Biologically inspired stealth - Camouflaged strategies in nanotechnology for the improved therapies in various diseases.
Nanotechnology has received increasing attention in the past decade and it's being used as a model for developing better treatments for a variety of diseases. Despite the fact that nanotechnology-based therapy has greatly improved treatment regimens, it still faces challenges such as inadequate circulation, insufficient accumulation at the target region, and undesired toxicity. In this regard, scientists are working on producing cell-membrane camouflaged nanoparticles as a biomimetic technique for modifying the surface of existing nanoparticles to produce significant therapeutic benefits following imparting myriad of desired functionalities. Membranes originating from erythrocytes, white blood cells, cancer cells, stem cells, platelets, or bacterial cells have been used to coat nanoparticle surfaces and create biologically inspired camouflaged nanoparticles. These biomemitic delivery systems have been proven to have potential applications in diagnosing and treating vaiorus diseases, including drug administration, immunisation, immunological regulation, and detoxification. From its inception to the present, we provide a complete description of this advanced technique for functionalizing nanoparticle surfaces. The method of making these membrane coated nanoparticles as well as their characterisation have been thoroughly discussed. Following that, we focused on the diversity of cell membranes derived from distinct cells in the evolution of nanoparticles, emphasising how these biologically inspired stealth - camouflaged techniques have led to increased therapeutic efficacy in a variety of disease states.


Claymation art therapy in early phase psychosis: A qualitative study to explore participants' experiences with the program and identify outcome effects.
Art therapy is a complex intervention that has mixed evidence for people with schizophrenia and scant research in early phase psychosis. Benefits appear to depend on level of engagement and more qualitative studies are needed to elucidate how it works and what outcomes to measure. The purpose of this study was to determine the feasibility of a 13-week Claymation art therapy group intervention for young adults with early phase psychosis, and to explore participants' experiences with the program and to identify outcome effects. Thirteen participants completed the intervention in two cohorts. The participants' experiences were explored through qualitative thematic analysis of individual interviews postintervention and at 3-month follow-up. The program had a 62% retention rate and an 80% attendance rate. Qualitative analysis of postintervention and 3-month follow-up interviews identified six themes that described program elements: (a) Claymation valued; (b) film screening fostered support; (c) getting to know each other through art; (d) connecting with others with lived experience; (e) opportunity to build skills; and (f) supportive facilitators. Five themes were identified as outcome effects from both time points: (a) stress relief; (b) self-discovery; (c) pride in art; (d) confidence and hope; and (e) engagement in meaningful activity postintervention. Two themes were unique to the 3-month follow-up interviews: (a) Claymation was enabling and (b) showing my film. This group Claymation art therapy intervention effectively engaged people with early phase psychosis and the qualitative analysis identified program elements and outcome effects that can be evaluated in future studies.


Treatment of hepatitis C in hemophiliacs.
Hepatitis C virus (HCV) infection is a major cause of morbidity and mortality in hemophiliacs who received nonvirucidally treated large-pool clotting factor concentrates before 1986. In fact, although many hemophiliacs infected with HCV have a slow progression of liver disease, in a minority of them hepatitis evolves toward end-stage liver disease and hepatocarcinoma. Moreover, a significant percentage of HCV-infected hemophiliacs were also coinfected with human immunodeficiency virus (HIV), which can accelerate the progression of liver disease. Thus, the aim of anti-HCV therapy is to interrupt the chronic infection in order to prevent the progression of hepatitis to cirrhosis, liver decompensation, cancer and, ultimately, death. In this review we present the literature data on anti-HCV treatment in hemophiliacs. Combination therapy with interferon (IFN) and ribavirin has improved the poor results obtained with IFN monotherapy and has become the standard treatment of chronic hepatitis C. Given the positive results obtained with pegylated interferon plus ribavirin in nonhemophiliacs, ongoing trials are evaluating this promising therapy in HCV-chronically infected hemophilic patients; preliminary results show a sustained response rate similar to that in patients without coagulopathy. Finally, based on the encouraging results in coinfected nonhemophiliacs, anti-HCV treatment should also be considered for those HIV-positive hemophiliacs in whom anti-retroviral treatment has stabilized the HIV infection.


Adaptation of AmtR-controlled gene expression by modulation of AmtR binding activity in Corynebacterium glutamicum.
In corynebacteria, nitrogen regulation is controlled by the TetR family protein AmtR, which was extensively studied in the last years. In frame of these studies a number of AmtR binding sites were identified and characterized and it became obvious that for distinct genes the number and sequences of these sites varied significantly. In this study, the influence of numbers and alterations of AmtR binding sites were addressed by in vivo and in vitro studies. It can be concluded that in general a single highly conserved AmtR site is sufficient for stringent regulation and that non-conserved binding sites have a very limited influence, despite the fact that binding of AmtR was shown for several of these sites, e.g. upstream of amtA, amtB and gdh. Furthermore, the reason for and consequences of the lack of AmtR autoregulation were addressed in vivo. The introduction of a spacing nucleotide between the two conserved half sites of the AmtR binding box alone is sufficient to restore AmtR autoregulation. The main differences observed between wild type and an AmtR autoregulation strain were a slightly enhanced background of transcription of AmtR-controlled genes and a slightly slower response to nitrogen limitation.


IgH class switch recombination to IgG1 in DNA-PKcs-deficient B cells.
To assess the role of the DNA-PKcs nonhomologous DNA end-joining (NHEJ) protein in Ig heavy chain class switch recombination (CSR), we assayed CSR ability of DNA-PKcs-deficient (DP-T) B cells generated via complementation of DP-T mice with Ig heavy chain and light chain knock-in transgenes (DP-T/HC/LC mice). DP-T/HC/LC mice were severely deficient for all serum IgH isotypes except IgM and, unexpectedly, IgG1. Upon appropriate stimulation, DP-T/HC/LC B cells showed normal proliferation, germline C(H) gene transcription, and AID induction, indicating that DNA-PKcs deficiency did not affect cellular events upstream to CSR. Yet, in vitro activated DP-T/HC/LC B cells again underwent switching only to IgG1 and, like wild-type cells, frequently underwent CSR to gamma1 on both chromosomes. We conclude that DNA-PKcs is required for CSR to most C(H) genes but that CSR to gamma1 occurs via a DNA-PKcs-independent mechanism.


A distinctive colour associated with high iodine content in malignant pleural effusion from metastatic papillary thyroid cancer: a case report.
Pleural effusions are a common clinical problem and affect about one million people in the United States and United Kingdom each year. Over 60 causes of pleural effusion have been identified; establishing the definitive aetiology can be difficult, and often requires invasive procedures. Guidelines state that macroscopic examination of the fluid should be the first step in determining the aetiology of a pleural effusion. Papillary thyroid carcinoma is an uncommon cause of malignant pleural effusion, with only 10 cases reported in the literature, their physical characteristics and composition having been rarely described. We describe for the first time a distinctive brown colour of the malignant effusion (despite centrifugation) from a rare case of metastatic papillary thyroid cancer to the pleura, associated with a high pleural fluid iodine content. Such a characteristic may be useful in expediting diagnosis of a malignant pleural effusion in the appropriate clinical context. We present the case of a 71-year-old Caucasian man with metastatic papillary thyroid cancer; a large, long-standing, right-sided pleural effusion and a 83-fold higher pleural thyroglobulin level compared to corresponding serum, supporting this malignancy as the cause of the patient's effusion. The pleural fluid had a distinctive pigmentation similar to iodine-containing antiseptic preparations. Biopsy during medical thoracoscopy confirmed metastatic papillary thyroid carcinoma. Analysis of pleural fluid showed a pleural thyroglobulin level over 80 times that of serum levels (29,000μg/L versus 350ug/L). Pleural fluid iodine content was 23,000ug/L and may account for the fluid's distinctive pigment, as iodine is an essential component in thyroglobulin and thyroid hormone synthesis. Pleural fluid pigmentation may aid diagnosis in the appropriate clinical setting. A distinctive iodine-like brown colour of pleural fluid may represent elevated iodine content and should raise consideration of metastatic thyroid cancer as a cause for a pleural effusion.


Five-year changes in population blood pressure and hypertension prevalence. Results from the MONICA Augsburg surveys 1984/85 and 1989/90.
Two cardiovascular risk factor surveys were carried out in 1984/85 and 1989/90 in the Augsburg study region of the international World Health Organization (WHO) Monitoring Trends and Determinants of Cardiovascular Disease (MONICA) project. Independent random samples of the 25- to 64-year-old population were examined at each survey. Five-year changes in blood pressure (BP) and hypertension parameters were monitored in a population not targeted by any formal intervention program. Response rates in both surveys ranged close to 80%. Evaluation of selected quality indicators confirmed comparability of the two surveys in terms of BP measurement quality. Small but consistent decreases in mean systolic and diastolic BP were observed, particularly for women 35 years and older, whereas BP changes in men were less pronounced and inconsistent. Likewise, downward shifts of the 10th, 50th, and 90th percentiles of systolic and diastolic BP occurred in women and their slopes of BP rise with age decreased while such changes were less clear in men. The age-standardized prevalence of men and women with hypertensive BP (HBP; > or = 160/95 mm Hg) decreased slightly. This contrasted with rises in the prevalence of actual hypertension (those with HBP plus those taking antihypertensive drugs) for 45- to 64-year-old men, which originated from changes in hypertension management involving a more frequent drug treatment of borderline-hypertensive men (140 to 159/90 to 94 mm Hg) in 1989/90. There were notable overall increases in the awareness, treatment, and control of men and women with hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)


Irregularities of Coagulation in Hypertension.
This review article summarizes the role of coagulation in the pathogenesis of hypertension. It specifically focuses on significant factors and markers associated with coagulation, including D-dimer, fibrinogen and fibrin, prothrombin, P-selectin, soluble urokinase plasminogen activator receptor, thrombomodulin, tissue factor, tissue plasminogen activator, von Willebrand factor, β-thromboglobulin, and Stuart-Prower factor. D-dimer levels were elevated in hypertensive individuals compared to healthy controls, and the levels increased with the severity of hypertension. These findings indicate that increased coagulation activity of fibrin plays a role in the development of thromboembolic complications in hypertensive patients. Additionally, both fibrinogen levels and D-dimer levels displayed a positive correlation with the duration of hypertension, suggesting that these biomarkers were positively associated with the length of time an individual had been hypertensive. Increased systolic and diastolic blood pressures have been linked to higher levels of prothrombin time and activated partial thromboplastin time in individuals with hypertension as well as those with normal blood pressure. Also, the presence of P-selectin, produced by activated platelets and endothelial cells during angiotensin II stimulation, played a role in the development of cardiac inflammation and fibrosis associated with hypertension. Moreover, the change in systolic blood pressure was associated with baseline soluble urokinase plasminogen activator receptor (suPAR) in hypertensive participants, and the change in suPAR levels was associated with the development of hypertension. Moreover, it was observed a decrease in thrombomodulin expression in the placenta of preeclamptic patients, suggesting its potential involvement in placental dysfunction, possibly driven by an imbalance in angiogenic factors. Tissue factors and autophagy might have significant implications in the pathogenesis of chronic thromboembolic pulmonary hypertension, particularly in the context of vascular remodelling. Likewise, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) might be a promising biomarker for the early detection of pulmonary arterial hypertension and the von Willebrand factor is a candidate prognostic biomarker. The arterial β-thromboglobulin levels were significantly lower than venous levels. This article concludes that D-dimer, fibrinogen and fibrin, prothrombin, P-selectin, soluble urokinase plasminogen activator receptor, thrombomodulin, tissue factor, tissue plasminogen activator, von Willebrand factor, and β-thromboglobulin are important factors involved in the pathogenesis of hypertension.


The fate of intratracheal 14C-guanidinated pancreatic elastase in hamster lung.
Native pancreatic elastase and guanidinated elastase have similar in vitro and in vivo properties and produce emphysema of similar severity in hamsters. 14C-guanidinated pancreatic elastase (16,000 cpm/0.2 mg) was instilled into the trachea of anesthetized hamsters. Within 24 hours the radiolabel found in the lungs rapidly decreases to 12% of the original 16,000 cpm and to 1% after 96 hours. Most of the radiolabel and elastase activity found in the lungs can be removed by bronchopulmonary lavage up to 48 hours after installation. Although seemingly very small, there is a significant amount of radiolabel (1-2%) which cannot be removed from the lungs by extensive bronchopulmonary lavage.


GTP effects in rat brain slices support the non-interconvertability of M1 and M2 muscarinic acetylcholine receptors.
GTP (guanosine-5'-triphosphate) markedly reduced high-affinity 3H-oxotremorine-M binding to M2 receptors on brain slices in autoradiographic experiments while 3H-pirenzepine binding to M1 receptors was largely unaffected. The distribution of M1 receptors so labelled was also not altered by GTP to include former M2-rich regions, thus indicating that GTP could not, by itself, interconvert high agonist-affinity M2 receptors to M1 receptors.


It's not about pager replacement: an in-depth look at the interprofessional nature of communication in healthcare.
Institutions have tried to replace the use of numeric pagers for clinical communication by implementing health information technology (HIT) solutions. However, failing to account for the sociotechnical aspects of HIT or the interplay of technology with existing clinical workflow, culture, and social interactions may create other unintended consequences. To evaluate a Web-based messaging system that allows asynchronous communication between health providers and identify the unintended consequences associated with implementing such technology. Intervention-a Web-based messaging system at the University Health Network to replace numeric paging practices in May 2010. The system facilitated clinical communication on the medical wards for coordinating patient care. Study design-pre-post mixed methods utilizing both quantitative and qualitative measures. Five residents, 8 nurses, 2 pharmacists, and 2 social workers were interviewed. Pre-post interruption-15 residents from 5 clinical teams in both periods. The study compared the type of messages sent to physicians before and after implementation of the Web-based messaging system; a constant comparative analysis of semistructured interviews was used to generate key themes related to unintended consequences. Interruptions increased 233%, from 3 pages received per resident per day pre-implementation to 10 messages received per resident per day post-implementation. Key themes relating to unintended consequences that emerged from the interviews included increase in interruptions, accountability, and tactics to improve personal productivity. Meaningful improvements in clinical communication can occur but require more than just replacing pagers. Introducing HIT without addressing the sociotechnical aspects of HIT that underlie clinical communication can lead to unintended consequences.


Latinos and chronic hepatitis C: a singular population.
Latinos are the largest minority in the USA and have higher rates of HCV infection. The course of chronic hepatitis C in Latinos is more aggressive, with higher risk to develop cirrhosis than any other ethnic group or race. Available information suggests that more rapid progression of liver disease is aggravated by decreased efficacy to treatment with available therapies. The causes for more aggressive progression and decreased efficacy of treatment are complex. Factors related to metabolic syndrome, insulin resistance, and hepatic steatosis are important, as well as genetic differences, not only for metabolic syndrome but for immune responses to interferon. In addition, there are substantial barriers for Latinos to access medical care. Language, cultural differences, and socioeconomic factors, including lack of medical insurance, more frequent use of alcohol, and possible medical care provider bias, are significant obstacles to diagnosis and treatment. The severity of the liver disease and the association to metabolic syndrome medical conditions justify that Latinos be considered a special population with urgent need of intervention strategies. In this article we present all the available evidence on epidemiology, natural history of chronic hepatitis C, and efficacy of anti-HCV therapy in Latinos infected with HCV.


Pediatric hemofiltration: Normocarb dialysate solution with citrate anticoagulation.
Fourteen children, newborn to 17 years of age, underwent continuous veno-venous hemofiltration with dialysis (CVVHD), using a new FDA-approved bicarbonate-based calcium-free dialysis solution (Normocarb) in combination with citrate anticoagulation. Dialysis prescription included use of the PRISMA system (Gambro, Lakewood, Colo., USA), with ACD-A (Baxter, Deerfield, Ill., USA) for anticoagulation and Normocarb (Dialysis Solution, Richmond Hills, Ontario, Canada) for dialysate. Diagnosis included 11 children with sepsis and 3 children with tumor lysis syndrome. Mean weight was 31.6+/-4.7 kg (range 3.7-62 kg) and average length of therapy was 11.4+/-3.7 days (range 6 h to 67 days). Length of circuit patency was 71.3+/-7.2 h (range 6 h to 127 h), which was influenced in part by a decision to change circuits at 72 h as per manufacturer's recommendation. No bleeding occurred. This protocol utilizes industry-manufactured CVVHD machinery with both thermic and ultrafiltration control, with an effective anticoagulation protocol, and industry-produced bicarbonate dialysate. The use of industry machinery and solutions allows for consistent industrial quality assurance standards. This potentially may decrease the cost of therapy and minimize the risk of pharmacy errors that can occur with pharmacy-made dialysis solutions.


Fibroblasts express OvHV-2 capsid protein in vasculitis lesions of American bison (Bison bison) with experimental sheep-associated malignant catarrhal fever.
American bison (Bison bison) are particularly susceptible to developing fatal sheep-associated malignant catarrhal fever (SA-MCF) caused by ovine herpesvirus-2 (OvHV-2), a γ-herpesvirus in the Macavirus genus. This generally fatal disease is characterized by lymphoproliferation, vasculitis, and mucosal ulceration in American bison, domestic cattle (Bos taurus), and other clinically susceptible species which are considered non-adapted, dead-end hosts. The pathogenesis and cellular tropism of OvHV-2 infection have not been fully defined. An earlier study detected OvHV-2 open reading frame 25 (ORF25) transcripts encoding the viral major capsid protein in tissues of bison with SA-MCF, and levels of viral transcript expression positively correlated with lesion severity. To further define the cellular tropism and replication of OvHV-2 infection in vascular lesions of bison, immunofluorescence studies were performed to identify cell type(s) expressing ORF25 protein within tissues. Cytoplasmic and not nuclear ORF25 protein was demonstrated in predominantly perivascular fibroblasts in six bison with experimentally-induced SA-MCF, and there was no evidence of immunoreactivity in vascular endothelium, smooth muscle, or infiltrating leukocytes. The cytoplasmic distribution of viral major capsid protein suggests that viral replication in perivascular fibroblasts may be abortive in this dead-end host. These findings provide a novel foundation for defining the pathogenesis of vasculitis in non-adapted hosts with SA-MCF.


Culture temperature modulates aggregation of recombinant antibody in cho cells.
During production of therapeutic monoclonal antibodies (mAb), it is highly desirable to remove and control antibody aggregates in the manufacturing process to minimize the potential risk of immunogenicity to patients. During process development for the production of a recombinant IgG in a CHO cell line, we observed atypical high variability from 1 to 20% mAb aggregates formed during cell culture that negatively impacted antibody purification. Analytical characterization revealed the IgG aggregates were mediated by hydrophobic interactions likely caused by misfolded antibody during intracellular processing. Strikingly, data analysis showed an inverse correlation of lower cell culture temperature producing higher aggregate levels. All cultures at 37°C exhibited ≤ 5% aggregates at harvest. Aggregate levels increased 4-12-fold in 33°C cultures when compared to 37°C, with a corresponding 2-4-fold increase in heavy chain (HC) and light chain (LC) mRNA. Additionally, 37°C cases showed a greater excess of LC to HC mRNA levels. Endoplasmic reticulum (ER) chaperone expression and ER size also increased 25-75% at 33°C versus 37°C but to a lesser extent than LC and HC mRNA, consistent with a potential limiting ER folding capacity at 33°C for this cell line. Finally, we identified a 2-5-fold increase in mAb aggregate formation at 33°C compared to 37°C cultures for three additional CHO cell lines. Taken together, our observations indicate that low culture temperature can increase antibody aggregate formation in CHO cells by increasing LC and HC transcripts coupled with limited ER machinery.


MicroRNA and metabolomics signatures for adrenomyeloneuropathy disease severity.
Adrenomyeloneuropathy (AMN), the slow progressive phenotype of adrenoleukodystrophy (ALD), has no clinical plasma biomarker for disease progression. This feasibility study aimed to determine whether metabolomics and micro-RNA in blood plasma provide a potential source of biomarkers for AMN disease severity. Metabolomics and RNA-seq were performed on AMN and healthy human blood plasma. Biomarker discovery and pathway analyses were performed using clustering, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and regression against patient's clinical Expanded Disability Status Score (EDSS). Fourteen AMN and six healthy control samples were analyzed. AMN showed strong disease-severity-specific metabolic and miRNA clustering signatures. Strong, significant clinical correlations were shown for 7-alpha-hydroxy-3-oxo-4-cholestenoate (7-HOCA) (r 2 = 0.83, p < 0.00001), dehydroepiandrosterone sulfate (DHEA-S; r 2 = 0.82, p < 0.00001), hypoxanthine (r 2 = 0.82, p < 0.00001), as well as miRNA-432-5p (r 2 = 0.68, p < 0.00001). KEGG pathway comparison of mild versus severe disease identified affected downstream systems: GAREM, IGF-1, CALCRL, SMAD2&3, glutathione peroxidase, LDH, and NOS. This feasibility study demonstrates that miRNA and metabolomics are a source of potential plasma biomarkers for disease severity in AMN, providing both a disease signature and individual markers with strong clinical correlations. Network analyses of affected systems implicate differentially altered vascular, inflammatory, and oxidative stress pathways, suggesting disease-severity-specific mechanisms as a function of disease severity.


Large angioleiomyoma, rich of mast cell and sex hormone receptor expression.
Angioleiomyoma is a rare benign solitary tumor, arising from the vascular smooth muscle. This tumor usually occurs in the subcutis of extremities, uncommonly in abdomen, often presents as a small (<2 cm) and is treated with excision. We report an extremely rare case of unusually large angioleiomyoma, first diagnosed as an ovarian tumor with some malignant possibilities by diagnostic imaging. We resected 1.7 kg of tumor from the extra-peritoneal cavity in the lower abdomen. Histological study revealed that this case's angioleiomyoma had abundant mast cells and sex hormone receptor expression. This angioleiomyoma is not an obvious malignant tumor because of low mitosis, coagulative necrosis and cellular atypia. However, it seems to have low potential malignancy, because it has massive size, marked degeneration and abundant mast cells. There are some possibilities that sex hormones are related with the growth and degeneration of this case's tumor, because those receptors are strongly expressed in the nucleus of tumor cells.


A direct radioimmunoassay for estriol-16alpha-glucosiduronate: its use in the determination of plasma and urine levels and renal clearance of this conjugate in pregnancy.
A direct radioimmunoassay which does not require hydrolysis or chromatography has been developed for estriol-16alpha-glucosiduronate in pregnancy plasma and urine. The antigen used in the development of this antiserum was prepared by joining the carboxylic acid group of estriol-16alpha-glucosiduronate covalently to the epsilon-amino group of the lysine residues in bovine serum albumin. Results indicate that the direct radioimmunoassay yields levels of estriol-16alpha-glucosiduronate in late pregnancy urine that are comparable to those obtained by mroe elaborate procedures involving chromatographic separation of the estriol conjugates, followed by enzymic hydrolysis and measurement of the freed estriol. In addition, good correlation was found between the total estrogen values in urine obtained by currently used chemical procedures and urinary levels of estriol-16alpha-glucosiduronate. The renal clearance of estriol-16alpha-glucosiduronate was determined in eight normal women during the third trimester, and the mean value +/- S.D. was 404 +/- 81 ml. per minute (range, 248 to 494). This method is suitable for the evaluation of variations in the plasma and urine levels of estriol-16alpha-glucosiduronate in pregnancy and offers significant advantages over the presently used chemical methods for monitoring fetal well-being.


Concurrent Large Para-oesophageal Hiatal Hernia Repair and Laparoscopic Adjustable Gastric Banding: Results from 5-year Follow Up.
The objective of the study is to identify the efficacy and safety of combining laparoscopic adjustable gastric banding with repair of large para-oesophageal hernias. Para-oesophageal hernias are more common in the obese with higher recurrence rates following repair. The effect and safety of combining para-oesophageal hernia repair with laparoscopic adjustable gastric banding is unknown. One-hundred fourteen consecutive patients undergoing primary laparoscopic adjustable gastric banding with concurrent repair of a large para-oesophageal hernia were prospectively identified and matched to a control group undergoing primary laparoscopic adjustable gastric banding only. Weight loss and complication data were retrieved from a prospectively maintained database, and a standardised bariatric outcome questionnaire was used to assess post-operative symptoms, satisfaction with surgery and satiety scores. At a mean follow up of 4.9 ± 2.1 years, total weight loss was 16.4 ± 9.9% in the hernia repair group and 17.6 ± 12.6% in the control group (p = 0.949), with 17 vs. 11% loss to follow up rates (p = 0.246). No statistically significant difference in revisional surgery rate and symptomatic recurrence of hiatal hernia was documented in four patients in the hernia repair group (3.5%). No statistically significant difference in mean reflux (9.9 vs. 10.3, p = 0.821), dysphagia (20.7 vs. 20.1, p = 0.630) or satiety scores was identified. Concurrent repair of large para-oesophageal hiatal hernia and laparoscopic adjustable gastric banding placement is safe and effective both in terms of symptom control and weight loss over the intermediate term. In obese patients with large hiatal hernias, consideration should be given to combining repair of the hernia with a bariatric procedure.


Genomic alterations in human mesothelioma including high resolution mapping of common regions of DNA loss in chromosome arm 6q.
Molecular genetic analysis of 14 freshly resected human mesotheliomas was used to identify regions in the tumor genomes that display DNA copy number alterations, especially the regions that may harbor tumor suppressor genes. Three methods for molecular analysis were used, comparative genomic hybridization (CGH), loss of heterozygosity (LOH) and a new method, quantitative microsatellite analysis (QuMA). The most frequent alteration detected by CGH and LOH was deletion in chromosome 6q, for which QuMA was performed at 30 different loci so as to define the region(s) of common deletion(s). Our data indicates that there are three independent regions of common deletion, one of size 8.4 Mb located at 6q14, a second of size 15.9 Mb at 6q22 and a third of size 12.0 Mb at 6q24. This suggests that at least 3 tumor suppressor genes mapped to chromosome 6q are commonly involved in the pathogenesis of mesothelioma.


Induction of a zearalenone degrading enzyme caused by the substrate and its derivatives.
The Fusarium toxin zearalenone (ZON) is very harmful to animal and man due to its estrogenic effect, immunotoxicity and genotoxicity. Therefore, it is of high importance to establish a system for the detoxification of ZON. In large screening programmes, only the mycoparasiteGliocladium roseum (DSM 62726) was found to be capable of detoxifying ZON, by not yet characterized enzyme(s). It is the only known microorganism hydrolyzing the lactonic bond within the macrocyclic ring system of ZON. The resulting products are less toxic because they loose their estrogenic capacity. The extent of toxin degradation is enhanced when enzyme production inG roseum is induced by the substrate ZON itself and its derivatives. ZON and its derivatives differ in the ability to induce enzyme production. This was investigated underin vitro conditions. Differences were found in the required amount of the inducing substances and time optimum of induction in order to get maximal degradation of ZON. The regulation and biochemical properties of the enzyme are to be characterized as a prerequisite to develop applications aimed at the detoxification of ZON in food and feeding-stuff. Our aim is to isolate the unknown enzyme which is capable of the detoxification of this mycotoxin.


Chances for learning intraprofessional collaboration between residents in hospitals.
Intraprofessional collaboration (intraPC) between primary care (PC) doctors and medical specialists (MSs) is becoming increasingly important. Patient safety issues are often related to intraPC. In order to equip doctors well for their task of providing good quality and continuity of care, intraPC needs explicit attention, starting in postgraduate training. Worldwide, PC residents undertake a hospital placement during their postgraduate training, where they work in proximity with MS residents. This placement offers the opportunity to learn intraPC. It is yet unknown whether and how residents learn intraPC and what barriers to and opportunities for exist in learning intraPC during hospital placements. We performed an ethnographic non-participatory observational study in three emergency departments and three geriatric departments of five hospitals in the Netherlands. This was followed by 42 in-depth interviews with the observed residents and supervisors. The observations were used to feed the questions for the in-depth interviews. We analysed the interviews iteratively following the data collection using template analysis. Hospital wards are rich in opportunities for learning intraPC. These opportunities, however, are seldom exploited for various reasons: intraPC receives limited attention when formulating placement goals, so purposeful learning of intraPC hardly takes place; residents lack awareness of the learning of intraPC; MS residents are not accustomed to searching for expertise from PC residents; PC residents adapt to the MS role and they contribute very little of their PC knowledge, and power dynamics in the hospital department negatively influence the learning of intraPC. Therefore, improvements in mindset, professional identity and power dynamics are crucial to facilitate and promote intraPC. Intraprofessional collaboration is not learned spontaneously during hospital placements. To benefit from the abundant opportunities to learn intraPC, adjustments to the set-up of these placements are necessary. Learning intraPC is promoted when there is a collaborative culture, hierarchy is limited, and there is dedicated time for intraPC and support from the supervisor.


Kartogenin inhibits pain behavior, chondrocyte inflammation, and attenuates osteoarthritis progression in mice through induction of IL-10.
Osteoarthritis (OA) is a major degenerative joint condition that causes articular cartilage destruction. It was recently found that enhancement of chondroclasts and suppression in Treg cell differentiation are involved in the pathogenesis of OA. Kartogenin (KGN) is a small drug-like molecule that induces chondrogenesis in mesenchymal stem cells (MSCs). This study aimed to identify whether KGN can enhance severe pain behavior and improve cartilage repair in OA rat model. Induction of OA model was loaded by IA-injection of MIA. In the OA rat model, treatment an intra-articular injection of KGN. Pain levels were evaluated by analyzing PWL and PWT response in animals. Histological analysis and micro-CT images of femurs were used to analyze cartilage destruction. Gene expression was measured by real-time PCR. Immunohistochemistry was analyzed to detect protein expression. KGN injection significantly decreased pain severity and joint destruction in the MIA-induced OA model. KGN also increased mRNA levels of the anti-inflammatory cytokine IL-10 in OA patients' chondrocytes stimulated by IL-1β. Decreased chondroclast expression, and increased Treg cell expression. KGN revealed therapeutic activity with the potential to reduce pain and improve cartilage destruction. Thus, KGN could be a therapeutic molecule for OA that inhibits cartilage damage.


Mesopourous Fe3O4@SiO2-hydroxyapatite nanocomposite: Green sonochemical synthesis using strawberry fruit extract as a capping agent, characterization and their application in sulfasalazine delivery and cytotoxicity.
The present study introduces a simple, biocompatible and effective drug delivery system by using mesoporous nanocomposite-based platform. To achieve this goal, mesopourous Fe3O4@SiO2-hydroxyapatite nanocomposite (mFSH) was synthesized by sonochemical process in presence of strawberry fruit extract as capping agent (mFSH-SW). The impact of various factors such as sonication time (5, 15, 30 and 45 min), capping agent (cherry (CH), strawberry (SW), malus domestica (MD), andean blackberry (AB)), pH (10, 11 and 12) and sonication power (30, 60 and 80 W) were investigated to reach optimum condition. To reach high efficiency of drug loading, mFSH was grafted with 3-aminopropyl triethoxysilane (APTES). Uniform, regular and spherical morphology of nanocomposite were specified by field emission scanning electron microscopy (FESEM), X-ray powder diffraction (XRD), vibrating sample magnetometer (VSM), high-resolution transmission electron microscopy (HRTEM), energy-dispersive x-ray spectroscopy (EDX), dynamic light scattering (DLS), nitrogen adsorption/desorption isotherm and Fourier-transform infrared spectroscopy (FT-IR) techniques. The mean pore size, surface area, and pore volume of mFSH-SW were 63.2 m2 g-1, 14.1 nm and 0.24 cm3 g-1, respectively. Sulfasalazine (SLN) loading and release were carried out by various products. The functionalized mFSH-SW showed high adsorption capacity (approximately 59.1 %) for SLN that possesses amino functional groups. The results showed that 100 % of SLN-loaded nanocomposite could be released after 36 h at intestinal conditions (pH = 6.8). In addition, in-vitro and in-vivo toxicity investigations of product were performed with apoptosis/necrosis, XTT and pathology assay, respectively. All in all, unique properties of the nanocomposite including low toxicity, high drug loading, slow release and biodegradable showed that it can be used in biomedical sciences.


Mast cell receptors controlling histamine release: influences on the mode of action of drugs used in the treatment of adverse drug reactions.
In drug-induced allergic diseases of the immediate type (anaphylactic and anaphylactoid reactions), the primary target cells are tissue mast cells, which discharge their granular content upon interaction with different secretagogues (immunological releasers; histamine liberators) on specific plasma membrane receptors. Experiments are reviewed here which report that IgE-mediated histamine release from mast cells, and the secretion of histamine induced by non-immunological secretagogues (dextran; compound 48/80; acetylcholine) are blocked by beta-adrenoceptor and H2-receptor agonists, their inhibiting effect being surmountable by beta-adrenoceptor blocking drugs and by anti-H2-antihistamines. Specific radioligands ([3H]-dihydroalprenolol; [3H]-cimetidine) binding to rat mast cell membranes points to the possibility that inhibition of histamine release is brought about by the activation of mast cell beta-adrenoceptors and H2-receptors. Drugs used in therapy of anaphylactic or anaphylactoid reactions may act either on tissue receptors, competing with released mediators, or by inhibiting the release of allergic mediators from mast cells, on activation of specific receptors located in mast cell plasma membranes.


Global positioning system: a new tool to measure the distribution of anemia and nutritional status of children (5-10 years) in a rural area in south India.
Global positioning system (GPS) is a satellite-based navigation system that is of late being used in health care. The aims of the study were to describe the geographical distribution and assess the prevalence of anemia and malnutrition in children aged 5-10 years with GPS. This exploratory study was conducted over a period of 2 months in the rural field practice area of a medical college situated in Bangalore during June-July 2012. Children aged 5-10 years were the study subjects. GPS was used for describing the geographical distribution of anemia and nutrition status on the Google earth map. The prevalence of anemia in the study subjects was 8.7%. The prevalence of underweight, stunting, thinness, and severe thinness among the study subjects was 52.8%, 28.5%, 23.5%, and 29.1%, respectively; however, overweight and obesity were observed only in 0.9% and 1.2% of the study subjects, respectively. GPS was easy to use and was able to demonstrate the actual distribution of morbidity at the household level in the rural area.


The Impact of Scripted Self-Hypnotic Relaxation on the Periprocedural Experience and Anesthesiologist Sedation Use in the Pediatric Cardiac Catheterization Suite: A Prospective Randomized Controlled Trial.
To assess the impact on children of self-hypnotic relaxation scripts read by trained staff prior to the induction of anesthesia and/or extubation on the periprocedural experience. A total of 160 children aged 7-18 years undergoing a cardiac catheterization intervention under general anesthesia were randomized into 4 groups: (1) a pre-procedure (PP-script) read prior to entering the procedural room, (2) a script read prior to extubation (PX-Script), (3) both PP- and PX-Scripts read and (4) no script read. Anxiety and pain were rated on self-reported 0-10 scales. The modified Yale Preoperative Anxiety Scale was used for preoperative anxiety. The effect of script reading was associated with outcomes by linear regression for continuous variables, and logistic regression for binary variables in two-sided tests at a significance level of 0.05. Results are given in odds ratios (OR) and 95% confidence intervals (CI). Data were available for 158 patients. Reading the PP-Script prior to anesthesia was associated with a significant reduction in the use of intraoperative sedatives from 30% to 14% (OR 0.40; CI 0.18-0.88; p = 0.02) by the anesthesiologists, who were blinded to group attribution until extubation. This was despite the children not self-reporting significantly lower levels of anxiety or pain. The PX-Script did not change outcomes. Among groups, there was no significant difference in room time, postoperative recovery time and pain. Reading a PP-Script for guidance in self-hypnotic relaxation can result in less need for intravenous sedation in the judgment of the anesthesiologist, independent of the children's self-reported anxiety and pain. This raises interesting questions about subconscious patient-physician interactions affecting pain management. NCT02347748.


A model for simultaneous crystallisation and biodegradation of biodegradable polymers.
This paper completes the model of biodegradation for biodegradable polymers that was previously developed by Wang et al. (Wang Y, Pan J, Han X, Sinka, Ding L. A phenomenological model for the degradation of biodegradable polymers. Biomaterials 2008;29:3393-401). Crystallisation during biodegradation was not considered in the previous work which is the topic of the current paper. For many commonly used biodegradable polymers, there is a strong interplay between crystallisation and hydrolysis reaction during biodegradation - the chain cleavage caused by the hydrolysis reaction provides an extra mobility for the polymer chains to crystallise and the resulting crystalline phase becomes more resistant to further hydrolysis reaction. This paper presents a complete theory to describe this interplay. The fundamental equations in the Avrami's theory for crystallisation are modified and coupled to the diffusion-reaction equations that were developed in our previous work. The mathematical equations are then applied to three biodegradable polymers for which long term degradation data are available in the literature. It is shown that the model can capture the behavior of the major biodegradable polymers very well.


Clinical features and high-risk indicators of central nervous system involvement in primary Sjögren's syndrome.
Evidence for central nervous system involvement in primary Sjögren's syndrome (pSS) patients is controversial and extremely limited. We aimed to describe the clinical profiles and high-risk indicators of primary Sjögren's syndrome (pSS) patients with central nervous system (CNS) involvement (pSS-CNS). A total of 412 participants with pSS from a hospital in China from January 2012 to December 2019 were enrolled in the retrospective study. 42 pSS-CNS patients were compared with 370 pSS patients without CNS involvement. The clinical features, laboratory examinations, imaging characteristics, and treatment of the pSS-CNS cases were systematically analyzed. Potential risk factors related to pSS-CNS patients were identified by multivariate logistic regression analysis. The prevalence of central nervous system involvement in the studied pSS patients was 10.2% (42/412), with 31.3% (14/42) of pSS patients having neurological manifestations as the initial symptom. The manifestations of hemiparesis (35.7%, 15/42), paraparesis (28.6%, 12/42), dysphonia (31.0%, 13/42), blurred vision (21.4%, 9/42), and dysfunctional proprioception (23.8%, 10/42) were more common in the pSS-CNS patients. Cerebral infarction (57.1%, 24/42), demyelination (31.0%, 13/42), myelitis (23.8%, 11/42), and angiostenosis (21.4%, 9/42) were most often found on MRI or CT scan imaging in the pSS-CNS patients. Intrathecal IgG level and total protein of cerebrospinal fluid were increased in 50% (8/16) of the pSS-CNS group. In comparison with patients without CNS involvement, the pSS-CNS patients were found to also have kidney and lung involvement, hematologic abnormalities, positive ANA and anti-SSA antibody tests, and reduced complement 3 (C3) and complement 4 (C4) levels (all p < 0.05). The prevalence of lung involvement, immune thrombocytopenia, and high-titer ANA (1:1000) were significantly higher in pSS-CNS disease activity compared to those in the moderately active group. Multivariate analysis identified lung involvement, anti-SSA positivity, and low C3 levels as prognostic factors for pSS-CNS. After high-dose glucocorticoids and immunosuppressive therapy, 60.5% (26/38) of pSS-CNS patients improved, 36.8% (14/38) were unresponsive to treatment, and 2.6% (1/38) died. Clinical features are diverse in pSS-CNS patients, and the morbidity rate is low. CNS involvement was the initial presentation in state percentage here pSS patients. Pulmonary involvement, a positive anti-SSA antibody test, and reduced C3 levels are potential risk factors for CNS involvement in pSS. Treatment with high-dose glucocorticoids and immunosuppressive therapy appeared effective in 60% of pSS-CNS patients. Key Points • The CNS manifestations of pSS are diverse, and CNS imaging and CSF analysis are important for the diagnosis. • Pulmonary involvement, positive anti-SSA, and reduced C3 levels are potential risk factors of pSS-CNS. • About 60% of pSS-CNS patients were responsive to high-dose glucocorticoid administration and immunosuppressive therapy.


Differences and commonalities in the judgment of causality in physical and social contexts: an fMRI study.
Understanding cause and effect is a fundamental aspect of human cognition. When shown videos of simple two-dimensional shapes colliding, humans experience one object causing the other to move, e.g., one billiard-like ball seeming to hit and move the other. The impression of causality can also occur when people attribute social interactions to moving objects. Whether the judgment of social and physical causality engages distinct or shared neural networks is not known. In a functional magnetic imaging (fMRI) study, participants were presented with two types of dynamic videos: a blue ball colliding with a red ball (P; physical condition) and a blue ball ("Mr. Blue") passing a red ball ("Mrs. Red") without making contact (S; social condition). Participants judged causal relationships (C) or movement direction (D; control task) in both video types, resulting in four conditions (PC; SC; PD; SD). We found common neural activations for physical and social causality judgments (SC > SD)∩(PC > PD) in the right middle/inferior frontal gyrus, right inferior parietal lobule, the right supplementary motor area, and bilateral insulae. For social causal judgments (SC > PC), we found distinct neural activity in the right temporo-parietal junction (rTPJ). These results provide evidence for a common neural network underlying judgments of causality that apply to both physical and social situations. The results also indicate that social causality judgments recruit additional neural resources in an area critical for determining animacy and intentionality.


T cell proliferation in Mycobacterium lepraemurium infection. I. Lack of correlation between antigen-specific proliferation of Lyt 1 + 23- cells and resistance in lethal infections.
Antigen specific T lymphocyte proliferation and Lyt phenotypes of the T lymphocytes were studied in BALB/c and C57BL/6 mice infected with 10(9) M. lepraemurium organisms intravenously. A highly disseminated form of the disease developed to which all mice succumbed by 17 weeks. Maximal antigen-specific T lymphocyte proliferation was detected at 4 weeks after the infection and persisted thereafter even when the mice started to die of the infection. Accessory cells of phagocytic and adherent type did not appear to be a requirement for this proliferation. The T lymphocytes generated during the course of the infection were mostly of the Lyt 1 phenotype. However, there appeared to be no correlation between sensitized Lyt 1 cells capable of antigen-induced T lymphocyte proliferation and protective immunity.


Radiologic diagnosis of pain in the athlete.
This article provides an overview of the various radiographic procedures available today. The correct indications for the use of each of these is emphasized and illustrated.


Assessment of contraceptive needs in women undergoing bariatric surgery.
To evaluate documentation of contraception and counseling in women planning to undergo bariatric surgery. Chart review of 1012 women ages 18-45years presenting for bariatric surgery evaluation. Data on socio-demographic variables, documented contraceptive method, preconception counseling, gynecology referrals and postoperative pregnancies were collected. The charts of only 272 women (26.9%) contained documentation of a contraceptive method; the most common was oral contraceptives (n=132, 48.5%). Sixteen pregnancies were identified in the first 18months postoperatively. Currently, the documentation of contraceptive counseling is lacking in clinical practice. Measures to enhance provider and patient awareness of these issues will improve patient care. Pregnancy planning and documentation of perioperative contraceptive use in women undergoing bariatric surgery are suboptimal, placing these women at risk of unintended pregnancies. Future research should delineate the best practices in contraceptive provision in this high-risk population of women.


Shifting attention does not influence numerical processing.
Many theories of numerical cognition assume that numbers and space share a common representation at the response level. For example, observers are faster to respond to small numbers with their left hand and large numbers with their right hand (the SNARC effect). There is also evidence that viewing numbers can produce spatial shifts of attention, suggesting that attention may play a role in the spatial representation of numbers. In the present study, we assessed whether shifts of attention can influence numerical processing. Participants viewed a leftward or rightward peripheral cue followed by a centrally presented number, then judged whether the number was odd or even. Participants responded faster and made fewer errors when the number magnitude and response side were compatible, revealing a response-based SNARC effect. Participants also responded faster when the cue direction and response side were compatible, revealing a Simon effect. However, participants did not respond faster when the cue direction and number magnitude were compatible. Similar findings were observed when the association between numbers and space was relatively explicit. Moreover, although we failed to observe a response-based SNARC effect when number magnitude was directly relevant to observers' task, we observed a large Simon effect. Together, these findings suggest that although numbers and space share a common representation at the response level, attention does not play a substantial role in the spatial representation of numbers.


Increasing the spectral shifts in LSPR biosensing using DNA-functionalized gold nanorods in a competitive assay format for the detection of interferon-γ.
We demonstrate an approach that utilizes DNA-functionalized gold nanorods (AuNRs) in an indirect competitive assay format to increase the spectra shift in localized surface plasmon resonance (LSPR) biosensing. We use interferon gamma (IFN-γ) as a model analyte to demonstrate the feasibility of our detection method. The LSPR chips with periodic gold nanodot arrays are fabricated using a thermal lithography process and are functionalized with IFN-γ aptamers for detection. The DNA-functionalized AuNRs and IFN-γ compete with each other to bind to the aptamers during detection, and the spectra shifts are mainly caused by the AuNRs rather than IFN-γ. When using our approach, the target molecules do not need to be captured by two capture ligands simultaneously during detection and thus do not require multiple binding sites. Both experiments and finite-difference time-domain (FDTD) simulations show that making the AuNRs as close to the chip surface as possible is very critical for increasing LSPR shifts, and the simulated results also show that the orientation of the AuNR affects the plasmon coupling between the gold nanodots on the chip surface and the nearby AuNRs. Although only the detection of IFN-γ is demonstrated in this study, we expect that the LSPR biosensing method can be applied to label-free detection of a variety of molecules as long as suitable aptamers are available.


Understanding the genomic selection for crop improvement: current progress and future prospects.
Although increased use of modern breeding techniques and technology has resulted in long-term genetic gain, the pace of genetic gain must be sped up to satisfy global agricultural demand. However, marker-assisted selection has proven its potential for improving qualitative traits with large effects regulated by one to few genes. Its contribution to the improvement of the quantitative traits regulated by a number of small-effect genes is modest. In this context, genomic selection (GS) has been regarded as the most promising method for genetically enhancing complicated features that are regulated by several genes, each of which has minor effects. By examining a population's phenotypes and high-density marker scores, genomic selection can forecast the breeding potential of individual lines. The fact that GS uses all marker data in the prediction model prevents skewed marker effect estimations and maximizes the amount of variation caused by small-effect QTL. It has the ability to speed up the breeding cycle and as a consequence of which superior genotypes are selected rapidly. Developing the best GS models while taking into account non-additive effects, genotype-by-environment interaction, and cost-effectiveness will enable the widespread implementation of GS in plants. These steps will also increase heritability estimation and prediction accuracy. This review focuses on the shift from conventional selection methods to GS, underlying statistical tools and methodologies, the state of GS research in agricultural plants, and prospects for its effective use in the creation of climate-resilient crops.


Chemoproteomic identification of a DPP4 homolog in Bacteroides thetaiotaomicron.
Serine hydrolases have important roles in signaling and human metabolism, yet little is known about their functions in gut commensal bacteria. Using bioinformatics and chemoproteomics, we identify serine hydrolases in the gut commensal Bacteroides thetaiotaomicron that are specific to the Bacteroidetes phylum. Two are predicted homologs of the human dipeptidyl peptidase 4 (hDPP4), a key enzyme that regulates insulin signaling. Our functional studies reveal that BT4193 is a true homolog of hDPP4 that can be inhibited by FDA-approved type 2 diabetes medications targeting hDPP4, while the other is a misannotated proline-specific triaminopeptidase. We demonstrate that BT4193 is important for envelope integrity and that loss of BT4193 reduces B. thetaiotaomicron fitness during in vitro growth within a diverse community. However, neither function is dependent on BT4193 proteolytic activity, suggesting a scaffolding or signaling function for this bacterial protease.


Implications of the Affordable Care Act on Surgery and Cancer Care.
The Patient Protection and Affordable Care Act increased health insurance coverage to millions in the United States, transformed both the private and public insurance markets, and invested in care delivery changes in an attempt to increase the quality and value of health care. How these changes have translated to improved long-term oncologic outcomes, including for survivorship, remains to be seen. Newer models of payment and care delivery attempt to improve both short-term and long-term quality while better controlling cost trends. The extent to which cancer care delivery will be affected also needs further study and optimization.


Cellular adaptations leading to coral fragment attachment on artificial substrates in Acropora millepora (Am-CAM).
Reproductive propagation by asexual fragmentation in the reef-building coral Acropora millepora depends on (1) successful attachment to the reef substrate through modification of soft tissues and (2) a permanent bond with skeletal encrustation. Despite decades of research examining asexual propagation in corals, the initial response, cellular reorganisation, and development leading to fragment substrate attachment via a newly formed skeleton has not been documented in its entirety. Here, we establish the first "coral attachment model" for this species ("Am-CAM") by developing novel methods that allow correlation of fluorescence and electron microscopy image data with in vivo microscopic time-lapse imagery. This multi-scale imaging approach identified three distinct phases involved in asexual propagation: (1) the contact response of the coral fragment when contact with the substrate, followed by (2) fragment stabilisation through anchoring by the soft tissue, and (3) formation of a "lappet-like appendage" structure leading to substrate bonding of the tissue for encrustation through the onset of skeletal calcification. In developing Am-CAM, we provide new biological insights that can enable reef researchers, managers and coral restoration practitioners to begin evaluating attachment effectiveness, which is needed to optimise species-substrate compatibility and achieve effective outplanting.


Obtaining of 24-Norchol-4-ene-3,22-dione from Phytosterol with Mutants of Mycolicibacterium neoaurum.
Engineered mutants of Mycolicibacterium spp. are known producers of valuable steroid synthons with C19 or C22 skeleton. Here we describe a method for site-directed mutagenesis of Mycolicibacterium neoaurum strains, bioconversion from phytosterol, and selective purification of C23 steroid 24-norchol-4-ene-3,22-dione (24-NCED) and C22 steroid 20-hydroxymethylpregn-4-ene-3-one (20-HMP). The yields of crystalline products with 95% purity by the method here described are 2.74 ± 0.085 g for 24-NCED and 1.42 ± 0.085 g for 20-HMP from 10 g/L phytosterol. 20-HMP is recognized as the key precursor in chemical syntheses of pharmaceutical corticosteroids and 24-NCED is a promising synthon for the synthesis of valuable steroids and own potent biological activity.


[Migrant children: healthcare in a transcultural setting].
Children of migrants develop and grow up with two languages, that of their family and that learnt at school, and within the two corresponding worlds. This transcultural situation entails a degree of vulnerability, and these children need to learn to reconcile the two worlds. In the setting of care, these different worlds and languages should be taken into account for what they are. This is an ethical requirement, and also a pragmatic approach, contributing to the efficacy of the care of these children. In this article we analyse the factors to take into account for all to provide adequate care for children of migrants, and we explore the modes of referral to specialised transcultural consultations if necessary.


Reproducibility of DCE-MRI time-intensity curve-shape analysis in patients with knee arthritis: A comparison with qualitative and pharmacokinetic analyses.
To compare the between-session reproducibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) combined with time-intensity curve (TIC)-shape analysis in arthritis patients, within one scanner and between two different scanners, and to compare this method with qualitative analysis and pharmacokinetic modeling (PKM). Fifteen knee joint arthritis patients were included and scanned twice on a closed-bore 1.5T scanner (n = 9, group 1), or on a closed-bore 1.5T and on an open-bore 1.0T scanner (n = 6, group 2). DCE-MRI data were postprocessed using in-house developed software ("Dynamo"). Disease activity was assessed. Disease activity was comparable between the two visits. In group 1 qualitative analysis showed the highest reproducibility with intraclass correlation coefficients (ICCs) between 0.78 and 0.98 and root mean square-coefficients of variation (RMS-CoV) of 8.0%-14.9%. TIC-shape analysis showed a slightly lower reproducibility with similar ICCs (0.78-0.97) but higher RMS-CoV (18.3%-42.9%). The PKM analysis showed the lowest reproducibility with ICCs between 0.39 and 0.64 (RMS-CoV 21.5%-51.9%). In group 2 TIC-shape analysis of the two most important TIC-shape types showed the highest reproducibility with ICCs of 0.78 and 0.71 (RMS-CoV 29.8% and 59.4%) and outperformed the reproducibility of the most important qualitative parameter (ICC 0.31, RMS-CoV 45.1%) and the within-scanner reproducibility of PKM analysis. TIC-shape analysis is a robust postprocessing method within one scanner, almost as reproducible as the qualitative analysis. Between scanners, the reproducibility of the most important TIC-shapes outperform that of the most important qualitative parameter and the within-scanner reproducibility of PKM analysis.


SulP, a nuclear gene encoding a putative chloroplast-targeted sulfate permease in Chlamydomonas reinhardtii.
Genomic, proteomic, phylogenetic and evolutionary aspects of a novel gene encoding a putative chloroplast-targeted sulfate permease of prokaryotic origin in the green alga Chlamydomonas reinhardtii are described. This nuclear-encoded sulfate permease gene (SulP) contains four introns, whereas all other known chloroplast sulfate permease genes lack introns and are encoded by the chloroplast genome. The deduced amino acid sequence of the protein showed an extended N-terminus, which includes a putative chloroplast transit peptide. The mature protein contains seven transmembrane domains and two large hydrophilic loops. This novel prokaryotic-origin gene probably migrated from the chloroplast to the nuclear genome during evolution of C. reinhardtii. The SulP gene, or any of its homologues, has not been retained in vascular plants, e.g. Arabidopsis thaliana, although it is encountered in the chloroplast genome of a liverwort (Marchantia polymorpha). A comparative structural analysis and phylogenetic origin of chloroplast sulfate permeases in a variety of species is presented.


Surgical treatment of thoracolumbar fracture with incomplete lower limb paralysis in a patient with COVID-19.
Since December 2019, COVID-19, an acute infectious disease, has gradually become a global threat. We report a case of thoracolumbar fractures (T12 and L1) and incomplete lower limb paralysis in a patient with COVID-19. After a series of conservative treatment which did not work at all, posterior open reduction and pedicle screw internal fixation of the thoracolumbar fracture were performed in Wuhan Union Hospital. Three weeks later, the patient could stand up and the pneumonia is almost cured. We successfully performed a surgery in a COVID-19 patient, and to our knowledge it is the first operation for a COVID-19 patient ever reported.


Quality Improvement in Neurocritical Care.
Quality improvement is key to advancing outcomes for neurocritically ill patients. Variation in neurocritical care practice can lead to differences in health outcomes and contribute to health disparities. The implementation of evidence-based best practice standards represents a major opportunity to improve their care. Neurocritical care performance measures have recently been developed and may be used to target high priority areas for improvement. In addition, neurocritical care clinicians should be aware of the heavily weighted pay-for-performance and publicly reported performance measures that are directly relevant to neurocritical care practice.


Computational Modeling for Enhancing Soft Tissue Image Guided Surgery: An Application in Neurosurgery.
With the recent advances in computing, the opportunities to translate computational models to more integrated roles in patient treatment are expanding at an exciting rate. One area of considerable development has been directed towards correcting soft tissue deformation within image guided neurosurgery applications. This review captures the efforts that have been undertaken towards enhancing neuronavigation by the integration of soft tissue biomechanical models, imaging and sensing technologies, and algorithmic developments. In addition, the review speaks to the evolving role of modeling frameworks within surgery and concludes with some future directions beyond neurosurgical applications.


Protein conformer selection by sequence-dependent packing contacts in crystals of 3-phosphoglycerate kinase.
In several crystal structures of 3-phosphoglycerate kinase (PGK), the two domains occupy different relative positions. It is intriguing that the two extreme (open and closed) conformations have never been observed for the enzyme from the same species. Furthermore, in certain cases, these different crystalline conformations represent the enzyme-ligand complex of the same composition, such as the ternary complex containing either the substrate 3-phosphoglycerate (3-PG) and beta,gamma-imido-adenosine-5'-triphosphate (AMP-PNP), an analogue of the substrate MgATP, or 3-PG and the product MgADP. Thus, the protein conformation in the crystal is apparently determined by the origin of the isolated enzyme: PGK from pig muscle has only been crystallized in open conformation, whereas PGK from either Thermotoga maritima or Trypanosoma brucei has only been reported in closed conformations. A systematic analysis of the underlying sequence differences at the crucial hinge regions of the molecule and in the protein-protein contact surfaces in the crystal, in two independent pairs of open and closed states, have revealed that 1) sequential differences around the molecular hinges do not explain the appearance of fundamentally different conformations and 2) the species-specific intermolecular contacts between the nonconserved residues are responsible for stabilizing one conformation over the other in the crystalline state. A direct relationship between the steric position of the contacts in the three-dimensional structure and the conformational state of the protein has been demonstrated.


Effect of incremental exercise on initiation and movement times in a choice response, whole body psychomotor task.
To examine how exercise at moderate and maximal intensities affects performance on a choice response time, whole body psychomotor task. Subjects (n = 12) were tested on a three-choice response time task, after rest and after exercise at 70% and 100% maximum power output (W*max). The dependent variables were time to begin forward momentum (initiation time) and time to complete the movement (movement time). Stride time for the first and second strides and number of strides to cover first 1.1 m were also measured. Blood lactate concentrations and heart rate were recorded before and after completion of each psychomotor test. The subjects subjectively assessed the amount of effort that they used to complete the task. Repeated measures analysis of variance showed a significant effect for initiation (F2,22 = 11.47, p < 0.001) and movement times (F2,22 = 14.61, p < 0.001). Post hoc least significant difference (LSD) tests showed that initiation time after exercise at 70% W*max was significantly faster than that in the other two conditions. Speed of initiation after rest was significantly quicker than that after exercise at W*max. For movement time, LSD tests showed that time after maximal exercise was significantly slower than that in the other two conditions. Stride time for the second stride showed a significant effect (F2,22 = 6.20, p < 0.01). LSD tests found that time after exercise at W*max was significantly slower in the other two conditions. Stepwise multiple regression analyses found that the increment of change, from rest, of lactate concentrations could significantly predict the increment of change in initiation (R2 = 0.40) and movement (R2 = 0.50) times. Exercise affects a whole body task differently from purely cognitive tasks. Central factors are probably more important than peripheral factors.


Glutamatergic dysfunction, neuroplasticity, and redox status in the peripheral blood of patients with motor conversion disorders (functional movement disorders): a first step towards potential biomarkers discovery.
Functional movement disorders (FMD) are characterized by the presence of neurological symptoms that cannot be explained by typical neurological diseases or other medical conditions. First evidence showed that, compared to healthy controls (CTR), FMD patients presented increased levels of glutamate+glutamine in the anterior cingulate cortex/medial prefrontal cortex, and decreased levels of glutamate in the cerebrospinal fluid, suggesting that a glutamatergic dysfunction might play a role in FMD pathophysiology. In this study, 12 FMD patients and 20 CTR were recruited and underwent venous blood sampling and urine collection: levels of glutamate, BDNF, dopamine, oxidative stress, creatinine, neopterin, and uric acid were analyzed. Participants also underwent a psychometric assessment investigating depression, anxiety, and alexithymia. We found that levels of glutamate, BDNF, and dopamine were significantly lower in the blood of FMD patients than CTR. Glutamate and dopamine levels were positively associated with levels of alexithymia. Our findings give further evidence that glutamatergic dysfunction might be involved in the pathophysiology of FMD, possibly representing a biomarker of disease; moreover, since glutamatergic and dopaminergic systems are closely interconnected, our results might have a relevance in terms of treatment options for FMD patients.


[Effects of a 6F urethral catheter on uroflowmetry in men with benign prostatic hypertrophy].
To determine whether the presence of a 6F catheter in the urethra modifies uroflowmetric parameters in a population of men with benign prostatic hyperplasia. 260 patients, 45 to 86 years old, presenting with benign prostatic hyperplasia, underwent two uroflowmetries, one with the urethra free, the other with a 6F urethral catheter. Patients with a history of neurological disease, diabetes mellitus, prostatic cancer, lower urinary tract surgery or taking drugs likely to affect micturition, were excluded from the study. Maximum flow rate (Qmax) and voided volume were then compared during the 2 recordings, using Wilcoxon's non parametric test. No significant difference was observed between voided volumes in the 2 groups (m: 207 ml versus m: 226 ml), but a very significant difference was observed for maximum flow rate measurements (m: 8.62 ml/s versus m: 6.97 ml/s p = 0.0001). The presence of an urethral catheter, even small calibre (6F), modifies the flow rate by more than 1.5 ml/s. This element must be taken into account when performing and interpreting measurements of the pressure-flow relationship in men.


A data quality assessment of the first four years of malaria reporting in the Senegal DHIS2, 2014-2017.
As the global burden of malaria decreases, routine health information systems (RHIS) have become invaluable for monitoring progress towards elimination. The District Health Information System, version 2 (DHIS2) has been widely adopted across countries and is expected to increase the quality of reporting of RHIS. In this study, we evaluated the quality of reporting of key indicators of childhood malaria from January 2014 through December 2017, the first 4 years of DHIS2 implementation in Senegal. Monthly data on the number of confirmed and suspected malaria cases as well as tests done were extracted from the Senegal DHIS2. Reporting completeness was measured as the number of monthly reports received divided by the expected number of reports in a given year. Completeness of indicator data was measured as the percentage of non-missing indicator values. We used a quasi-Poisson model with natural cubic spline terms of month of reporting to impute values missing at the facility level. We used the imputed values to take into account the percentage of malaria cases that were missed due to lack of reporting. Consistency was measured as the absence of moderate and extreme outliers, internal consistency between related indicators, and consistency of indicators over time. In contrast to public facilities of which 92.7% reported data in the DHIS2 system during the study period, only 15.3% of the private facilities used the reporting system. At the national level, completeness of facility reporting increased from 84.5% in 2014 to 97.5% in 2017. The percentage of expected malaria cases reported increased from 76.5% in 2014 to 94.7% in 2017. Over the study period, the percentage of malaria cases reported across all districts was on average 7.5% higher (P < 0.01) during the rainy season relative to the dry season. Reporting completeness rates were lower among hospitals compared to health centers and health posts. The incidence of moderate and extreme outlier values was 5.2 and 2.3%, respectively. The number of confirmed malaria cases increased by 15% whereas the numbers of suspected cases and tests conducted more than doubled from 2014 to 2017 likely due to a policy shift towards universal testing of pediatric febrile cases. The quality of reporting for malaria indicators in the Senegal DHIS2 has improved over time and the data are suitable for use to monitor progress in malaria programs, with an understanding of their limitations. Senegalese health authorities should maintain the focus on broader adoption of DHIS2 reporting by private facilities, the sustainability of district-level data quality reviews, facility-level supervision and feedback mechanisms at all levels of the health system.


[Art, mental health, and public healthcare: profile of a care culture in the history of São Paulo city].
By studying the inclusion of artistic and cultural activities in the care provided throughout the history of public mental healthcare in greater São Paulo, Brazil, we can better understand and characterize the practices adopted in the Psychosocial Care Centers in the city today. Experiments carried out between the 1920s and 1990s are investigated, based on bibliographic research. The contemporary data were obtained from research undertaken at 126 workshops at 21 Psychosocial Care Centers in the same city between April 2007 and April 2008. The findings indicate that the current trend in mental healthcare, whose clinical perspective spans the realms of art and mental health and has territorial ramifications, has maintained some of the features encountered in earlier mental healthcare experiments.


Computational fluid dynamic simulations for dispersion of nanoparticles in a magnetohydrodynamic liquid: a Galerkin finite element method.
This investigation studies the effects of the thermo-physical properties of four types of nano-metallic particles on the thermo-physical properties of radiative fluid in the presence of buoyant forces and Joule heating (ohmic dissipation). The Galerkin finite element algorithm is used to perform computations and simulated results are displayed in order to analyze the behavior of velocity and temperature of copper, silver, titanium dioxide and aluminum oxide-nanofluids. All the simulations are performed with η max = 6 computational tolerance 10-6 for 200 elemental discretizations. Due to the dispersion of nano-sized particles in the base fluid, an increase in the thermal conduction is noticed. This study also predicts future improvements in the thermal systems. Due to magnetic field and fluid flow interaction, the electrical energy converts into heat. This is undesirable in many thermal systems. Therefore, control of Joule heating in the design of thermos systems is necessary. However, this dissipation of heat may be desirable in some biological fluid flows. An increase in energy losses is noted as magnetic intensity is increased.


Ultrasound-assistant preparation of Cu-SAPO-34 nanocatalyst for selective catalytic reduction of NO by NH3.
The influence of the various preparation methods of Cu-SAPO-34 nanocatalysts on the selective catalytic reduction of NO with NH3 under excess oxygen was studied. Cu-SAPO-34 nanocatalysts were prepared by using four techniques: conventional impregnation (IM), ultrasound-enhanced impregnation (UIM), conventional deposition precipitation (DP) using NaOH and homogeneous deposition precipitation (HDP) using urea. These catalysts were characterized in detail by various techniques such as N2-sorption, XRD, TEM, H2-TPR, NH3-TPD and XPS to understand the catalyst structure, the nature and the dispersed state of the copper species, and the acid sites for NH3 adsorption. All of the nanocatalysts showed high activities for NO removal. However, the activities were different and followed the sequence of Cu-SAPO-34 (UIM)>Cu-SAPO-34 (HDP)>Cu-SAPO-34 (IM)>Cu-SAPO-34 (DP). Based on the obtained results, it was concluded that the NO conversion on Cu-SAPO-34 nanocatalysts was mainly related to the high reducibility of the isolated Cu(2+) ions and CuO species, the number of the acid sites and the dispersion of CuO species on SAPO-34.


Laparoscopic staging for apparent early stage ovarian or fallopian tube cancer. First case series from a UK cancer centre and systematic literature review.
To describe the experience of laparoscopic staging of apparent early stage adnexal cancers. Prospectively collected data on women who had laparoscopic staging for apparent early stage adnexal cancers from May 2008 to September 2012 was reviewed. All women had had a prior surgical procedure at which the diagnosis was made, without comprehensive staging. A systematic MEDLINE search from 1980 to 2012 for publications on laparoscopic staging was performed. Thirty-five women had laparoscopic staging. Median age was 45 years (range 21-73). Median operative time was 210 min (range 90-210). Four intra-operative and one post-operative complication occurred; overall complication rate 5/35 (14%). One vena cava and one transverse colon injury underwent laparotomies for repair. Laparotomy conversion rate 2/35 (6%). Following laparoscopic staging, the cancer was upstaged for eight (23%) women; microscopic omental involvement (four women), pelvic lymph node involvement (two women), para-aortic lymph node involvement (one woman) and contra-lateral ovarian involvement (one woman). After follow up for a median of 18 months (range 3-59) the disease free survival was 94% and overall survival was 100%. Nine studies were identified on laparoscopic staging of adnexal cancer, of which this is the largest single institution series. This study adds to the evidence that laparoscopic staging is at least as safe as staging by laparotomy with appropriate and similar oncological outcomes, but with the advantages of minimal access surgery. We therefore advocate the use of laparoscopy to achieve surgical staging for women with presumed early stage adnexal cancer.


Feasibility of ultrasonography in determining the diagnosis and treatment of perforated duodenal ulcer.
We diagnosed and treated perforated duodenal ulcers (PDUs) based on the results of ultrasonography (US). We obtained useful ultrasonographic findings regarding the diagnosis and treatment of PDU. We experienced 24 PDU cases over 6 years and 4 months (March 2002 to June 2008), and evaluated five useful ultrasonographic findings regarding PDU: (1) Two-way transmigration of liquid and air bubbles through the perforated duodenal wall, (2) hyperechoic band penetration out through the duodenal wall, (3) free air exiting the PDU, (4) fluid exiting the PDU, and (5) liver covering the PDU. Of the 24 cases, two-way transmigration was observed in 4 cases, hyperechoic band penetration was observed in 18 cases, and exiting free air and fluid was observed in all cases. In all patients with two-way transmigration of liquid and air bubbles, we could immediately diagnose PDU. For the PDU cases falling under categories 2, 3, and 4 above, upon analysis, a large majority provided useful ultrasonographic findings for diagnosing PDU. Of the 5 cases in which the liver did not cover the PDU at all, two-way transmigration of liquid and air bubbles was observed in 4 cases, and surgery was performed in all 5 cases. Of the 19 cases where the PDU was completely covered by the surrounding organs (the liver in 16 cases and fatty organs such as the round ligament or the omentum in 3 cases), nonsurgical treatment was selected in 18 cases. As a result, patients with PDUs covered by surrounding organs, mainly by the liver, received nonsurgical treatment, whereas those with noncovered PDUs underwent surgery. The findings of ultrasonography are useful for diagnosing and determining the treatment of PDU.


Quantification of manipulation forces needed for robot-assisted reduction of the ankle syndesmosis: an initial cadaveric study.
Manual surgical manipulation of the tibia and fibula is necessary to properly align and reduce the space in ankle fractures involving sprain of the distal tibiofibular syndesmosis. However, manual reduction is highly variable and can result in malreduction in about half of the cases. Therefore, we are developing an image-guided robotic assistant to improve reduction accuracy. The purpose of this study is to quantify the forces associated with reduction of the ankle syndesmosis to define the requirements for our robot design. Using a cadaveric specimen, we designed a fixture jig to fix the tibia securely on the operating table. We also designed a custom fibula grasping plate to which a force-torque measuring device is attached. The surgeon manually reduced the fibula utilizing this construct while translational and rotational forces along with displacement were being measured. This was first performed on an intact ankle without ligament injury and after the syndesmosis ligaments were cut. Six manipulation techniques were performed on the three principal directions of reduction at the cadaveric ankle. The results demonstrated the maximum force applied to the lateral direction to be 96.0 N with maximum displacement of 8.5 mm, applied to the anterior-posterior direction to be 71.6 N with maximum displacement of 10.7 mm, and the maximum torque applied to external-internal rotation to be 2.5 Nm with maximum rotation of 24.6°. The specific forces needed to perform the distal tibiofibular syndesmosis manipulation are not well understood. This study quantified these manipulation forces needed along with their displacement for accurate reduction of ankle syndesmosis. This is a necessary first step to help us define the design requirements of our robotic assistance from the aspects of forces and displacements.


Comparative benefits and limitations of 18F-FDG PET and CT-MRI in documented or suspected recurrent cervical cancer.
The purpose of this study was to assess the comparative benefits and limitations of (18)F-fluorodeoxyglucose (FDG) PET and CT-MRI in documented or suspected recurrence of cervical cancer after primary treatment. Three patient groups were enrolled. Group A patients had biopsy-documented recurrent or persistent cervical cancer. Group B patients had suspicion of recurrent tumour on CT-MRI without biopsy proof and were potentially curable. Group C patients were in complete remission after previous definitive treatment for histologically confirmed cervical carcinoma but had elevated serum squamous cell carcinoma antigen (tumour marker) levels despite negative CT-MRI. Clinical management decisions were recorded with CT-MRI alone and with additional FDG PET. Discordances and concordances between CT-MRI and FDG PET results were identified and related to final diagnosis as based on histopathology or follow-up. A total of 150 patients (ten regions per patient) were eligible for analysis, with 58 in group A, 52 in group B and 40 in group C. For the 149 discordant regions, 126 (84.6%) had final diagnoses. Of these final diagnoses, there was additional benefit from FDG PET over CT-MRI in 73.8% (93/126), with FDG PET correcting false negatives (FNs) on CT-MRI in 74.2% (69/93) and correcting false positives (FPs) on CT-MRI in 25.8% (24/93). Among lesions confirmed by FDG PET, 75.4% (52/69) were extra-pelvic. There was additional benefit of CT-MRI compared with FDG PET in 26.2% (33/126): in nine (27.3%) CT-MRI results were shown to be true positive (TP) whereas FDG PET yielded FN results, while in 24 (72.7%) CT-MRI corrected FP results on FDG PET. Among the nine FNs on FDG PET that were identified by CT-MRI, four were extra-pelvic. Among the FPs on FDG PET that were excluded by CT-MRI, 79.2% (19/24) were extra-pelvic. For recurrent cervical cancer, the benefits of FDG PET exceed those of CT-MRI owing to the ability of FDG PET to identify extra-pelvic metastases and its higher sensitivity and specificity.


Primary Ewing sarcoma of the lung: A systematic review of the recent literature.
Primary pulmonary Ewing sarcoma (PES) is a rare malignancy with only sporadic cases reported in the scientific literature. We performed a systematic review of the cases published in the last decade on PubMed, with the aim to describe the clinical, pathological, therapeutic, and prognostic data of PES. Forty-two articles reporting on 50 cases have been reviewed. Globally, 60 % of the patients were males, and the mean age at diagnosis was 30.5 years, with only a few cases diagnosed after 50 years of age. The most common clinical manifestations at diagnosis were dyspnea, cough and chest pain. The most common immunohistochemistry findings were staining for CD99 and (less frequently) for vimentin, and no staining for TTF-1, cytokeratin, desmin and S-100. ESWR1-FL1 translocation was tested in less than half of the cases. The disease was often locally advanced, treated generally with multidisciplinary treatment combining surgery, chemotherapy and radiation therapy. Among patients with follow-up data, approximately 40 % were dead at the time of publication, with the median survival being 11.5 months. Among those who were alive, only 8.3 % was free from disease at 48 months from diagnosis.


Fatty acid biosynthesis in Erlich cells. The mechanism of short term control by exogenous free fatty acids.
We have examined the mechanism by which extracellular free fatty acids regulate fatty acid biosynthesis in Ehrlich ascites tumor cells. De novo biosynthesis in intact cells was inhibited by stearate greater than oleate greater than palmitate greater than linoleate. The amount of citrate and long chain acyl-CoA in the cells was not changed appreciably by the addition of free fatty acids to the incubation medium, indicating than free fatty acids do not regulate fatty acid biosynthesis by changing the total intracellular content of these metabolites. By measuring the incorporation of labeled free fatty acids into acyl-CoA, however, it was determined that the fatty acid composition of the acyl-CoA poolwas changed dramatically to reflect the composition of the exogenous free fatty acids. The relative inhibitory effects of different free fatty acids appear to depend on the ability of their acyl-CoA derivatives to regulate acyl-CoA carboxylase activity. The acyl-CoA concentration needed to produce 50% inhibition of purified Ehrlich cell carboxylase was found to be 0.68 mum for stearoyl-CoA, 1.6 mum for oleoyl-CoA, 2.2 mum for palmitoyl-CoA, 23 mum for myristoyl-CoA, 30 mum for lauroyl-CoA, and 37 mum for linoleoyl-CoA. In contrast to their effects on de novo synthesis, all of the free fatty acids added except stearate stimulated chain elongation in intact cells. Microsomal chain elongation, the major system for elongation in Ehrlich cells, also was regulated by the composition of the cellular acyl-CoA pool. Lauroyl-CoA, myristoyl-CoA, and palmitoyl-CoA were good substrates for elongation by isolated microsomes; oleoyl-CoA, and linoleoyl-CoA were intermediate; and stearoyl-CoA was a very poor substrate. We conclude that free fatty acids regulate fatty acid biosynthesis by changing the composition of the cellular acyl-CoA pool. These changes control the rate of malonyl-CoA production and, because of the acyl-CoA substrate specificity of the microsomal elongation system, modulate the amount of malonyl-CoA used for chain elongation.


Cervical tuberculous lymphadenitis: Clinical profile and diagnostic modalities.
Tuberculosis is a major global health problem. Tuberculous lymphadenopathy is a most common form of extrapulmonary tuberculosis (EPTB), constitutes 35% of all cases of EPTB. Due to the paucibacillary nature of specimens, smear microscopy and culture offer low sensitivity. The aim of the present study was to find the clinicodemographic profiles and comparing the performance of Xpert MTB/RIF, conventional polymerase chain reaction (PCR), mycobacteria growth indicator tube (MGIT) 960, histopathological examination, and clinical follow-up of patients in diagnosing of smear-negative tuberculous lymphadenopathy. A total of 140 clinically suspected cervical tuberculous lymphadenitis cases were enrolled in this study. MGIT-960 culture, conventional PCR, and Xpert MTB/RIF were performed. Most of the patients presented with unilateral (87.14%), single (81.42%), matted (87.85%) lymph nodes, 3 cm-6 cm (52.14%), commonly in the right side (68.02%), and associated lung lesion was found in 12.86% of cases. The detection rates of Mycobacterium tuberculosis complex (MTBC) by Xpert MTB/RIF, conventional PCR, and MGIT were 25.71%, 20.71%, and 17.85%, respectively. Both the tests: Xpert MTB/RIF and PCR, PCR and MGIT, Xpert MTB/RIF and MGIT were positive in 15.71%, 15.71%, and 11.42% of cases, respectively. Most of the patients (74.1%) were cured with 6 months of antitubercular drugs. Clinicians often face the diagnostic dilemmas presented in the study. Individual modalities of the diagnosis are available, but all have drawbacks with varied sensitivity and specificity. Combining the available clinical, radiological, and microbiological modality to reach early diagnosis can go a long way to avoid misdiagnosis and unnecessary delay in treatment, especially in cases, without the pulmonary involvement and fulfilling the aim of National Tuberculosis Control Programme for EPTB cases.


Contrast enhancement with time in gliomas. Stereotactic computer tomography following contrast medium infusion.
Dynamic enhancement of astrocytomas has been investigated with CT following infusion of contrast medium. The areas of measurement corresponded with obtained stereotactic biopsies. The resulting types of enhancement are discussed in terms of a 3-compartment model. Great differences exist in the degree of enhancement of astrocytomas of grade I to II and those of grade III to IV. In the latter tumours a dynamic response appears to occur, distinctly different from that in infarctions.


Skeletal muscle basement membrane in maturity-onset diabetes in the young.
We have studied skeletal muscle capillary basement membrane width (CBMW) and intensity of skeletal muscle extracellular basement membrane staining for albumin and IgG in eight families with maturity-onset diabetes in the young (MODY). Ninety-two MODY patients were identified. Sixty-three of these patients, 33 relatives with nondiagnostic oral glucose tolerance studies, and 61 normoglycemic relatives were studied for glucose and insulin. Twenty-six of these MODY patients, 20 normoglycemic relatives, and 16 unrelated normal controls had skeletal muscle capillary morphologic studies. The muscle capillary basement membrane was significantly increased in MODY patients younger than 40 yr when compared with unrelated normal subjects and relatives of the same age (P less than 0.001). However, in these families, the CBMW of MODY patients showed no significant thickening with age (slope = 0.45, P less than 0.14), as expected and seen in the normal subjects and in the normoglycemic relatives of the patients (slope = 1.21, P less than 0.001). The slope derived from the linear regression of age and CBMW in MODY patients (0.45 +/- 0.29) was significantly less (P less than 0.05) than that of the nondiabetic subjects (1.21 +/- 0.19). The mean intensity of skeletal muscle extracellular basement membrane staining for albumin was higher in MODY patients (1.1 +/- 0.15) than in unrelated normal subjects (0.7 +/- 0.1, P less than 0.025) and normal MODY family members (0.6 +/- 0.08, P less than 0.01). The unexpected absence of basement membrane thickening with age in the MODY patients may explain the paucity of vascular complications that have been reported by some.(ABSTRACT TRUNCATED AT 250 WORDS)


Silicon photonic acoustic detector (SPADE) using a silicon nitride microring resonator.
Silicon photonics is an emerging platform for acoustic sensing, offering exceptional miniaturization and sensitivity. While efforts have focused on silicon-based resonators, silicon nitride resonators can potentially achieve higher Q-factors, further enhancing sensitivity. In this work, a 30 µm silicon nitride microring resonator was fabricated and coated with an elastomer to optimize acoustic sensitivity and signal fidelity. The resonator was characterized acoustically, and its capability for optoacoustic tomography was demonstrated. An acoustic bandwidth of 120 MHz and a noise-equivalent pressure of ∼ 7 mPa/Hz1/2 were demonstrated. The spatially dependent impulse response agreed with theoretical predictions, and spurious acoustic signals, such as reverberations and surface acoustic waves, had a marginal impact. High image fidelity optoacoustic tomography of a 20 µm knot was achieved, confirming the detector's imaging capabilities. The results show that silicon nitride offers low signal distortion and high-resolution optoacoustic imaging, proving its versatility for acoustic imaging applications.


Hollow mesoporous silica as a high drug loading carrier for regulation insoluble drug release.
The purpose of this study was to develop a high drug loading hollow mesoporous silica nanoparticles (HMS) and apply for regulation insoluble drug release. HMS was synthesized using hard template phenolic resin nanoparticles with the aid of cetyltrimethyl ammonium bromide (CTAB), which was simple and inexpensive. To compare the difference between normal mesoporous silica (NMS) and hollow mesoporous silica in drug loading efficiency, drug release behavior and solid state, NMS was also prepared by soft template method. Transmission electron microscopy (TEM), specific surface area analysis, FT-IR and zeta potential were employed to characterize the morphology structure and physicochemical property of these carriers. The insoluble drugs, carvedilol and fenofibrate(Car and Fen), were chosen as the model drug to be loaded into HMS and NMS. We also chose methylene blue (MB) as a basic dye to estimate the adsorption ability of these carriers from macroscopic and microscopic view, and the drug-loaded carriers were systematically studied by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and UV-vis spectrophotometry. What' more, the in vivo process of HMS was also study by confocal microscopy and in vivo fluorescence imaging. In order to confirm the gastrointestinal safety of HMS, the pathological examination of stomach and intestine also be evaluated. HMS allowed a higher drug loading than NMS and exhibited a relative sustained release curve, while NMS was immediate-release. And the effect of preventing drugs crystallization was weaker than NMS. As for in vivo process, HMS was cleared relatively rapidly from the mouse gastrointestinal and barely uptake by intestinal epithelial cell in this study due to its large particle size. And the damage of HMS to gastrointestinal could be ignored. This study provided a simple method to obtain high drug loading and regulation insoluble drug release, expanded the application of inorganic carriers in drug delivery system and pharmaceutic adjuvant.


Cryo-EM and cryo-ET of the spike, virion, and antibody neutralization of SARS-CoV-2 and VOCs.
Since the outbreak of the COVID-19 pandemic, cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET) have been demonstrated to be powerful and efficient tools in structural studies of distinct conformational states of the trimeric spike protein of SARS-CoV-2 and the VOCs as well as the intact virion. Cryo-EM has also contributed greatly to revealing the molecular basis of receptor recognition and antibody neutralization of the S trimer. Additionally, it has provided structural insights into the enhanced transformation and immune evasion of the VOCs, thus facilitating antiviral antibody and drug discovery. In this review, we summarize the contributions of cryo-EM and cryo-ET in revealing the structures of SARS-CoV-2 S trimer and intact virion and the mechanisms of receptor binding and antibody neutralization. We also highlight their prospective utilities in the development of vaccines and future therapeutics against emerging SARS-CoV-2 variants and other epidemic viruses.