intima, and lumen stenosis of the spiral modiolar artery (SMA) in cochlea were also found; these histological changes were exacerbated by the atherosclerotic diet. Furthermore, endothelial nitric oxide synthase (eNOS) in aortic wall and cochlea was distinctly reduced in ApoE-KO mice. These results demonstrate that hyperlipidemia and atherosclerosis can induce alterations in cochlear morphology and function. The stenosis of SMA, which may cause cochlear ischemia and hypoxia, endothelial dysfunction, and low eNOS activity, may contribute to hearing loss.


Cardiorespiratory monitoring in the delivery room using transcutaneous electromyography.
To assess feasibility of transcutaneous electromyography of the diaphragm (dEMG) as a monitoring tool for vital signs and diaphragm activity in the delivery room (DR). Prospective observational study. Delivery room. Newborn infants requiring respiratory stabilisation after birth. In addition to pulse oximetry (PO) and ECG, dEMG was measured with skin electrodes for 30 min after birth. We assessed signal quality of dEMG and ECG recording, agreement between heart rate (HR) measured by dEMG and ECG or PO, time between sensor application and first HR read-out and agreement between respiratory rate (RR) measured with dEMG and ECG, compared with airway flow. Furthermore, we analysed peak, tonic and amplitude diaphragmatic activity from the dEMG-based respiratory waveform. Thirty-three infants (gestational age: 31.7±2.8 weeks, birth weight: 1525±661 g) were included.18%±14% and 22%±21% of dEMG and ECG data showed poor quality, respectively. Monitoring HR with dEMG was fast (median 10 (IQR 10-11) s) and accurate (intraclass correlation coefficient (ICC) 0.92 and 0.82 compared with ECG and PO, respectively). RR monitoring with dEMG showed moderate (ICC 0.49) and ECG low (ICC 0.25) agreement with airway flow. Diaphragm activity started high with a decreasing trend in the first 15 min and subsequent stabilisation. Monitoring vital signs with dEMG in the DR is feasible and fast. Diaphragm activity can be detected and described with dEMG, making dEMG promising for future DR studies.


Enthalpies of formation and bond dissociation energies of lower alkyl hydroperoxides and related hydroperoxy and alkoxy radicals.
The enthalpies of formation and bond dissociation energies, D(ROO-H), D(RO-OH), D(RO-O), D(R-O 2) and D(R-OOH) of alkyl hydroperoxides, ROOH, alkyl peroxy, RO, and alkoxide radicals, RO, have been computed at CBS-QB3 and APNO levels of theory via isodesmic and atomization procedures for R = methyl, ethyl, n-propyl and isopropyl and n-butyl, tert-butyl, isobutyl and sec-butyl. We show that D(ROO-H) approximately 357, D(RO-OH) approximately 190 and D(RO-O) approximately 263 kJ mol (-1) for all R, whereas both D(R-OO) and D(R-OOH) strengthen with increasing methyl substitution at the alpha-carbon but remain constant with increasing carbon chain length. We recommend a new set of group additivity contributions for the estimation of enthalpies of formation and bond energies.


Tyramine Acts Downstream of Neuronal XBP-1s to Coordinate Inter-tissue UPRER Activation and Behavior in C. elegans.
In C. elegans, expression of the UPRER transcription factor xbp-1s in neurons cell non-autonomously activates the UPRER in the intestine, leading to enhanced proteostasis and lifespan. To better understand this signaling pathway, we isolated neurons from animals expressing neuronal xbp-1s for transcriptomic analysis, revealing a striking remodeling of transcripts involved in neuronal signaling. We then identified signaling molecules required for cell non-autonomous intestinal UPRER activation, including the biogenic amine tyramine. Expression of xbp-1s in just two pairs of neurons that synthesize tyramine, the RIM and RIC interneurons, induced intestinal UPRER activation and extended longevity, and exposure to stress led to splicing and activation of xbp-1 in these neurons. In addition, we found that neuronal xbp-1s modulates feeding behavior and reproduction, dependent upon tyramine synthesis. XBP-1s therefore remodels neuronal signaling to coordinately modulate intestinal physiology and stress-responsive behavior, functioning as a global regulator of organismal responses to stress.


Variation of photosynthesis, secondary metabolites and antioxidant activities in third generation of spaceflight-induced Salvia miltiorrhiza.
Spaceflight has long been perceived as an effective way to improve the quantity and quality of plants with wide applications. In order to obtain stable and inheritable descendants of spaceflight-induced Salvia miltiorrhiza lines, we investigated and analyzed four lines m16, m50, m51, m57 (three individuals of each line) and the ground control (three individuals) of the third generation of spaceflight-induced S. miltiorrhiza from primary/secondary metabolism and antioxidative abilities. A portable photosynthesis system (Li-6400) with red/blue LED light source was used to perform the photosynthetic characteristics to evaluate their primary productivity. The secondary metabolites (phenolic acids, tanshinones, total phenolics and flavonoids) and antioxidant activity of roots were analyzed to assess their quality. Compared with control, line m16 presented weak photosynthetic ability, but high apparent quantum yield (AQY), higher contents of secondary metabolites, and stronger antioxidative abilities. Line m57 had a strong gas exchange ability, relatively higher secondary metabolites contents, and ascending antioxidative abilities. Lines m50 and m51 were in the middle level of lines m16 and m57. The principal component analysis for all the original data revealed three components including a root-related index, a leaf-related index, and a CO2 response parameter could be used to distinguish spaceflight-induced S. miltiorrhiza lines. Line m57 could be an appropriate material for the investigation of targeted breeding towards high production, and line m16 could be used to identify essential genes and unravel sophisticated pathways underlying the secondary metabolisms.


[Effects of triptolide on anti-angiogenesis by reducing expression of urokinase plasminogen activator].
In order to unveil the anti-angiogenic mechanism of triptolide, we investigated the effects of triptolide on the proliferation, migration, angiogenesis and u-PA expression of cultured HUVECs. MTT assay found that triptolide could inhibit the proliferation of HUVECs, and three-dimensional culture system revealed that triptolide could curb the migration of HUVECs. The chick embryo chorioallantoic membrane (CAM) test showed that triptolide could inhibit angiogenesis. Real time quantitive RT-PCR showed the expression of u-PA of HUVECs was down-regulated by triptolide. Therefore, triptolide may inhibit the proliferation and migration of endothelial cell by way of reducing the expression of u-PA. These findings may conduce to the elucidation of the anti-angiogenic mechanism of triptolide.


Life-course socioeconomic circumstances in acute, chronic and disabling pain among young employees: a double suffering.
Pain is known to be socioeconomically patterned and associated with disability. However, knowledge is scarce concerning life-course socioeconomic circumstances and pain among young adults. Our aim was to examine the associations of childhood and current socioeconomic circumstances with acute pain and chronic pain with low and high disability levels among young Finnish municipal employees. We analysed questionnaire data retrieved from the Young Helsinki Health Study (n=4683) covering 18-39-year-old employees of the City of Helsinki, Finland. We included multiple indicators of childhood and current socioeconomic circumstances and examined their associations with acute pain and with chronic pain with low and high disability levels. The level of chronic pain-related disability was assessed by the chronic pain grade questionnaire. Multinomial logistic regression analyses were conducted with stepwise adjustments for sociodemographic, socioeconomic and health-related covariates. Childhood and current socioeconomic disadvantage were associated with acute and chronic pain, particularly with chronic pain with high disability level. The strongest associations after adjustments for covariates remained between chronic pain with high disability level and low educational level (odds ratio (OR) 3.38, 95% confidence interval (CI) 2.18-5.24), manual occupation (OR 3.75, 95% CI 1.92-7.34) and experiencing frequent economic difficulties (OR 3.07, 95% CI 2.00-4.70). Pain is a common complaint that contributes to disability among young employees, particularly the most socioeconomically vulnerable. There is a socioeconomic gradient in both pain chronicity and the level of chronic pain-related disability. Life-course socioeconomic factors should be considered in pain-preventing strategies and in clinical practice.


HIV-related services for persons with severe mental illness: policy and practice in New Hampshire community mental health.
Rates of HIV and HIV risk behaviors are elevated among people with severe mental illnesses (SMI). Little is known about the extent to which community mental health (CMH) centers screen, refer, and educate their clients regarding HIV and sexually transmitted diseases (STDs). The authors surveyed CMH administrators and clinicians in New Hampshire regarding HIV/STD policy, practices, knowledge, and attitudes. HIV/STD service availability varied, and the amount of services provided was unrelated to the prevalence of HIV and AIDS in that region. Clinicians were knowledgeable about general HIV information but lacked specific knowledge about HIV related to persons with SMI. CMH staff had positive attitudes about helping clients with HIV issues. Administrators were interested in receiving training. Policy leadership, CMH practice guidelines, and training are warranted in light of the pressing public health implications of HIV/STDs among people with SMI.


The use of artificial neural network for modelling of phycoremediation of toxic elements As(III) and As(V) from wastewater using Botryococcus braunii.
In the present study, a thorough investigation has been done on the removal efficiency of both As(III) and As (V) from synthetic wastewater by phycoremediation of Botryococcus braunii algal biomass. Artificial neural networks (ANNs) are practised for predicting % phycoremediation efficiency of both As(III) and As(V) ions. The influence of several parameters for example initial pH, inoculum size, contact time and initial arsenic concentration (either As(III) or As(V)) was examined systematically. The maximum phycoremediation of As(III) and As(V) was found to be 85.22% and 88.15% at pH9.0, equilibrium time of 144h by using algal inoculum size of 10% (v/v) and initial arsenic concentration of 50mg/L. The data acquired from laboratory scale experimental set up was utilized for training a three-layer feed-forward back propagation (BP) with Levenberg-Marquardt (LM) training algorithm having 4:5:1 architecture. A comparison between the experimental data and model outputs provided a high correlation coefficient (R(2)all_ANN equal to 0.9998) and exhibited that the model was capable for predicting the phycoremediation of both As(III) and As(V) from wastewater. The network topology was optimized by changing number of neurons in hidden layers. ANNs are efficient to model and simulate highly non-liner multivariable relationships. Absolute error and Standard deviation (SD) with respect to experimental output were calculated for ANN model outputs. The comparison of phycoremediation efficiencies of both As(III) and As(V) between experimental results and ANN model outputs exhibited that ANN model can determine the behaviour of As(III) and As(V) elimination process under various circumstances.


Adolescent/Young Adult Long-Acting Reversible Contraception: Experience from a Multisite Adolescent Medicine Collaborative.
To report on long-acting reversible contraception (LARC) experience and continuation rates in the Adolescent Medicine LARC Collaborative. LARC insertion data (682 implants and 681 intrauterine devices [IUDs]) were prospectively collected from January 1, 2017, through December 31, 2019, across 3 Adolescent Medicine practices. Follow-up data through December 31, 2020, were included to ensure at least 1 year of follow-up of this cohort. Continuation rates were calculated at 1, 2, and 3 years, overall and by Adolescent Medicine site, as were descriptive statistics for LARC procedural complications and patient experience. Implant and IUD insertion complications were uncommon and largely self-limited, with no IUD-related uterine perforations. Uterine bleeding was the most frequently reported concern at follow-up (35% implant, 25% IUD), and a common reason for early device removal (45% of implant removals, 32% of IUD removals). IUD malposition or expulsion occurred following 6% of all insertions. The pooled implant continuation rate at 1 year was 87% (range, 86%-91% across sites; P = .63), 66% at 2 years (range, 62%-84%; P = .01), and 42% at 3 years (range, 36%-60%; P = .004). The pooled IUD continuation rate at 1 year was 88% (range, 87%-90% across sites; P = .82), 77% at 2 years (range, 76%-78%; P = .94), and 60% at 3 years (range, 57%-62%; P = .88). LARC is successfully provided in Adolescent Medicine clinical settings, with continuation rates analogous to those of well-resourced clinical trials. Uterine bleeding after LARC insertion is common, making counselling imperative. Future analyses will assess whether the medical management of LARC-related nuisance bleeding improves continuation rates in our Adolescent Medicine patient population.


Mathematical model of COVID-19 transmission dynamics incorporating booster vaccine program and environmental contamination.
COVID-19 is one of the greatest human global health challenges that causes economic meltdown of many nations. In this study, we develop an SIR-type model which captures both human-to-human and environment-to-human-to-environment transmissions that allows the recruitment of corona viruses in the environment in the midst of booster vaccine program. Theoretically, we prove some basic properties of the full model as well as investigate the existence of SARS-CoV-2-free and endemic equilibria. The SARS-CoV-2-free equilibrium for the special case, where the constant inflow of corona virus into the environment by any other means, Ω is suspended ( Ω = 0 ) is globally asymptotically stable when the effective reproduction number R 0 c < 1 and unstable if otherwise. Whereas in the presence of free-living Corona viruses in the environment ( Ω > 0 ), the endemic equilibrium using the centre manifold theory is shown to be stable globally whenever R 0 c > 1 . The model is extended into optimal control system and analyzed analytically using Pontryagin's Maximum Principle. Results from the optimal control simulations show that strategy E for implementing the public health advocacy, booster vaccine program, treatment of isolated people and disinfecting or fumigating of surfaces and dead bodies before burial is the most effective control intervention for mitigating the spread of Corona virus. Importantly, based on the available data used, the study also revealed that if at least 70% of the constituents followed the aforementioned public health policies, then herd immunity could be achieved for COVID-19 pandemic in the community.


Immunocytochemical reaction of Ca1 and HMFG2 monoclonal antibodies with cells from serous effusions.
The Ca1 antibody was used in an alkaline phosphatase immunocytochemical method on cells obtained from 150 specimens of pleural and ascitic fluids. The results were compared with the routine cytology report based on the light microscopical appearances. The Ca1 antibody identified tumour cells in 51 of 57 specimens with malignant cells. The exceptions were four small cell carcinomas, one malignant lymphoma, and one adenocarcinoma. A further seven specimens reported as containing atypical cells but without conclusive evidence of malignancy were Ca1 positive. The Ca1 antibody did not give a positive reaction with benign mesothelial cells. Similar results were obtained with the HMFG2 antibody and malignant cells, but in eight of 18 benign effusions it reacted with mesothelial cells.


Cancer and stigma: experience of patients with chemotherapy-induced alopecia.
Chemotherapy-induced alopecia is one of the most distressing side-effects of chemotherapy. In this article we examine how patients react to hair loss due to chemotherapy; for women in particular, the reaction involves a confrontation with the lethal nature of cancer, whilst for men it is a normal and inevitable consequence of treatment. We then analyse the strategies used to cope with alopecia. One strategy involves camouflaging and hiding; the patients wear wigs in an attempt to partially or completely hide their hair loss. Another strategy is to treat it as commonplace: wearing a wig is played down and banalised. Sometimes this can take the form of provocation, in which case baldness is seen as the symbol of the cancer patient's new identity.


Seeing beyond COVID-19: understanding the impact of the pandemic on oncology, and the importance of preparedness.
The impact of this pandemic is not only through COVID-19 itself: the care for non-COVID-19 related conditions has been dramatically curtailed, shaking entire healthcare services around the world. Amongst the non-COVID-19 related conditions, oncology has been disproportionally affected. We discuss how oncology has changed since the acute phase of the pandemic; its impact on clinicians, trainees, and patients; and offer some medical and historical perspectives to reflect on how this impact could be reduced.


Analysis of craniectomy bone flaps stored in a neurosurgical cryopreservation freezer: microorganism culture results and reimplantation rates.
Cryopreservation of bone flaps after decompressive craniectomies is a common practice. A frequent complication after bone flap reimplantation is postoperative infection, so culturing of frozen craniectomy bone flaps is a crucial practice that can prevent patient morbidity and mortality. Although many studies report on infection rates after cranioplasty, no study reports on the results of bone flaps stored in a cryopreservation freezer, reimplanted or otherwise. We sought to analyze the flaps in our medical center's bone bank freezer, including microorganism culture results and reimplantation rates of cryopreserved bone flaps. Patients who underwent craniectomy and had bone flaps cryopreserved between January 1, 2016, and July 1, 2022, were included in this retrospective study. Information about bone flap cultures and reimplantation or discard was obtained from a prospectively maintained cryopreservation database. Information including infection rates and mortality was acquired from a retrospective review of patient records. Culture results were obtained for all flaps immediately before cryopreservation and again at the time of reimplantation at the operator's discretion. There were 148 bone flaps obtained from 145 patients (3 craniectomies were bilateral) stored in our center's freezer. Positive culture results were seen in 79 (53.4%) flaps. The most common microorganism genus was Propionibacterium with 47 positive flaps, 46 (97.9%) of which were P. acnes. Staphylococcus was the second most common with 23 positive flaps, of which 8 (34.8%) tested positive for S. epidermidis. Of the 148 flaps, 25 (16.9%) were reimplanted, 116 (78.4%) were discarded, and 7 (4.7%) are still being stored in the freezer. Postcranioplasty infections were seen in 3 (12%) patients who had flap reimplantation. Considering the substantial number of positive cultures and limited reimplantation rate, we have reservations about the logistical efficiency of cryopreservation for flap storage. Future multicenter studies analyzing reimplantation predictors could help to reduce unnecessary freezing and culturing.


Growth-stimulating effect of transferrin on a hybridoma cell line: relation to transferrin iron-transporting function.
The relation of the growth-stimulating capacity of transferrin to its iron-transporting function was investigated in mouse hybridoma PLV-01 cells cultivated in a chemically defined medium. The cells were precultivated in protein-free medium supplemented either with ferric citrate (cells with a high intracellular iron level) or with iron-saturated transferrin (cells with a low intracellular iron level). Iron uptake was monitored after the application of 59Fe-labeled ferric citrate or pig transferrin. Cultivation of the cells at the optimum growth-stimulating concentration (500 microM) of ferric citrate resulted in an intracellular iron level about 100-fold higher than that of cells cultivated at the optimum transferrin concentration (5 micrograms/ml). Replacement of pig transferrin with bovine transferrin resulted in similar intracellular iron levels, but the growth-stimulating effect of bovine transferrin was more than one order of magnitude lower. Cells with a high intracellular iron level grew equally well when cultivated with iron-saturated transferrin or with apotransferrin + deferoxamine (2 micrograms/ml). On the other hand, cells with a low intracellular iron level required iron-saturated transferrin for further growth and apotransferrin + deferoxamine was ineffective. The results suggest that transferrin can act as a cell growth factor only in the iron-saturated form. However, several findings of this work indicate that supplying cells with iron cannot be accepted as the full explanation of the transferrin growth-stimulating effect.


Calyculin A modulates activation of the NADPH-oxidase in Me2SO-differentiated HL-60 cells.
Human promyelocytic leukemia cells (HL-60) have been used as a model system in which to study the effects of protein phosphatase inhibitors on NADPH-oxidase activation. Since O2- is generated by NADPH-oxidase, we examined the effect of calyculin A pretreatment on oxidase activation in response to various agonists. When Me2SO-differentiated HL-60 cells were treated with calyculin A prior to the addition of phorbol 12-myristate 13-acetate (PMA), O2- production was inhibited; however, calyculin A enhanced O2- production by N-formyl-methionyl-leucyl-phenylalanine (FMLP). The decreased O2- production seen with calyculin A pretreatment followed by PMA may be due to diminished translocation of the p47-phox and p67-phox, cytosolic components of the oxidase, and inhibition of arachidonic acid release. Interestingly calyculin A pretreatment followed by either agonist significantly enhanced mitogen-activated-protein kinase (MAPK) activity. The differential effects of pretreatment with calyculin A on subsequent oxidase stimulation elicited by FMLP or PMA provide further evidence for substantial heterogeneity in the activation of the respiratory burst.


A History of the Origin and Development of Japanese Society for Neurochemistry: International Cooperation to Overcome Dementia and Mental Illness.
"Neurochemistry" in Japan was established by intensive cooperation between psychiatrists and their collaborators, biochemists, who have sought to investigate the etiology of mental illness to establish treatments. It was a completely different direction from the flow of modern biochemistry that was born using microorganisms or eukaryotic cells as research materials. Neurochemists aimed to elucidate the physiological or pathological functions of the brain through chemical analysis of the morphologically and functionally unique complexity and characteristics of brain. I here describe some of the origin and history of neurochemistry in Japan how researchers estabIished Japanese Society for Neurochemistry in1958 Yasuzo Tsukada as a president in collaboration with Isamu Sano, Genkichiro Takagaki and Masanori Kurokawa. The formation of research groups with the support of MEXT played a major role in promoting neurochemistry. Many international conferences held in Japan promoted the activity of neurochemistry: The International Society of Physiology (Tokyo) in 1965, and the Japan-US Neurochemistry Conference (Oiso) in 1965, and in 1967 the International Conference on Biochemistry (Tokyo). These meetings offered excitements to younger researchers by close interaction with the world top class researchers. Government established Brain Research Institutes in several national universities. The Asia-Pacific Society for Neurochemistry (APSN) was established in 1991 subsequent to an initiative by JSN. APSN presidents: Yasuzo Tsukada, Kazuhiro Ikenaka, and Akio Wanaka contributed to promote neurochemistry. The 4th ISN meeting was organized at Tokyo (Yasuzo Tsukada, president) in 1973 and the 15th ISN meeting at Kyoto (Kinya Kuriyama, president) in 1995. Kunihiko Suzuki and Kazuhiro Ikenaka as ISN Presidents greatly contributed in promoting the activity of ISN.


[Clinical significance of MRP8 and cypA expression in laryngeal squamous cell carcinoma tissues].
To study differential expression of MRP8, CypA protein in the patients of laryngeal squamous cell carcinoma (LSCC) and the relationship in the development of LSCC. Immunohistochemistry was used to detect the expression of MRP8,CypA protein in LSCC tissues of 41 cases and matched paraneoplastic normal tissues of 41 cases,with results compared to the clinical data to determine significance. The expression of MRP8, CypA protein in carcinoma and normal tissues and composition of different positive grades were in statistical significance (P < 0.01). The expression levels of MRP8 were no significant correlations were identified against any parameter (age,sex and cervical lymphatic metastasis) examined (P > 0.05), but related to pathological stage (P < 0.05). MRP8 protein is on intimate terms with different pathological differentiation stage of LSCC. MRP8, CypA protein may play an important role in the development and progression of LSCC.


A histomorphometric study of bone changes in thyroid dysfunction in rats.
Clinical studies in thyrotoxicosis reveal a state of high bone turnover leading, eventually, to osteoporosis. Recently there has been concern that thyroxine (T4) treatment may have a similar effect on bone. Rat models have been used to study the effects of T4 on bone, but the majority of studies have looked at the effects of T4 after only 3 weeks of treatment. The aim of this study was to evaluate histomorphometric changes in rats after 12 weeks of thyroxine overtreatment or 12 weeks of hypothyroidism compared with untreated control animals. Animals received either T4 200 micrograms/kg per day, 0.1% propylthiouracil, or vehicle for 12 weeks. Tetracycline was administered 1 week and 3 weeks prior to killing. Iliac crest bone was used for histomorphometry. Serum T4 measurements (taken at killing) confirmed hyper- and hypothyroidism in the appropriate animal groups (between group difference p < 0.001 by ANOVA). In hyperthyroid animals there was an increase in mineral apposition rate (MAR; 0.94 vs. 0.59 microns/day, p < 0.001) and mineral formation rate (MFR/BS; 0.24 vs. 0.12 x 10(-2) micron3/micron2 per day, p < 0.001) and a slight increase in eroded surfaces (ES/BS%; 1.54 vs. 1.36, p < 0.05) compared with controls, consistent with previous in vitro and in vivo observations. In hypothyroid rats there was a marked reduction in osteoid surfaces (OS/BS%; 1.7 vs. 24.8, p < 0.001) and MAR (0.3 vs. 0.59 micrograms/day, p < 0.001), a reduction in ES/BS% (0.51 vs. 1.36, p < 0.05), and an increase in cancellous bone volume (BV/TV%; 30.29 vs. 19.6, p < 0.05), suggesting that thyroid hormones are a requirement for normal bone turnover.(ABSTRACT TRUNCATED AT 250 WORDS)


Delineating the Effects of Passaging and Exposure in a Longitudinal Study of Arsenic-Induced Squamous Cell Carcinoma in a HaCaT Cell Line Model.
Cutaneous squamous cell carcinoma (cSCC) is a major deleterious health effect of chronic arsenic (iAs) exposure. The molecular mechanism of arsenic-induced cSCC remains poorly understood. We recently demonstrated that chronic iAs exposure leads to temporally regulated genome-wide changes in profiles of differentially expressed mRNAs and miRNAs at each stage of carcinogenesis (7, 19, and 28 weeks) employing a well-established passage-matched HaCaT cell line model of arsenic-induced cSCC. Here, we performed longitudinal differential expression analysis (miRNA and mRNA) between the different time points (7 vs 19 weeks and 19 vs 28 weeks) within unexposed and exposed groups, coupled to expression pairing and pathway analyses to differentiate the relative effects of long-term passaging and chronic iAs exposure. Data showed that 66-105 miRNA [p < .05; log2(fold change) > I1I] and 2826-4079 mRNA [p < .001; log2(fold change) > I1I] molecules were differentially expressed depending on the longitudinal comparison. Several mRNA molecules differentially expressed as a function of time, independent of iAs exposure were being targeted by miRNA molecules which were also differentially expressed in a time-dependent manner. Distinct pathways were predicted to be modulated as a function of time or iAs exposure. Some pathways were also modulated both by time and exposure. Thus, the HaCaT model can distinguish between the effects of passaging and chronic iAs exposure individually and corroborate our previously published data on effects of iAs exposure compared with unexposed passage matched HaCaT cells. In addition, this work provides a template for cell line-based longitudinal chronic exposure studies to follow for optimal efficacy.


Glomus tumor of a female breast: a case report and review of the literature.
Glomus tumor is a benign, subcutaneous neoplasm which usually arises in areas that are rich in glomus bodies, most commonly the digital area, and usually appears as a painful nodule. Glomus tumor of the breast is extremely rare, and there has been only limited information reported in the literature to date. We herein present a case of a glomus tumor arising from the breast, showing a well-circumscribed, hypervascular, solid and hypoechoic tumor within the retromammary fat. The tumor was resected and the patient's pain was relieved immediately after the surgery. She remains well without any symptoms after a year. This report describes a unique case of this type of tumor.


Exercise-induced precordial ST-segment depression in prior inferior myocardial infarction with single-vessel disease; with special reference to its mechanisms and distinction from multi-vessel disease.
We investigated the mechanisms of exercise-induced precordial ST-segment depression on the electrocardiogram in prior inferior myocardial infarction with single-vessel disease and attempted to differentiate the ST-segment depression between single- and multi-vessel disease. Subjects included three groups: group Ia (n = 11), inferior myocardial infarction with single-vessel disease that showed no precordial ST-segment depression; group Ib (n = 7), inferior myocardial infarction with single-vessel disease accompanied by precordial ST-segment depression; and group II (n = 10), inferior myocardial infarction with multi-vessel disease. The subjects underwent 12-lead exercise electrocardiography, stress Tl-201 myocardial imaging and stress radionuclide ventriculography. Exercise-induced precordial ST-segment depression observed in group Ib was associated with large infarction and infarction extending into the inferoseptal wall of the left ventricle on myocardial image. On stress ventriculography, worsening of the septal wall motion was more frequently observed in group Ib than in group Ia. Coronary arteriography revealed a higher rate of rich collateral vessels to the infarcted zone in group Ib than in group Ia. When we compared the diagnostic ability for detecting multi-vessel disease in prior inferior myocardial infarction, although sensitivity was not different among three tests, both exercise electrocardiography and radionuclide ventriculography had poor specificity and predictive value compared to stress Tl-201 myocardial imaging. Thus we concluded that exercise-induced precordial ST-segment depression observed in prior inferior myocardial infarction with single-vessel disease should reflect a peri-infarctional ischemia located in the inferoseptal wall of the left ventricle, and that stress Tl-201 myocardial imaging is the most accurate method for diagnosing multi-vessel disease in prior inferior myocardial infarction.


[Rheumatoid arthritis and HLA system. A search for correlations between histocompatibility antigens and characteristic features of the disease].
Possible correlations between the HLA antigens A, B, C and DR and the clinical and biological features of rheumatoid arthritis were investigated in 74 patients with positive serology. The DR 4 antigen was present in 46 of these patients (62%), being apparently more frequent in those whose disease had begun before the age of 35 (p less than 0.05). DR 4 was also more common in pure rheumatoid arthritis than in forms associated with Gougerot-Sjogren's syndrome (p less than 0.05). No correlation could be found between the HLA phenotype and the other parameters studied, i.e. sex, corticosteroid therapy. Steinbrocker's radiological stages, plasma levels of rheumatoid factor and gammaglobulins and presence of antinuclear antibodies.


Prostaglandin production by human polymorphnuclear leucocytes during phagocytosis in vitro.
Human polymorphonuclear leukocytes were found to be able to synthetize and release substantial amounts of PGE2' when stimulated by a phagocytic stimulus such as zymosan particles coated with complement. Hydrocortisone, at a concentration of 10(-5) M, which proved to be effective in other biological systems, failed to inhibit phagocytosis and PG release.


Theoretical mechanisms for synthesis of carcinogen-induced embryonic proteins: X. Correlation of the induceability of hepatomas and alpha-fetoprotein gene activity.
We have observed a distinct difference in the alpha-fetoprotein production of Sprague-Dawley rats and Swiss white mice. When both animals are fed a 1% D/L-ethionine diet, only the rat responds with increased levels of hepatic alpha-fetoprotein synthesis as shown by radioimmunoassay studies. Also, hybridization studies, with a complementary deoxyribonucleic acid for alpha-fetoprotein messenger ribonucleic acid, proved negative for the mouse, even after forty days on the 1% D/L-ethionine diet. This evidence, combined with other information leads us to believe that the mouse has a genomic regulatory system that is resistant to carcinogenic change by certain chemicals. Furthermore it may eventually be proven that hepatic tissue that is competent to have certain embryonic genes activated may also be capable of becoming neoplastic.


Juvenile laryngeal papillomatosis with pulmonary parenchymal spread. Case report and review of the literature.
A 6.5-year-old boy developed laryngeal papillomas at 20 months of age and pulmonary parenchymal spread at age 3.5 years, the lung lesions beginning as solid nodules which rapidly cavitated. The cavitary lesions have stabilized in size but no appreciable improvement has resulted from trials of bleomycin, methotrexate, or interferon. A review of 14 other cases indicates that the lung lesions may develop many years after the onset of laryngeal papillomatosis, and the lung lesions do not tend to regress spontaneously as uncomplicated juvenile laryngeal papillomas often do. Three of 15 patients developed carcinomas in their lung lesions without prior therapeutic irradiation.


Completely self-contained cell culture system: from storage to use.
In vitro cell culture systems provide researchers the appropriate tools for effectively studying cell growth and differentiation, understanding cellular response to specific environmental stimuli, and elucidating the function of heterologous biological molecules produced from expression systems. All in vitro cell culture systems require a specific culture media formulated to the nutritional and metabolic requirements of the particular cell type to be cultured. However, the complexity of these systems varies depending on the model organism origin of the cells being cultured (e.g., bacteria, plants, yeast or animal). Unlike bacteria and yeast, mammalian cell cultures require sophisticated auxiliary technologies (e.g., controlled gas mixtures and pressure flow systems, specialized facilities and equipment) and careful handling by trained personnel. These complex requirements pose a limitation to transferring cells to and from remote field locations for investigations. Furthermore, this limitation is a technical hurdle in the development of technologies involving use of live cells (e.g., cytosensors). We identified a novel and unrealized feature in the conventional cell culture system that may be exploited to adapt simple existing technologies to form a portable apparatus for storing and growing cells. The approach we describe is a completely self-contained cell culture system that not only will bring down the cost of culturing cells but also will expand cell culture applications in medicine, research, environmental health, and safety.


Four amino acids of an insect densovirus capsid determine midgut tropism and virulence.
Densoviruses are insect parvoviruses that are orally infectious for Lepidoptera. To assess the mechanisms underlying their specificity and their virulence, we investigated the role of eight candidate residues in the densovirus capsid. We showed that the substitutions of four amino acids were associated with decreased virulence due to a decreased ability to cross the host midgut epithelium, without an effect on viral replication in other tissues.


Encephalocraniocutaneous lipomatosis.
Two patients with encephalocraniocutaneous lipomatosis have been studied. The main features of the syndrome are unilateral cutaneous and ophthalmologic lesions with ipsilateral cerebral malformations. Seizures beginning in infancy and varying degrees of mental retardation are present in affected patients. The involved tissues are derived from the embryonic ectodermal and mesodermal layers.


[Outcome of cervical carcinoma with locoregional lymph node involvement by FDG-PET].
To assess the outcome of cervical carcinoma with positive nodes on fluorodesoxyglucose positon emission tomography scans (FDG-PET). Patients with cervical carcinoma who had pelvic and/or para-aortic lymph nodes involvement by FDG-PET and treated with a curative intent from 2003 to 2007 were retrospectively studied. All patients received pelvic (and possibly para-aortic) radiotherapy with chemotherapy, followed by brachytherapy, and possibly surgery. The first site of relapse was classified as follows: local, nodal (pelvic or para-aortic) or metastatic. Forty patients were included the study. Median age was 47 years (range: 28-78). Thirty patients had nodal involvement limited to pelvic area and ten had a para-aortic involvement. Median follow-up was 42.5 months (range: 11-85). There were 22 relapses and 20 deaths: 20 due to relapse and one due to late toxicity. Three-year survival is 50 % (95 % confidence interval [CI]: 36-65). First relapse was: metastatic for 33 % (13/40), local for 20 % (8/40) and isolated nodal for 5 % (2/40). Multivariate analysis has revealed that only staging according to International Federation of Gynecology and Obstetrics (FIGO) and para-aortic involvement had a significant impact on survival. Three-year survival was 58 % (CI: 39-74) and 24 % (CI: 7-57) (P=0.009) in patient without and with para-aortic involvement, respectively. Para-aortic involvement by FDG-PET is a significant prognostic factor for overall survival. Local control at primary site remains of paramount importance for patient with nodal involvement. Isolated nodal failures are scarce.


Collagenase-solubilized lipoprotein--glycosaminoglycan complexes of human aortic fibrous plaque lesions.
The interaction of lipoproteins and arterial connective tissue macromolecules was studied using human atherosclerotic plaque tissues. After extraction with 0.15 M NaCl, the tissues were repeatedly digested with collagenase followed by elastase. The collagenase-solubilized lipoprotein--GAG complexes were isolated by gel-filtration and ultracentrifugation and analyzed for lipids, GAG and protein. While extraction by 0.15 M NaCl released only about 13% of the total cholesterol from the tissues, subsequent digestions by collagenase and elastase yielded 60% and 17% cholesterol, respectively. Both 0.15 M NaCl and collagenase treatment released equal amounts of GAG and accounted for 84% of the total GAG. Immunologically, lipoproteins resembled serum apoB-containing lipoproteins. Bio-Gel A-50m column chromatography of collagenase-extracted materials gave a single peak which contained lipoproteins of 1.006 and 1.063 floating densities, GAG and hydroxyproline. Hyaluronic acid (HA) and chondroitin 6-sulfate were identified; HA was the major GAG. Although the precise nature of the interaction of arterial connective tissue components with lipoproteins is not completely understood, isolation of such complexes indicates the importance of these macromolecules in sequestration of lipoproteins.


Multiscale Relaxation Behavior of Amorphous Plasticized Poly(vinyl butyral).
As a key component in laminated glass, plasticized polyvinyl butyral (PVB) interlayer is a kind of impact-resistant polymer material with high toughness. Recently, by using ultrasmall angle X-ray scattering (USAXS) technique, Stretch-induced phase-separated structure on the scale of hundreds of nanometers formed in plasticized PVB for the first time is reported. In this work, the multiscale relaxation behavior of plasticized PVB is further investigated. The relaxation behavior of deformed plasticized PVB is studied from macroscopic stress, mesoscopic phase-separated structure, and microscopic chain segment by combining USAXS, and birefringence with in situ stretching device. The contributions of chain segments and hydrogen bonding clusters for the multiscale relaxation behavior are discussed.


Inhibition of phospholipase C attenuates liver mitochondrial calcium overload following cold ischemia.
Graft failure due to cold ischemia (CI) injury remains a significant problem during liver transplantation. During CI, the consumption of ATP and the increase in cellular Ca concentration may result in mitochondrial Ca (mCa) overload through the mCa uniporter, which can ultimately lead to apoptosis and graft nonfunction. We recently identified phospholipase C-dl (PLC-dl) as a novel regulator of mCa uptake in the liver, and now extend those studies to examine the role of mitochondrial PLC in liver CI injury. Rat livers were perfused with University of Wisconsin (UW) solution. Half was homogenized immediately; the other half was cold-stored for 24 hr in UW. Mitochondria were extracted by differential centrifugation and incubated in buffer containing ATP and 0.1 or 0.2 microM Ca. The selective PLC inhibitor, U-73122, was added to determine the effects of PLC inhibition on mCa uptake following CI. Western blots and densitometry quantified mitochondrial PLC expression. Mito Tracker Red fluorescence microscopy was used to verify mitochondrial transmembrane potential. Twenty-four hour CI caused a significant increase in mCa uptake (P<0.001), and increasing extramitochondrial Ca potentiated this effect. The PLC inhibitor, U-73122, decreased mCa uptake in nonischemic mitochondria (P<0.001), and had a greater effect on CI mitochondria (P<0.001). Mitochondrial PLC-dl expression increased 175+/-75% following CI (P<0.05). These data demonstrate that PLC-dl is essential for mCa uptake following CI, and that the PLC pathway may be sensitized by CI. The CI-induced increase in mitochondrial PLC-delta1 expression represents a novel mechanism whereby mCa uptake can increase independently of cytosolic conditions.


Impact of anti-obesity medication initiation and duration on weight loss in a comprehensive weight loss programme.
This retrospective study aimed to evaluate the impact of anti-obesity medication (AOM) initiation, usage and duration on weight loss in a 72-week precision obesity programme. The type of AOM, diet and exercise plan was chosen based upon an individual's biological and psychosocial needs. The 72-week study duration allowed for a fair investigation of the downstream impact of delayed versus early AOM initiation. Participants, aged ≥18 years with body mass index ≥30 kg m-2, enrolled from 1 March 2015 to 1 April 2017, were included. Subgroups were assigned by AOM usage (users versus non-users, early [before 8 weeks] versus delayed [after 8 weeks] AOM initiation and short [<6 months] versus long [≥6 months] AOM duration). Primary endpoints included change in baseline weight at 72 weeks and proportions achieving ≥5%, ≥10% and ≥15% weight loss. Outcomes were compared between subgroups. Mean age and body mass index (N = 129) were 45.0 ± 14.0 years and 37.0 ± 6.0 kg m-2, respectively; 67% were female. At week 72, AOM users (N = 71) achieved significantly greater mean percentage reduction in baseline weight than non-users (N = 58). On average, baseline weight decreased by 14.04 ± 6.2% in users versus 10.9 ± 6.8% in non-users (P = 0.008); 84% and 94% of non-user and AOM users lost >5% weight loss (P = 0.006). A higher proportion of users lost ≥15% of weight (45.1% vs. 19.0%; P < 0.001). Mean percentage reduction in weight was greater for early versus delayed starters (-17.60 ± 5.3% vs. -13.95 ± 5.5%; P = 0.024), and longer AOM usage trended towards increased weight loss. Early initiation of AOM may enhance weight loss.


Novel degradable oligoethylenimine acrylate ester-based pseudodendrimers for in vitro and in vivo gene transfer.
A novel class of cationic hyperbranched polymers, containing branched oligoethylenimine (OEI 800 Da) as core, diacrylate esters as linkers and oligoamines as surface modification, was synthesized and evaluated regarding their structure-activity relationship as gene carriers. We show that pseudodendritic core characteristics as well as different surface modifications on the core influence DNA-binding ability, cytotoxicity and transfection efficiency. As most promising gene carrier, the pseudodendrimer HD O, that is, the OEI 800 Da core modified with hexane-1,6-diol diacrylate and surface-modified with OEI 800 Da, was identified. HD O exhibits efficient DNA-condensing ability to nanosized polyplexes (100-200 nm), low cytotoxicity, a degradation half-life of 3 days at 37 degrees C at physiological pH and in vitro reporter gene-expression levels similar to high molecular weight linear and branched polyethylenimines (PEIs) (LPEI and BPEI). In vivo studies in mice reveal that HD O/DNA polyplexes upon i.v. tail-vein injection have the potential for transfection of tumor tissue at levels comparable to that obtained with LPEI. Importantly, HD O was better tolerated than LPEI, while transgene expression was more tumor-specific and much lower in all other investigated organs, especially in the lung (15,000-fold lower compared with LPEI).


"Handing out non-prescribed antibiotics is storing up trouble for the next generation!" Unpacking multistakeholder views of drivers and potential solutions in Ethiopia.
Antibiotic resistance is a global health crisis, with inappropriate antibiotic use often being linked to non-prescribed antibiotic dispensing practices. This study aimed to examine the perspectives of multiple stakeholders on the drivers and potential solutions for non-prescribed antibiotic dispensing in Ethiopian community drug retail outlets (CDROs). Despite the prescription only use policies, the practice remains prevalent in Ethiopia. Many factors are thought to contribute to this issue, although little research is available for non-urban settings. A phenomenological qualitative study was conducted. Pharmacy professionals (owners or employees) working in non-urban towns CDROs were selected through a simulated client study, which identified CDROs that had dispensed antibiotics without a prescription. Some high-level decision makers in the Ethiopian health system were also purposively selected. Interviews were conducted in-person and over the phone or via Zoom. The interview data were transcribed verbatim, translated to English, and thematically analysed. NVivo 12 software was used to assist with coding. CDRO pharmacy professionals (n = 18) and five decision makers were interviewed. Most professionals (61%) were pharmacists working in drug stores, with one to 11 years of work experience. Several contributing factors were identified at the level of patients, CDRO staff, and the healthcare system. These included economic interests, inadequate knowledge and inappropriate attitudes about antibiotic use or supply, and issues within the healthcare system included inaccessibility and insufficient capacity, absence of or a weak enforcement of prescription-only regulations or service supervision. Additionally, patient-related factors included a lack of knowledge and inappropriate attitudes about antibiotics use and their supply, previous successful treatment experience and a culture of seeking out antibiotics. A complex set of modifiable factors related to patients, CDRO staff and healthcare system were identified that contribute to the non-prescribed supply of antibiotics. Due to this complexity, a single solution will not resolve the issues. Therefore, a range of multifaceted solutions have been suggested, including stricter regulation, increasing availability and accessibility of healthcare services, collaboration, and local consensus-building among CDROs, regular training for CDRO staff, and using community social events to educate the public about responsible use of antibiotics.


Role of proteasomal activity in the induction of acrosomal exocytosis in human spermatozoa.
Sperm-associated proteasomes have been suggested to play an important role during fertilization in animals. To delineate the role of these proteasomes during fertilization in humans, the present study reports proteasomal proteolytic activity both in noncapacitated and capacitated human spermatozoa, which is not altered in the presence of baculovirus-expressed recombinant human zona pellucida glycoprotein-3 (ZP3) and zona pellucida glycoprotein-4 (ZP4). However, inhibition of proteasomal proteolytic activity by clasto-lactacystin beta-lactone (CLBL) and Z-Leu-Leu-Leu-CHO (MG132), which are specific inhibitors of the 20S proteasomal core proteases, led to a significant (P < 0.05) inhibition of induction of acrosome reaction mediated by both recombinant human ZP3 and ZP4. Both inhibitors, however, failed to inhibit the induction of acrosomal exocytosis mediated by pharmacological agonist, calcium ionophore (A23187). The binding of recombinant human ZP3 and ZP4, labelled with fluorescein isothiocyanate, to the capacitated spermatozoa was not affected in the presence of proteasomal inhibitors. These observations suggest a role of the sperm proteasome in the induction of ZP3- and ZP4-mediated acrosomal exocytosis upstream of calcium signalling in humans.


A mutational analysis of the active site of human type II inosine 5'-monophosphate dehydrogenase.
The oxidation of IMP to XMP is the rate-limiting step in the de novo synthesis of guanine ribonucleotides. This NAD-dependent reaction is catalyzed by the enzyme inosine monophosphate dehydrogenase (IMPDH). Based upon the recent structural determination of IMPDH complexed to oxidized IMP (XMP*) and the potent uncompetitive inhibitor mycophenolic acid (MPA), we have selected active site residues and prepared mutants of human type II IMPDH. The catalytic parameters of these mutants were determined. Mutations G326A, D364A, and the active site nucleophile C331A all abolish enzyme activity to less than 0.1% of wild type. These residues line the IMP binding pocket and are necessary for correct positioning of the substrate, Asp364 serving to anchor the ribose ring of the nucleotide. In the MPA/NAD binding site, significant loss of activity was seen by mutation of any residue of the triad Arg322, Asn303, Asp274 which form a hydrogen bonding network lining one side of this pocket. From a model of NAD bound to the active site consistent with the mutational data, we propose that these resides are important in binding the ribose ring of the nicotinamide substrate. Additionally, mutations in the pair Thr333, Gln441, which lies close to the xanthine ring, cause a significant drop in the catalytic activity of IMPDH. It is proposed that these residues serve to deliver the catalytic water molecule required for hydrolysis of the cysteine-bound XMP* intermediate formed after oxidation by NAD.


The asymptotic equipartition property in reinforcement learning and its relation to return maximization.
We discuss an important property called the asymptotic equipartition property on empirical sequences in reinforcement learning. This states that the typical set of empirical sequences has probability nearly one, that all elements in the typical set are nearly equi-probable, and that the number of elements in the typical set is an exponential function of the sum of conditional entropies if the number of time steps is sufficiently large. The sum is referred to as stochastic complexity. Using the property we elucidate the fact that the return maximization depends on two factors, the stochastic complexity and a quantity depending on the parameters of environment. Here, the return maximization means that the best sequences in terms of expected return have probability one. We also examine the sensitivity of stochastic complexity, which is a qualitative guide in tuning the parameters of action-selection strategy, and show a sufficient condition for return maximization in probability.


Spotlight on Ki67 as a prognostic marker in early breast cancer: all that glitters may not be gold.
Kang and colleagues evaluated on a case series of 1848 breast cancer (BC) patients operated for a first primary ER positive HER2 negative BC if Ki67 expression is a significant prognostic factor only when PgR expression is low. The authors concluded that Ki67 with 10% cut off value is a prognostic factor only under low PgR expression level in early BC. We would like to underline, that as already stated in our previous papers, we believe that proliferation is important to define the decision-making of adjuvant therapies in early BC. The issue on Ki67 detection is the poor reproducibility due to different antibody clones, platforms and scoring methods. Not less important is that different Ki67 cut off values have been used by San Gallen guidelines and changed overtime. Then, despite the interesting results, we believe it would be better to use Ki67 biomarker in according to the standard Ki67 cut off according to San Gallen guidelines. Nowadays, standardization and optimization of Ki67 is still an urgent need.


Feasibility of Behavioral Weight Loss Treatment Enhanced with Peer Support and Mobile Health Technology for Individuals with Serious Mental Illness.
Effective and scalable lifestyle interventions are needed to address high rates of obesity in people with serious mental illness (SMI). This pilot study evaluated the feasibility of a behavioral weight loss intervention enhanced with peer support and mobile health (mHealth) technology for obese individuals with SMI. The Diabetes Prevention Program Group Lifestyle Balance intervention enhanced with peer support and mHealth technology was implemented in a community mental health setting. Thirteen obese individuals with SMI participated in a pre-post pilot study of the 24-week intervention. Feasibility was assessed by program attendance, and participant satisfaction and suggestions for improving the model. Descriptive changes in weight and fitness were also explored. Overall attendance amounted to approximately half (56 %) of weekly sessions. At 6-month follow-up, 45 % of participants had lost weight, and 45 % showed improved fitness by increasing their walking distance. Participants suggested a number of modifications to increase the relevance of the intervention for people with SMI, including less didactic instruction and more active learning, a simplified dietary component, more in depth technology training, and greater attention to mental health. The principles of standard behavioral weight loss treatment provide a useful starting point for promoting weight loss in people with SMI. However, adaptions to standard weight loss curricula are needed to enhance engagement, participation, and outcomes to respond to the unique challenges of individuals with SMI.


Optokinetic nystagmus in homonymous hemianopia due to a strictly occipital lesion.
Optokinetic nystagmus (OKN) was tested in 15 patients with unilateral strictly occipital brain lesions and complete homonymous hemianopia and compared with findings in a group of normal controls. Quantitative analysis of the results in the patients revealed a bilateral disorder of OKN. When the stimulus was moved in the direction opposite to the hemianopic field, there was a significant decrease in optokinetic gain, and the amplitude of nystagmus decreased. There was no correlation between OKN and size of the residual macular field.


[The content of thromboxane B2 and 6-ketoprostaglandin F1 alpha of the blood plasma in patients with psoriasis and children with allergic dermatoses].
The blood plasma levels of a number of endogenous prostaglandins have been measured by column chromatography followed by radioimmunoassay in 33 patients with psoriasis and in 22 children with allergic dermatoses. The findings evidence an increase of these prostanoids at the peak of the skin process exacerbation, thus indicating their role in the pathogenesis of psoriasis and allergic dermatoses in children.


Disruption of Phaffia rhodozyma cells and preparation of microencapsulated astaxanthin with high water solubility.
A novel process was developed for encapsulation of astaxanthin from Phaffia rhodozyma. The yeast cells were disrupted by glass beads and the high shearing force partially emulsified the astaxanthin in aqueous phase. The enzymolysis method was then adopted to prepare the yeast extract for a full use of the cells. The gelatin and porous starch were used to microencapsulate the emulsified astaxanthin. Under optimized conditions, the recovery of amino nitrogen and solid reached 3.68 ± 0.32% and 49.22 ± 2.34%, respectively. The microencapsulation conditions were optimized through orthogonal experiment and the encapsulation efficiency, loading astaxanthin, and amino-nitrogen reached 88.56%, 1.55 mg/g, and 1.35 ± 0.14%, respectively. The water solubility of microcapsules reached 81.5 ± 0.35%. Color and storage stability analysis showed that microencapsulation of astaxanthin possessed higher thermal stability. The results demonstrated that the established process was effective and practical.


Exploring health seeking behaviors for common cold management.
The prevalence of common cold can impose financial burden on the healthcare systems, despite its simple and self-limiting symptoms. This study examines the behavior of patients suffering from symptoms of the common cold and explores the factors that may influence such behaviors. A descriptive-analytic cross-sectional study was conducted in 2019, in Tehran, Iran, using cluster sampling in socioeconomically diverse areas within the city. The participants' behaviors and related factors were evaluated using a 10-item questionnaire. Data collection process involved selecting 5 shopping centers and 404 individuals participated the study. SPSS version 24 was used for analysis. The results showed that 42.1% of the respondents would consult a physician immediately upon experiencing cold symptoms, while 11.4% would consult a pharmacist.In addition, 14.3% would try self-medication, 28.3% relied on traditional home remedies, and 15%indicated not to make use of any remedies or interventions. The study indicated a correlation between people's behaviors concerning the common cold and their level of health self-confidence, knowledge of the common cold, lifestyle, gender, marital status, occupational status, insurance status, and average family spending. The findings of this study are significant in that they shed light on the behaviors of individuals and associated factors related to seeking medical assistance for the common cold. This knowledge can assist healthcare systems in developing strategies aimed at enhancing treatment outcomes, and decreasing costs.


The impact of Hounsfield unit-related variables on percutaneous nephrolithotomy outcomes.
We aimed to identify the association between Hounsfield Unit(HU)-related variables and percutaneous nephrolithotomy (PCNL) outcomes. We enrolled patients with single renal stones (1-3 cm) who underwent single-tract PCNL between January 2014 and October 2019. Demographics and stone characteristics were retrospectively reviewed. Preoperative computerized tomography (CT) and follow-up CT within at least 3 months after PCNL were included in this analysis. Stone-free status was defined as residual stone measuring ≤ 2 mm within 3 months postoperatively. HU and cross-sectional area (CSA) were measured using the free-draw technique. We analyzed HU-related variables using logistic regression model for outcomes. Altogether, 188 out of 683 patients met the inclusion criteria. The stone-free rate (SFR) was 79.2%. There were no significant differences in age, sex, BMI, ASA class, laterality, pre-op shockwave lithotripsy, stone size, stone burden, skin-to-stone distance, and HU between the stone-free and remnant groups. CSA and HU/CSA in the stone-free and remnant groups were 94.5 ± 46.1 and 128.3 ± 98.5 (p = 0.043) and 10.1 ± 5.6 and 7.3 ± 3.4 (p = 0.001), respectively. Multivariate logistic regression analysis revealed that pelvis, ureteropelvic junction stones, and HU/CSA were independent predictors of SFR. HU did not affect PCNL outcomes. We believe that HU/CSA could be used for determining stone treatment plans and predicting outcomes.


Emphysematous cholecystitis presenting as gas-forming liver abscess and pneumoperitoneum in a dialysis patient: a case report and review of the literature.
Emphysematous cholecystitis is a rare variant of acute cholecystitis with a high mortality rate. The combination of emphysematous cholecystitis, liver abscess and pneumoperitoneum are even rarer. Herein we present a case of emphysematous cholecystitis in a senile diabetic lady who had worsening hemodynamics while undergoing hemodialysis. A 64-year-old woman with history of type 2 diabetes mellitus and end stage renal disease with regular hemodialysis presented to the emergency department with a 1-day history of sudden onset of lassitude and hypotension during hemodialysis. The result of a computed tomography (CT)-scan revealed air encircling the gallbladder, liver parenchymal and minimal pneumoperitoneal and liver abscess with no cholelithiasis. The patient had received empirical antibiotics with piperacillin-tazobactam 2.25 g intravenous route every 6 h for 14 days and cholecystectomy with surgical debridement and lead an uneventful postoperative hospital course. Escherichia coli was demonstrated as well as blood culture and peritoneal fluid culture. In a senile diabetic and dialysis patient, we should take emphysematous cholecystitis into consideration once vague abdominal pain occurrs. Empirical antibiotic therapy and adequate surgical intervention should take place as soon as possible.


Synthesis and degradation of polyphosphate in the fission yeast Schizosaccharomyces pombe: mutations in phosphatase genes do not affect polyphosphate metabolism.
The fission yeast Schizosaccharomyces pombe was found to accumulate large amounts of polyphosphate, particularly when grown on arginine as the nitrogen source. Upon transfer to a medium without phosphate, polyphosphate was degraded and served as an endogenous phosphate reserve. When phosphate was added again after a prolonged period of phosphate starvation, fission yeast cells synthesized more polyphosphate than they had contained before starvation, a phenomenon known as over-compensation. Strains carrying mutated structural genes for three different phosphatases, pho1, pho2 or pho3, degraded polyphosphate at the same rate as the wild-type strain during phosphate starvation and showed the same type of over-compensation when phosphate was added again.


A Chiral-Nanoassemblies-Enabled Strategy for Simultaneously Profiling Surface Glycoprotein and MicroRNA in Living Cells.
Assemblies of nanomaterials for biological applications in living cells have attracted much attention. Herein, graphene oxide (GO)-gold nanoparticle (Au NP) assemblies are driven by a splint DNA strand, which is designed with two regions at both ends that are complementary with the DNA sequence anchored on the surface of the GO and the Au NPs. In the presence of microRNA (miR)-21 and epithelial cell-adhesion molecule (EpCAM), the hybridization of miR-21 with a molecular probe leads to the separation of 6-fluorescein-phosphoramidite-modified Au NPs from GO, resulting in a decrease in the Raman signal, while EpCAM recognition reduces circular dichroism (CD) signals. The CD signals reverse from negative in original assemblies into positive when reacted with cells, which correlates with two enantiomer geometries. The EpCAM detection has a good linear range of 8.47-74.78 pg mL-1 and a limit of detection (LOD) of 3.63 pg mL-1 , whereas miR-21 detection displays an outstanding linear range of 0.07-13.68 amol ng-1RNA and LOD of 0.03 amol ng-1RNA . All the results are in good agreement with those of the Raman and confocal bioimaging. The strategy opens up an avenue to allow the highly accurate and reliable diagnosis (dual targets) of clinic diseases.


Evaluation of MRI issues for a new neurological implant, the Sensor Reservoir.
A new neurological implant, the Sensor-Reservoir, was developed to provide a relative measurement of ICP, which permits a noninvasive technique to detect and localize occlusions in ventricular drainage systems and, thus, to identify mechanical damage to shunt valves. The "reservoir" of this device can be used to administer medication or a contrast agent, to extract cerebral spinal fluid (CSF), and with the possibility of directly measuring ICP. The Sensor-Reservoir was evaluated to identify possible MRI-related issues at 1.5-T/64-MHz and 3-T/128-MHz. Standard testing techniques were utilized to evaluate magnetic field interactions (i.e., translational attraction and torque), MRI-related heating, and artifacts at 3-T for the Sensor-Reservoir. In addition, 12 samples of the Sensor-Reservoir underwent testing to determine if the function of these devices was affected by exposures to various MRI conditions at 1.5-T/64-MHz and 3-T/128-MHz. Magnetic field interactions for the Sensor-Reservoir were not substantial. The heating results indicated a highest temperature rise of 1.8 °C, which poses no patient risks. Artifacts were relatively small in relation to the size and shape of the Sensor-Reservoir, but may interfere diagnostically if the area of interest is near the device. All devices were unaffected by exposures to MRI conditions at 1.5-T/64-MHz and 3-T/128-MHz. When specific guidelines are followed, the Sensor-Reservoir is "MR conditional" for patients undergoing MRI examinations at 3-T or less.