Raking of data from a large Australian cohort study improves generalisability of estimates of prevalence of health and behaviour characteristics and cancer incidence.
Health surveys are commonly somewhat non-representative of their target population, potentially limiting the generalisability of prevalence estimates for health/behaviour characteristics and disease to the population. To reduce bias, weighting methods have been developed, though few studies have validated weighted survey estimates against generally accepted high-quality independent population benchmark estimates. We applied post-stratification and raking methods to the Australian 45 and Up Study using Census data and compared the resulting prevalence of characteristics to accepted population benchmark estimates and separately, the incidence rates of lung, colorectal, breast and prostate cancer to whole-of-population estimates using Standardised Incidence Ratios (SIRs). The differences between 45 and Up Study and population benchmark estimates narrowed following sufficiently-informed raking, e.g. 13.6% unweighted prevalence of self-reported fair/poor overall health, compared to 17.0% after raking and 17.9% from a population benchmark estimate. Raking also improved generalisability of cancer incidence estimates. For example, unweighted 45 and Up Study versus whole-of-population SIRs were 0.700 (95%CI:0.574-0.848) for male lung cancer and 1.098 (95%CI:1.002-1.204) for prostate cancer, while estimated SIRs after sufficiently-informed raking were 0.828 (95%CI:0.684-0.998) and 1.019 (95%CI:0.926-1.121), respectively. Raking may be a useful tool for improving the generalisability of exposure prevalence and disease incidence from surveys to the population.


Enzyme-linked immunosorbent determination of autoantibodies to zona pellucida as a possible cause of infertility in women.
An enzyme-linked immunosorbent assay (ELISA) for determination of antibodies against the zona pellucida was developed and compared with the already available indirect immunofluorescence (IIF) technique. Sera from 100 women with explained and unexplained infertility were screened for the presence of autoantibodies to the zona pellucida by ELISA and IIF techniques. Porcine/goat zonae immobilized on activated microtitre plates or solubilized zona pellucida antigens adsorbed on poly-L-lysine-coated microtitre plates were used as a solid phase in an ELISA. Assay of anti-zona pellucida antibodies in xenogeneic and allogeneic sera was performed by incubation of test samples with the solid phase against human serum supplied by WHO as a reference positive control, followed by incubation with staphylococcal protein A conjugated to horseradish peroxidase. The ELISA was effectively used to screen the production of monoclonal antibodies from mouse myeloma X mouse splenocyte hybridomas. The sensitivity of the ELISA was more than 2500-fold greater than that of the IIF technique. Significantly high titres of autoantibodies to zona pellucida were found in patients with unexplained infertility as compared with patients with a known cause of infertility, and their normal counterparts.


Hemodynamic changes during balloon-occluded transarterial chemoembolization (B-TACE) of hepatocellular carcinoma observed by contrast-enhanced ultrasound.
Balloon-occluded transarterial chemoembolization (B-TACE) is able to achieve denser accumulation of Lipiodol emulsion (LE) in hepatocellular carcinoma (HCC) than conventional TACE. However, to maximize the therapeutic effect of B-TACE, it is imperative to understand the hemodynamic changes that occur during arterial occlusion. We here present two patients with HCC in whom the hemodynamic changes during arterial occlusion were depicted and evaluated by contrast-enhanced ultrasound (CEUS). Arterial flow beyond the catheter tip was observed by CEUS even after balloon occlusion. In one patient, a reduction in arterial blood flow in the HCC was observed by CEUS during balloon occlusion of the target area for embolization. After B-TACE, dense LE accumulation in the HCC nodule was confirmed by flat-panel detector CT, indicating an excellent therapeutic effect. In the other patient, no changes in arterial blood flow in the HCC nodule were observed by CEUS during balloon occlusion of the target area for embolization. After B-TACE, intermediate LE accumulation in the HCC nodule was confirmed by flat-panel detector CT, indicating an incomplete therapeutic effect. The findings obtained in the two patients presented here suggest that B-TACE can be performed more effectively and reliably by monitoring blood flow using CEUS.


Cytokine profiles, CTL response and T cell frequencies in the peripheral blood of acute patients and individuals recovered from hepatitis E infection.
Hepatitis E is a major public health problem in the developing countries. Pathogenesis of hepatitis E virus (HEV) infection is poorly understood. This case-control study included 124 Hepatitis E patients (46 acute and 78 recovered), 9 with prior exposure to HEV and 71 anti-HEV negative healthy controls. HEV induced CTL response by Elispot, cytokines/chemokines quantitation by Milliplex assay and peripheral CD4+ & CD8+ T cell frequencies by flow cytometry were assessed. Among the patient categories, HEV specific IFN-γ responses as recorded by Elispot were comparable. Comparisons of cytokines/chemokines revealed significantly high levels of IL-1α and sIL-2Rα during acute phase. Circulating peripheral CD4/CD8+ T-cell subsets in acute and recovered individuals were comparable compared to controls, while among patient categories CD8+T cell subset was significantly higher in recovered individuals. Our findings suggest that IL-1α and sIL-2Rα play a role in the pathogenesis of acute Hepatitis E infection. Lack of robust HEV ORF2-specific CTL response in the peripheral blood of HEV infected patients during the acute and recovered phases of the disease may be associated with involvement of innate immune cells/localization of the immune events at the site of infection.


Fatal hepatic failure after jejunoileal bypass: clinical and laboratory evidence of prognostic significance.
Experience with 393 patients undergoing elective jejunoileal bypass procedures is presented with attention directed to the complication of fatal hepatic failure. A retrospective analysis of pre- and postoperative liver function studies is undertaken to identify patients who may develop postoperative fatal hepatic failure.


A case of shaken baby syndrome after discharge from the newborn intensive care unit.
Preterm infants may be at higher risk of physical abuse after hospital discharge. Nonaccidental or inflicted head neurotrauma is the most common cause of mortality and morbidity in physical-abuse cases, and shaken baby syndrome (SBS) is the most common form of abuse. In the majority of the cases, parents who shake their infant do not intend to harm the infant. This article presents a report of a former preterm infant who presented to the pediatrician's office with a maternal report of an accidental fall. Shaken baby syndrome was suspected based on bilateral subdural hemorrhages of varying ages, which were inconsistent with the history provided. The differential diagnosis and systematic clinical evaluation for SBS are provided, and medical and nursing management is discussed. Patient care, advocacy, and mandatory reporting are reviewed. The newborn intensive care unit caregivers' role in preventing SBS in this high-risk population, including specific parent teaching and anticipatory guidance, is reviewed with an emphasis on teaching all caregivers about the dangers of shaking an infant.


Avian adipose lipoprotein lipase: cDNA sequence and reciprocal regulation of mRNA levels in adipose and heart.
cDNA clones for chicken adipose lipoprotein lipase were isolated from an expression library in lambda gt11 by antibody screening and characterized by hybridization selection and nucleotide sequencing. Based on the cDNA sequence and on N-terminal sequence analysis of the purified enzyme, chicken adipose lipoprotein lipase is a mature protein of 465 amino acids with a signal peptide of 19 or 25 amino acids, depending on which of two methionine residues is used for translation initiation. The predicted amino-acid sequence was found to be 73-77% identical to the four known mammalian adipose lipoprotein lipase sequences, with conservation of position of cysteine residues and putative functional domains, and number of potential N-glycosylation sites. Chicken lipoprotein lipase differs from mammalian lipoprotein lipases with respect to the position of one N-glycosylation site and the presence of an additional 15-17 C-terminal amino acids. 32P-labeled cDNA clones hybridized to mRNA species of 3.7 and 4.0 kb in Northern blots of heart and adipose, but not of liver RNA. In chickens that were fasted for 48 h and then refed, lipoprotein lipase mRNA levels in adipose increased to a maximal level of 350% that of controls at 10 h, whereas heart lipoprotein lipase mRNA levels fell to 40% of controls at 14 h. Concomitantly, no changes in total RNA were observed. Thus, avian lipoprotein lipase is subject to reciprocal pretranslational regulation in adipose and heart.


Role of computed tomography in diverticulitis.
Fourteen patients with diverticulitis who were clinically believed to require radiologic investigation form the basis of this report. An inflammatory mass (n = 10) or abscess (n = 2) were reliable findings on computed tomography. Other signs encountered were abnormal density of pericolic fat, thickening of colonic wall, and narrowing of the lumen of the colonic wall. Colovesical fistulas, all of which were suspected clinically, occurred in three patients. Computed tomography should be performed with administration of rectal contrast medium to demonstrate the origin of inflammation from the colon, assess pericolic extent, and confirm colovesical fistula.


Effect of aminoguanidine on the generation of superoxide anion and nitric oxide by peripheral blood granulocytes of rats with streptozotocin-induced diabetes.
The effect of aminoguanidine (AG) on the production of superoxide anion O2*- and nitric oxide (NO) by peripheral blood granulocytes of rats with streptozotocin-induced diabetes was studied. Induction of diabetes resulted in an increase of O2*-. Generation by both unstimulated and opsonized zymosan-stimulated granulocytes was maximal after 6 weeks and lower after 12 weeks. Treatment with aminoguanidine (1 g/l drinking water) decreased O2*- generation after 6 weeks but not after 12 weeks. NO production by both unstimulated and opsonized zymosan-stimulated granulocytes was elevated in diabetic rats to a comparable extent after 6 and 12 weeks. AG attenuated this increased NO production. These results point to the beneficial effect of AG on oxidative stress in experimental diabetes and suggest an antioxidant effect of AG.


Migration of sporozoites and merogony of Eimeria coecicola in gut-associated lymphoid tissue.
The invasive phase of Eimeria coecicola was studied during the first 80 h postinoculation (p.i.). Using a method that synchronized the life cycle, sporozoites were observed in the duodenum and the jejunum until 32 h p.i. They were seen first in the villous epithelial cells or in host cells resembling intraepithelial lymphocytes (IEL). Later they were observed in IEL in the lamina propria. After 48 h p.i., no coccidian stage was identifiable in the mucosa of the small intestine but sporozoites appeared in the lymphoid cells of lymphatic follicles of the gut-associated lymphoid tissue (vermiform appendix, sacculus rotundus, and Peyer's patches). The first merogony was observed 64 h p.i. in these lymphoid cells and in membranous epithelial cells (M-cells) but was never seen in the epithelium itself. Morphologically there were two types of meronts, depending on the host cell type, but in both cases the merozoites contained a refractile body and resembled sporozoites. The first meronts of the second generation were observed 80 h p.i. in the villous epithelial cells of the domes of the follicles of the gut-associated lymphoid tissue, where the further development of this Eimeria takes place. This pattern of invasion strongly suggests that sporozoites take an exclusively extraintestinal route to reach the target cells. Moreover, to our knowledge this is the first description of an eimerian merogony that does not take place in epithelial cells.


Fine mapping of the sequences in domain 5 of high molecular weight kininogen (HK) interacting with heparin and zinc.
We previously localized the heparin binding region on high molecular weight kininogen to domain 5 (D5) by quantifying the binding using surface plasmon resonance of D5 fused at its N-terminal to glutathione-S-transferase. We further examined GST-(H475-S626) which at 100 nm was previously shown to be ineffective in reversing the heparin acceleration of antithrombin inhibition of thrombin. However, we now show that at a concentration of 400 nm, complete reversal of accelerated inhibition occurred. To characterize the interacting sequences on D5, four peptides representing surface loops of a molecular model were synthesized. Peptides H475-H485 and G440-G455, rich in histidine and low in lysine, showed weak or no detectable binding in the absence of Zn++, but tighter binding in the presence of Zn++. H483-K497 containing three histidines and six lysines showed tight binding without Zn++, and increased in avidity with Zn++. In contrast, G486-K502, low in histidine and high in lysine, showed tight binding (KD = 0.8 microm) in the absence and presence of Zn++. Both H483-K497 and G486-K502 were effective in neutralizing the accelerated inhibition by heparin of thrombin by antithrombin in the absence of Zn++. Therefore, a set of lysine residues in the sequence of K487-K502 is responsible for Zn++-independent binding of heparin. Further, a group of histidine residues in sequence range of H475-H485 contributes to Zn++-dependent binding of heparin to HK-D5.


Leader-follower controllability of signed networks.
This study addresses leader-follower controllability of signed multi-agent networks with fixed and switching interactions (topologies), respectively, where weighted edges between agents may be positive or negative. In other words, there exist cooperative interactions (corresponding to positive edges) and antagonistic interactions (corresponding to negative edges) between agents in the multi-agent networks depicted by signed graphs. The goal of this study is to find the criteria of controllability for signed multi-agent networks, that is, how exactly do cooperation and antagonism affect controllability? It is proven that the followers of multi-agent networks under structurally balanced conditions can be controlled to the desired states if the leaders are chosen from the same partitioned subset. In addition, a signed multi-agent network with simultaneously structurally balanced conditions can be switching controllable even though each subsystem is uncontrollable. The leaders' selection is also discussed.


Extraction of a well fixed but fractured ceramic acetabular liner.
Ceramic fractures have been reported to occur in hip replacements, but the techniques used to extract a well fixed but fractured component are not commonly described. We present a case of ceramic liner fracture and validate a modification of a previously reported extraction technique that allowed us to save the acetabular cup and insert a polyethylene liner. With an increasing trend in ceramic bearing usage, it is likely that the number of ceramic liner fractures will increase and therefore knowledge of successful extraction techniques will be desirable.


Effects of triclosan on the RedoximiRs/Sirtuin/Nrf2/ARE signaling pathway in mosquitofish (Gambusia affinis).
Triclosan (TCS) has been widely used in daily life for its broad-spectrum antibacterial property and subsequently detected frequently in aquatic waterborne. Environmental relevant concentrations of TCS in water (ng-μg/L) may pose potential unexpected impact on non-target aquatic organisms. In the present work, we investigated the transcriptional responses of Nrf2 as well as its downstream genes, sirtuins and redox-sensitive microRNAs (RedoximiRs) in livers of the small freshwater fish mosquitofish (Gambusia affinis) which were exposed to environmental relevant concentrations of TCS (0.05 μg/L, 0.5 μg/L and 5 μg/L for 24 h and 168 h). Results showed there were similar up-regulations in Nrf2 and its target genes (e. g. NQO1, CAT and SOD) at transcriptional, enzymatic and protein levels, reflecting oxidative stress of TCS to mosquitofish. Meanwhile, up-regulations of Sirt1, Sirt2 and down-regulations of miR-34b, miR-200b-5p and miR-21 could modulate antioxidant system via the Nrf2/ARE signaling pathway by the post-transcriptional regulations. Some oxidative stress-related biomarkers displayed in concentration-dependent manners (e. g. NQO1 mRNA, CAT mRNA) and/or time-dependent manners (e. g. GSH contents). This study indicated that the RedoximiRs/Sirtuin/Nrf2/ARE signaling pathway played a crucial role in mosquitofish exposed to TCS, and there might be potentially profound effects for TCS on the aquatic ecological safety.


Progression-free survival as surrogate endpoint of overall survival in esophageal squamous cell carcinoma: a real-world data and literature-based analysis.
The surrogacy of progression-free survival (PFS) for overall survival (OS) in esophageal squamous cell carcinoma (ESCC) remains unelucidated. This study aimed to determine the validity of PFS as a surrogate endpoint for OS in ESCC patients treated with definitive radiotherapy or definitive chemoradiotherapy (dRT/dCRT), as well as characterize the prognostic factors and survival of such patients. A total of 3662 patients from 10 cancer centers were enrolled. One-, 2-, and 3-year PFS (PFS12, PFS24, and PSF36, respectively) were used as time points for analysis. At each time point, ESCC-specific mortality and OS were characterized using competing risk and conditional survival models, while correlation between PFS and OS was evaluated by linear regression. At PFS12, PFS24, and PFS36, a progressive decrease in 5-year ESCC-specific mortality (35.2%-13.4%) and increase in 5-year OS (46.6%-62.9%) were observed. Regardless, the OS of patients remained markedly lower than those of the age- and sex-matched Chinese general population. TNM stage remained a significant prognostic factor at PFS36. Strong correlation was found between 3-year PFS and 5-year OS, which was further externally validated. Three-year PFS may act as a potential surrogate endpoint for 5-year OS. TNM stage was considered a significant prognostic factor for OS, and may represent the optimal prognostic tool to guide clinical decision-making and post-treatment follow-up.


[To be (a girl) or not to be! Or the sex of the angels? Problems in individuation (and identification) in a 3-year-old child. Case report, theoretical comments, treatment].
During a lengthy hospitalization in a pedopsychiatric department, with an intermediate several-week period at home, a child seen at the age of three with severe disorders of relationships and identity was able to progress significantly and to improve organization of personality. The authors report this case and show that this child's problems are largely due to the distortion of family relationships and personal identification problems of the two young parents who were unable to assume freely their own parental role for this child.


Providing English and native language quotes in qualitative research: A call to action.
When publishing qualitative research in international journals, researchers studying non-English-speaking participants provide quotes in English language. This is an issue of increasing concern given the need to be rigorous to represent a diversity of participants within their context, beyond how language (alone) situates them. To argue for providing English and native language quotes in qualitative research reports. Discussion. This paper is based on the literature on use of quotes and translation in qualitative research and authors' experiences of publishing qualitative research. Provision of native and English language quotes may allow for greater transparency of findings, thereby reflecting that the researchers adequately captured the socially and culturally dependent experiences of participants. Presentation of findings with eloquent quotes serves as the gateway into the sociocultural experiences of individuals. We argued against the norm of providing translated quotes in qualitative reports and build a case for the provision of native as well as English language quotes to promote cross-cultural understanding.


Peripheral vascular disease as remote ischemic preconditioning, for acute stroke.
Remote ischemic preconditioning (RIPC) is a powerful endogenous mechanism whereby a brief period of ischemia is capable of protecting remote tissues from subsequent ischemic insult. While this phenomenon has been extensively studied in the heart and brain in animal models, little work has been done to explore the effects of RIPC in human patients with acute cerebral ischemia. This study investigates whether chronic peripheral hypoperfusion, in the form of pre-existing arterial peripheral vascular disease (PVD) that has not been surgically treated, is capable of inducing neuroprotective effects for acute ischemic stroke. Individuals with PVD who had not undergone prior surgical treatment were identified from a registry of stroke patients. A control group within the same database was identified by matching patient's demographics and risk factors. The two groups were compared in terms of outcome by NIH Stroke Scale (NIHSS), modified Rankin scale (mRS), mortality, and volume of infarcted tissue at presentation and at discharge. The matching algorithm identified 26 pairs of PVD-control patients (9 pairs were female and 17 pairs were male). Age range was 20-93 years (mean 73). The PVD group was found to have significantly lower NIHSS scores at admission (NIHSS≤4: PVD 47.1%, control 4.35%, p<0.003), significantly more favorable outcomes at discharge (mRS≤2: PVD 30.8%, control 3.84%, p<0.012), and a significantly lower mortality rate (PVD 26.9%, control 57.7%, p=0.024). Mean acute stroke volume at admission and at discharge were significantly lower for the PVD group (admission: PVD 39.6 mL, control 148.3 mL, p<0.005 and discharge: PVD 111.7 mL, control 275 mL, p<0.001). Chronic limb hypoperfusion induced by PVD can potentially produce a neuroprotective effect in acute ischemic stroke. This effect resembles the neuroprotection induced by RIPC in preclinical models.


Deciphering microbiomes in anaerobic reactors with superior trichloroethylene dechlorination performance at low pH conditions.
Different pH conditions have been demonstrated to affect the activities of dechlorinating populations participating in the successive dechlorination of trichloroethylene to ethylene. However, the mechanism of the effect of pH conditions on the assembly of dechlorinating populations and their relations to the structure, function, and dynamics of the microbiome are unclear. In this study, we evaluated the effects of pH on microbiomes assembled in anaerobic trichloroethylene-dechlorinating reactors under neutral (pH 7.2), acidic (pH 6.2), and alkaline (pH 8.2) conditions. The results revealed that among the reactors, the acidic reactor had the highest efficiency for dechlorination without accumulation of dechlorinated metabolites, even at high loading rates. The results of high-throughput sequencing of the 16S rRNA gene indicated that the microbiomes in the 3 reactors underwent varied dynamic succession. The acidic reactor harbored a higher degree of complex microbes, dechlorinator diversity, and abundance of the Victoria subgroup of Dehalococcoides (1.2 ± 0.1 × 106 cell/mL), which were approximately 10-102-fold higher than those at neutral and alkaline conditions. The pH settings altered species-species connectivity and complexity of microbial interaction networks, with more commensal interactions in the dechlorinators of the acidic reactor. As predicted, abundances of several functional gene categories were in strong linearity with pH values, and the microbiome possessed significantly more abundant functions in the acidic reactor (P < 0.001), such as potentially stimulating hydrogen production, cobalamin synthesis, cobalt transport, transport and metabolism of amino acids and secondary metabolites, cell motility, and transcription. All results of microbiomic analyses consistently revealed the observed superior dechlorination process and suggested an association of the reductive dechlorination process with the pH-dependent microbiome. The results of this study provide a new insight into the trichloroethylene dechlorination with regards to pH, and they will be useful for improving bioremediation and management of trichloroethylene-contaminated sites.


Prevention of stress-induced analgesia by substance P.
It has been shown that a variety of stressful procedures, such as immobilization and footshock, can induce a significant degree of analgesia in mice. In addition, it has been shown that for some, but not all, stressful treatments, the analgesic effect is mediated via endogenous opioids. This report describes the effects of substance P, administered systemically, on both opioid-mediated immobilization-induced analgesia and non-opioid footshock-induced analgesia. Substance P completely blocked the opioid-mediated form of stress-induced analgesia while having no effect on the non-opioid form. Exogenous substance P appears to interact with endogenous opioid pain-suppressing systems.


Integrative cancer care in a certified Cancer Centre of a German Anthroposophic hospital.
The concept of integrative oncology (IO) comprising guideline-oriented standard and add-on complementary medicine has gained growing importance. The Anthroposophic-integrative Cancer Centre (CC) at the hospital Gemeinschaftskrankenhaus (GKH) in Berlin has been implementing IO concepts during recent years. Furthermore, it is a certified CC and has been annually audited by national cancer authorities since 2012. The objective of the present study was to evaluate IO concepts of the certified CC GKH. Clinical, demographic, integrative treatment and follow-up data were analyzed between 2011 and 2016. In addition, CC GKH quality measures were compared with those of nationwide benchmarking CCs. Between 2011 and 2016, 2.382 primary cancer patients, median age 66 years, were treated at the CC GKH. 70.1% of the patients showed either Union for International Cancer Control (UICC) stage 0, I, II or III and 25.6% were in UICC stage IV. IO therapies included surgery (64.4% of patients), radiation (41.2%), and application of cytostatic drugs (53.9%), add-on mistletoe therapy (30.5%), and non-pharmacological interventions (87.3%). Regarding psycho-oncological support and quota of patient's enrollment in studies the CC GKH performs above nationwide benchmarks. Research outcomes including safety issues, clinical impact as well as patient's health-related quality of life are continuously evaluated and integrated into hospital's decision-management. This analysis reveals that IO concepts are applied to a high proportion of male and female primary cancer patients of all age groups, indicating a successful implementation at the certified CC GKH. Ongoing clinical evaluations have been initiated and cost-effectiveness comparisons are under analyses.


How to achieve better effect of peer support among adults with type 2 diabetes: A meta-analysis of randomized clinical trials.
To study the effects of peer support on glycemic control and examine effects of different providers and types of support, intervention duration and effect duration.


Analysis of causes of failure of medical treatment in patients undergoing surgery for benign prostate enlargement.
To analyse causes of failure of medical management in benign prostate enlargement (BPE) in patients who undergo surgery following medical treatment and to elucidate parameters which warrant for early surgical treatment. Records of 747 patients who underwent surgery for BPE were reviewed for prostate volume, median lobe enlargement, post void residual urine, duration and type of medical treatment given for BPE. We used univariate and multivariate analysis to find out significant parameters for medical treatment failure. A total of 601 patients (80.45%) received medical treatment for their lower urinary tract symptoms (LUTS), for a duration ranging between 3 months and 2 years. Statistically significant difference was found between age, prostate volume, intravesical projection, PSA and acute urinary retention with failure of medical treatment. BPE patients with failure to respond with medical management within 3-6 months and/or associated with large size prostate, intravesical projection and raised serum PSA should better be offered surgical treatment.


Low level lead and inhibition of erythrocyte pyrimidine nucleotidase.
Pyrimidine 5'-nucleotidase (P5N, EC 220.127.116.11) appears to be a sensitive index of exposure to low level lead. In 21 children 2 to 5 years old with blood leads of 7 to 80 micrograms/dl there was a negative linear correlation of blood lead and red cell P5N: r = -0.60 (P less than 0.01), Y = -0.11X + 12.3. In rats, the enzyme assay was quantitatively similar to that of the human. A treatment group of 12 rats received lead acetate, 36 mg/kg/day, of lead as 0.17 M lead acetate for 24 days. The blood lead of treated rats increased from the control value of 8.3 +/- 1.3 to 36.0 +/- 0.5 on day 24; P5N decreased from 18.3 +/- 0.8 units to 9.0 +/- 1.0 and was below control values at a blood lead of 25. There was a significant negative linear correlation of blood lead and P5N: r = -0.85; n = 17; P less than 0.001; Y = 0.34X + 20.9 that was independent of the correlationship with the reticulocytes. At these levels of blood lead and P5N there was no significant change in the hexokinase, hemoglobin or red cell count and no evidence of stippling.


Analgesic and other pharmacological activities of an enkephalin analogue, syndyphalin (SD)-25.
The pharmacological actions of Tyr-D-Met(O)-Gly-MePheol (syndyphalin (SD)-25) were compared with those of morphine after systemic administration. The analgesic potency of SD-25 was about 4 times that of morphine when administered s.c. to rats. SD-25 did not exhibit any narcotic antagonist activity. Subcutaneous administration of SD-25 produced a dose-dependent suppression of morphine withdrawal signs in morphine-dependent rats, typical morphine-like jumping in the mouse jumping test, and an increase in spontaneous locomotor activity in mice. These activities were 2-5 times those of morphine. In the anaesthetized dog, intravenous administration of SD-25 produced a 100-1000 times stronger increase in the amplitude of contractions of the jejunum than did morphine, a weaker depression in respiration than morphine, and a slight increase in blood pressure. These effects were reversed by naloxone. These results indicate that SD-25 possesses potent central nervous system actions closely similar to those of morphine, but its effect on blood pressure and respiration was weaker than that of morphine.


Iridocyclectomy for melanomas of the ciliary body: a follow-up study of pathology and surgical morbidity.
With respect to the effect of surgical treatment upon the eye and the subsequent tumor behavior, 107 cases of ciliary body melanoma treated by iridocyclectomy were studied. Surgically induced complications are discussed; 6% of the patients operated on culminated in enucleation, and 42% of the patients had a final postoperative visual acuity of 20/40 or better. Pathologically, most of the cases were spindle cell A or B; a few were mixed or epithelioid type. Histologic evidence of incomplete excision did not regularly predict recurrence in the interval of observation. Cell type is the primary prognostic feature. Local complications such as recurrence of tumor, or the rare metastasis occur early.


Corrigendum: Pharmacokinetics and bioequivalence study of esomeprazole magnesium enteric-coated tablets 20 mg in healthy Chinese subjects under fasting and fed conditions.
[This corrects the article DOI: 10.3389/fphar.2023.1169103.].


A precise microalgae farming for CO2 sequestration: A critical review and perspectives.
Microalgae are great candidates for CO2 sequestration and sustainable production of food, feed, fuels and biochemicals. Light intensity, temperature, carbon supply, and cell physiological state are key factors of photosynthesis, and efficient phototrophic production of microalgal biomass occurs only when all these factors are in their optimal range simultaneously. However, this synergistic state is often not achievable due to the ever-changing environmental factors such as sunlight and temperature, which results in serious waste of sunlight energy and other resources, ultimately leading to high production costs. Most control strategies developed thus far in the bioengineering field actually aim to improve heterotrophic processes, but phototrophic processes face a completely different problem. Hence, an alternative control strategy needs to be developed, and precise microalgal cultivation is a promising strategy in which the production resources are precisely supplied according to the dynamic changes in key factors such as sunlight and temperature. In this work, the development and recent progress of precise microalgal phototrophic cultivation are reviewed. The key environmental and cultivation factors and their dynamic effects on microalgal cultivation are analyzed, including microalgal growth, cultivation costs and energy inputs. Future research for the development of more precise microalgae farming is discussed. This study provides new insight into developing cost-effective and efficient microalgae farming for CO2 sequestration.


External validation of the ProACS score for risk stratification of patients with acute coronary syndromes.
The ProACS risk score is an early and simple risk stratification score developed for all-cause in-hospital mortality in acute coronary syndromes (ACS) from a Portuguese nationwide ACS registry. Our center only recently participated in the registry and was not included in the cohort used for developing the score. Our objective was to perform an external validation of this risk score for short- and long-term follow-up. Consecutive patients admitted to our center with ACS were included. Demographic and admission characteristics, as well as treatment and outcome data were collected. The ProACS risk score variables are age (≥72 years), systolic blood pressure (≤116 mmHg), Killip class (2/3 or 4) and ST-segment elevation. We calculated ProACS, Global Registry of Acute Coronary Events (GRACE) and Canada Acute Coronary Syndrome risk score (C-ACS) risk scores for each patient. A total of 3170 patients were included, with a mean age of 64±13 years, 62% with ST-segment elevation myocardial infarction. All-cause in-hospital mortality was 5.7% and 10.3% at one-year follow-up. The ProACS risk score showed good discriminative ability for all considered outcomes (area under the receiver operating characteristic curve >0.75) and a good fit, similar to C-ACS, but lower than the GRACE risk score and slightly lower than in the original development cohort. The ProACS risk score provided good differentiation between patients at low, intermediate and high mortality risk in both short- and long-term follow-up (p<0.001 for all comparisons). The ProACS score is valid in external cohorts for risk stratification for ACS. It can be applied very early, at the first medical contact, but should subsequently be complemented by the GRACE risk score.


Usefulness of a pericardial friction rub after thrombolytic therapy during acute myocardial infarction in predicting amount of myocardial damage. The TAMI Study Group.
To evaluate the clinical incidence and outcomes of patients with pericarditis after thrombolytic therapy, 810 patients were prospectively studied during acute myocardial infarction (AMI). Pericarditis was defined as the presence of a pericardial friction rub during the hospital course. Only 5% of patients developed a rub during AMI, a low percent compared with that in the prethrombolytic era. A pericardial friction rub more often occurred in the setting of an anterior wall AMI. Patients with, compared to those without, a pericardial friction rub had lower ejection fractions (45 vs 51%, p = 0.002); worse regional left ventricular function (-3.2 vs 2.7, standard deviation per chord); higher in-hospital mortality (15 vs 6%, p = 0.056); a higher frequency of power failure (83 vs 57%); a higher frequency of anterior wall location of the AMI (53% of cases, p = 0.002); and a higher frequency of 3-vessel disease. Therefore, although the frequency of a pericardial friction rub was low (5%) compared with that in the prethrombolytic era, its occurrence denotes more extensive myocardial damage with a worse clinical outcome. Perhaps with successful reperfusion of the infarct-related vessel, transmural myocardial necrosis is prevented and with it the development of pericarditis. Cardiac tamponade did not occur clinically in any patient who developed a pericardial friction rub.


Potential chemotherapeutic activity of 4-iodo-3-nitrobenzamide. Metabolic reduction to the 3-nitroso derivative and induction of cell death in tumor cells in culture.
A C-nitroso prodrug, 4-iodo-3-nitrobenzamide, was synthesized, and its action on a variety of tumor cells of human and animal origin tested. This prodrug was reduced transiently by tumor cells to 4-iodo-3-nitrosobenzamide at a very low rate, which was, however, sufficient to kill tumor cells. The final reduction product was 4-iodo-3-aminobenzamide, and no intermediates accumulated. No toxicity could be observed in hamsters even at 200 mg/kg, given i.p. daily for 7 days. The chemical reactivity of both 4-iodo-3-nitrosobenzamide and its noniodinated homolog with reduced ascorbate yielded the hydroxylamines. With glutathione, 4-iodo-3-aminobenzamide was formed, suggesting glutathione sulfinic acid formation. Confirming earlier studies, 4-iodo-3-nitrosobenzamide inactivated poly(ADP-ribose) polymerase by zinc ejection from the first zinc finger of this nuclear protein. The iodinated nitroso compound was more effective than its iodine-free analog. Selective tumoricidal action appeared to correlate with the reduction of the nitro group to nitroso in tumor cells, and with the previously described subsequent induction of tumor apoptosis by the C-nitroso intermediate. These processes were accelerated by buthionine sulfoximine, which diminishes cellular GSH.


Aortic Valve Repair Results in Better 1-Year Survival Than Replacement: Results From German Aortic Valve Registry.
Aortic valve (AV) repair is an evolving surgical strategy in the treatment of nonelderly adults with aortic regurgitation. We aimed to determine the 1-year outcome after AV repair vs surgical AV replacement (sAVR) using real-world data from the German Aortic Valve Registry. A total of 8076 aortic regurgitation patients (mean age, 59.1 ± 15.0 years; 76% men; mean The Society of Thoracic Surgeons score, 1.3 ± 1.1), who underwent AV surgical procedures between 2011 and 2015, were identified from German Aortic Valve Registry. The AV was repaired in 2327 patients (29%), and the remaining 5749 patients (71%) underwent sAVR. A weighted propensity score model, including the variables of age, sex, and The Society of Thoracic Surgeons score, was used to correct for baseline differences between AV repair and sAVR cohorts. The primary end point was 1-year survival after AV repair vs sAVR. Secondary end points were freedom from cardiac events and AV reinterventions. Survival at 1 year was 97.7% (95% CI, 97.0%-98.5%) in the AV repair cohort vs 96.4% (95% CI, 95.9%-96.9%) in the propensity score-weighted sAVR cohort (log-rank P < .001). Cox regression revealed a significant advantage of AV repair vs sAVR (hazard ratio, 0.68; 95% CI, 0.51-0.90; P < .0001) on 1-year survival, which was independent of age. Cardiac event-free survival at 1 year was 85.7% (95% CI, 483.8%-87.7%) in the AV repair group vs 81.7% (95% CI, 80.7%-82.9%) in the sAVR group (log-rank P < .001). AV reintervention was required in 38 AV repair patients (1.6%) compared with 1.6% in the sAVR cohort (P = .59). AV repair surgery, whenever intraoperatively feasible, is associated with a significantly better 1-year survival and 1-year cardiac event-free survival compared with sAVR.


Reduction of L-methionine selenoxide to seleno-L-methionine by endogenous thiols, ascorbic acid, or methimazole.
Seleno-L-methionine (SeMet) can be oxidized to L-methionine selenoxide (MetSeO) by flavin-containing monooxygenase 3 (FMO3) and rat liver microsomes in the presence of NADPH. MetSeO can be reduced by GSH to yield SeMet and GSSG. In the present study, the potential reduction of MetSeO to SeMet by other cellular components and antioxidants was investigated. Besides GSH, other thiols (L-cysteine, or N-acetyl-L-cysteine) and antioxidants (ascorbic acid and methimazole) also reduced MetSeO to SeMet. This reduction is unique to MetSeO since methionine sulfoxide was not reduced to methionine under similar conditions. The MetSeO reduction by thiols was instaneous and much faster than the reduction by ascorbic acid or methimazole. However, only one molar equivalent of ascorbic acid or methimazole was needed to complete the reduction, as opposed to two molar equivalents of thiols. Whereas the disulfides produced by the reactions of MetSeO with thiols are chemically stable, methimazole disulfide readily decomposed at pH 7.4, 37 degrees C to yield methimazole, methimazole-sulfenic acid, methimazole sulfinic acid, methimazole S-sulfonate, 1-methylimidazole (MI) and sulfite anion. Collectively, the results demonstrate reduction of MetSeO to SeMet by multiple endogenous thiols, ascorbic acid, and methimazole. Thus, oxidation of SeMet to MetSeO may result in depletion of endogenous thiols and antioxidant molecules. Furthermore, the novel reduction of MetSeO by methimazole provides clear evidence that methimazole should not be used as an alternative FMO substrate when studying FMO-mediated oxidation of SeMet.


Comment on "Extinction debt and windows of conservation opportunity in the Brazilian Amazon".
A paper by Wearn et al. (Reports, 13 July 2012, p. 228) yields new insights on extinction debt. However, it leaves out the area dependence of the relaxation process. We show that this is not warranted on theoretical or observational grounds and that it may lead to erroneous conservation recommendations.


Impact of rapid palatal expansion on the size of adenoids and tonsils in children.
Adenoid and tonsillar hypertrophy in children often leads to adverse respiratory symptoms and obstructive sleep apnea (OSA). Current clinical guidelines from the American Academy of Pediatrics and American Academy of Otolaryngology-Head and Neck Surgery recommend tonsillectomy as the first line of pediatric OSA treatment for children with tonsillar hypertrophy. Rapid palatal expansion (RPE) performed by orthodontists improves obstructive sleep apnea in children by reducing nasal airway resistance, increasing nasal volume, raising tongue posture, and enlarging pharyngeal airway. However, the role of RPE in alleviating adenoid and tonsillar hypertrophy remains elusive. In this study, we aim to evaluate the changes in adenoid and palatine tonsil sizes following RPE using 3D volumetric analysis of cone beam computational tomography (CBCT) imaging. In this retrospective cohort study, a total of 60 pediatric patients (mean age: 8.00, range: 5-15, 32 females and 28 males) who had tonsillar hypertrophy (size 3 and 4) were included and divided into the control group (n = 20) and expansion group (n = 40). The control group did not undergo any treatment. The expansion group underwent RPE using a conventional Hyrax expander, activated 0.25 mm per day for 4-6 weeks. Final CBCT scans (T2) were performed 13.8 ± 6.5 months after the initial scan (T1). Pediatric sleep questionnaire (PSQ) and BMI were obtained at each timepoint. Volumetric analysis of adenoid and palatine tonsils was performed using a combination of bony and soft tissue landmarks in CBCT scans through Anatomage Invivo 6 imaging software. Paired t-tests were used to evaluate the difference between the initial and final adenoid and tonsil volumes. p values less than 0.05 were considered statistically significant. Compared to the control group, the expansion group experienced a statistically significant decrease in both adenoid and tonsil volume. There was non-statistically significant increase in volume from T1 to T2 for the control group. For the expansion group, 90.0% and 97.5% of patients experienced significant reduction in adenoid and tonsil volume, respectively. The average volume decrease of adenoids was 16.8% while that of tonsils was 38.5%. The patients had up to 51.6% and 75.4% reduction in adenoid and tonsil size, respectively, following RPE orthodontic treatment. Pearson correlation ranged from 0.88 to 0.99 for each measurement, representing excellent internal consistency. There was a significant reduction in the PSQ scores from 5.81 ± 3.31 to 3.75 ± 2.38 in expansion group (p < 0.001). Our results demonstrated that RPE significantly reduced the size of both adenoid and palatine tonsils and revealed another long-term benefit of RPE treatment. To our knowledge, this is the first study to quantify the changes of adenoids and tonsils following RPE. RPE treatment can be considered as a valid and effective treatment option for pediatric OSA population with narrow high arch palate and adenotonsillar hypertrophy.


Caffeine-inducible ATP release is mediated by Ca2+-signal transducing system from the endoplasmic reticulum to mitochondria.
Adenosine triphosphate (ATP) is released as an autocrine/paracrine signal from a variety of cells. The present study was undertaken to clarify the Ca2+-signal pathway involved in the caffeine-inducible release of ATP from cultured smooth muscle cells (SMC). The release of ATP induced by caffeine (3 mM) was almost completely inhibited by ryanodine and tetracaine, but not by 2-APB, thus being mediated by ryanodine receptors (RyR). The expression of messenger RNA from only RyR-2 was detected in the cells. Furthermore, the induced release was attenuated by mitochondrial inhibitors, rotenone and oligomycin and by Cl- channel blockers, niflumic acid, and 5-nitro-2-(3-phenylpropylamino)-benzoic acid. Increase in Ca2+-signals with fluo 4 and rhod-2 caused by caffeine were reduced by tetracaine and oligomycin plus carbonyl cyanide m-chlorophenylhydrazone, respectively. A close spatial relation between the endoplasmic reticulum (ER) and mitochondria was electromicroscopically observed in the SMC, supporting the existence of a Ca2+-signaling bridge on both the organelli. These results suggest that caffeine stimulates ryanodine receptor (RyR-2) and facilitates a Ca2+-signal transducing system from ER to mitochondria, and then, the signal appears to accelerate the ATP synthesis in mitochondria. In addition, the mitochondrial event may lead further cell signaling to the cell membrane and activates Cl- channels, resulting in the extracellular release of cytosolic ATP.


Novel N'-benzylidene benzofuran-3-carbohydrazide derivatives as antitubercular and antifungal agents.
Tuberculosis constitutes today a serious threat to human health worldwide, aggravated by the increasing number of identified multi-drug resistant strains of Mycobacterium tuberculosis (Mtb), its causative agent, as well as by the lack of development of novel mycobactericidal compounds for the last few decades. A novel series of benzofuran-3-carbohydrazide and its analogs was synthesized and characterized spectroscopically. All the compounds were characterized and screened for in vitro anti-tuberculosis (anti-TB) activity against Mycobacterium tuberculosis H37Rv strains by using resazurin assay utilizing microtiter-plate method (REMA). These compounds also showed good antifungal activity against Candida albicans. Thus, the high level of activity shown by the compounds (8a, 8k) suggests that these compounds could serve as leads for development of novel synthetic compounds with enhanced anti-TB and antifungal activity.


Chronomodulated oxaliplatin plus Capecitabine (XELOX) as a first line chemotherapy in metastatic colorectal cancer: A Phase II Brunch regimen study.
The aim of this study was to evaluate safety and toxicity of chronomodulated capecitabine administered in the morning and at noon according to a specific time schedule (Brunch Regimen: Breakfast and Lunch) as a part of first-line XELOX chemotherapy in patients with metastatic colorectal cancer. A total of 30 treatment-naïve colorectal cancer patients with metastatic disease were included. Oxaliplatin 130 mg/m(2) on day 1 plus chronomodulated oral capecitabine 2000 mg/m(2) per day were administered (50 % dose at 8:00 a.m. and 50 % dose at 12:00 noon on days 1-14, every 21 days). All adverse events, treatment responses and survival were evaluated. In addition, pharmacokinetic profile of capecitabine was examined in a subset of 5 patients. Median age was 57.1 years (range 32-77 years). Median follow-up was 19 months (range 3-36 months). Three patients (10 %) had complete response, 13 patients (43.3 %) had partial response and 4 patients (13.3 %) had stabile disease. Ten patients had progressive disease at their first evaluation (33.3 %). The median progression-free survival (PFS) was 10 months (range 2-36 months). There were no grade 4 toxicities. One patient (3.3 %) had grade 3 neutropenia. Hand-foot syndrome developed in three patients (10 %): 6.6 %, grade 1 and 3.3 %, grade 2. Chronomodulated XELOX seems to represent a promising therapeutic option in the first-line treatment of metastatic colorectal carcinoma due to good tumor control and favorable toxicity profile. Phase III randomized trials are required to assess the actual clinical efficacy and side effect profile of this regimen.


Toxicity of chromium to wheat (Triticum aestivum L.) in two soils: influence of soil properties and chromium form.
The toxicity of Cr to plants depends on Cr form and soil properties. Currently, the phytotoxicity differences of Cr(VI) and Cr(III) in different soils are not clear. In this study, the toxicity of Cr(VI) and Cr(III) to root growth and root morphology of wheat (Triticum aestivum L.) were compared in Shandong fluvo-aquic soil (SD soil) and Jiangxi red soil (JX soil) that is differing in soil properties. The toxicity thresholds of Cr(VI) and Cr(III) on wheat root elongation were determined by fitting the dose-effect curves. Results showed that the 10% and 50% root length inhibitory concentrations (EC10 and EC50) of Cr(III) were 53.1 and 125 times of Cr(VI) in SD soil and 8.11 and 1.36 times of Cr(VI) in JX soil, indicating that Cr(VI) was more toxic to wheat roots than Cr(III) in both soils and the toxicity discrepancy of the two forms of Cr was more prominent in SD soil. Cr(VI) exhibited higher toxicity in SD soil (alkaline) than in JX soil (acidic), whereas Cr(III) showed the opposite pattern. In addition, the ethylene diamine tetraacetic acid extractable Cr (EDTA-Cr) concentrations in soils were correlated well with the relative wheat root elongation (R2=0.854, P<0.01), indicating that soil EDTA-Cr concentration can be used as a predictor of Cr phytotoxicity. Both Cr(VI) and Cr(III) showed significant biphasic dose effects on wheat root morphology (root length, root surface area, root volume, and root tip number) in JX soil. These findings are helpful for the risk evaluation of Cr contamination in agricultural soils.


Obstacles and solutions to screening psoriasis patients for cardiovascular risk factors.
Psoriasis has been linked with cardiovascular risk factors (CVRFs), including the metabolic syndrome, yet many patients with psoriasis remain unscreened. To assess the reasons for lack of screening for CVRFs in psoriasis patients, and the impact of an education programme targeting these deficiencies. All patients with psoriasis, regardless of severity, and all dermatologists working at the National Skin Centre (NSC) in Singapore were surveyed over a 2-month period on their attitudes and knowledge regarding psoriasis and cardiovascular risk. This was followed by a targeted programme which was implemented over 2 months to address these identified deficiencies. Patients and doctors were surveyed a second time to assess the effects of the intervention. Obstacles to screening included lack of patient knowledge, patients not considering screening important, and lack of time during the clinic consultation. After the intervention, there was a significant increase in the proportion of patients who were aware of increased cardiovascular risk in psoriasis (33.0% to 62%), with more patients attending screening (39.1% to 63.2%). While the level of doctors' knowledge did not significantly increase, there was an increase in the proportion of patients who were screened post-intervention (37.1% to 66.2%), and more doctors reported that they were more likely to screen psoriatic patients from an earlier age (30.2% to 58.1%). The obstacles in implementing universal screening for CVRFs in psoriasis patients stem from patient, doctor and system factors. A comprehensive programme targeting all aspects of this ecosystem helps to achieve holistic care for patients with psoriasis.


The effect of insulin therapy algorithms on blood glucose levels in patients following cardiac surgery: A systematic review.
A number of insulin infusion algorithms, with varying methods and effects, have been developed to guide the management of postoperative hyperglycemia in critically ill patients. The objective of this study was to investigate the effect of insulin therapy algorithms on blood glucose levels in patients in critical care environments following cardiac surgery. Types of participants: Adult patients aged 18 or older who were admitted to a critical care environment after cardiac surgery and who received insulin therapy for glycemic control during the acute postoperative phase of their admission. Types of intervention: The intervention of interest was continuous intravenous insulin therapy. Types of studies: Experimental study designs including randomized controlled trials, non-randomized controlled trials and controlled before and after studies published in the English language were included in this review. Types of outcomes: Primary outcomes of interest included objective measures of glycemic control and secondary outcomes of interest included the incidence of adverse events. The search aimed to find both published and unpublished studies through electronic databases, reference lists, key reports and the World Wide Web. An extensive search was undertaken for the following databases: Medline, CINAHL, PubMed, Embase, Scopus, the Cochrane Library, Dare, Social Science Index, ProQuest, and MedNar. Databases were searched up to March 2014. All studies selected were assessed by two reviewers independently for methodological quality prior to inclusion in the review using the standardized Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument critical appraisal tool. Any disagreements that arose between the reviewers were resolved through discussion. Quantitative data was extracted from papers included in the review using the standardized data extraction tool from Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument. All results were subject to double data entry. Statistical pooling of the data in meta-analysis was carried out using Review Manager meta-analysis software where possible. Odds Ratios, Relative Risks, Weighted Means Differences and their 95% Confidence Interval were calculated where appropriate. Where statistical pooling was not possible due to the heterogeneity of the studies the findings are presented in narrative form including tables and figures. Thirteen studies were included in the final review. Pooled data demonstrated significantly improved mean blood glucose levels (Weighted Means Differences -27.24, 95% Confidence Interval: -27.77 - -26.72), p < 0.00001 and achievement of target blood glucose levels range (Relative Risks 1.43, 95% Confidence Interval: 1.18 - 1.72), p = 0.0002, among participants who received the paper nomogram continuous intravenous insulin method of glucose control compared to the bolus regime group. Studies that investigated paper nomogram directed continuous intravenous insulin compared to computer calculator directed continuous intravenous insulin demonstrated a statistically significant improved mean blood glucose levels (Weighted Means Differences -23.74, 95% Confidence Interval: -24.45 - -23.02), p <0.00001 and higher percentage of time in which glucose levels were within the target range in the computer calculator group. A significantly lower incidence (p < 0.05) of hyperglycemia was observed in the computerized calculator directed CII group (1.3 ± 1.2%) compared to the paper nomogram CII (6.5 ± 2%). There is evidence of a benefit of continuous insulin infusions for patients following cardiac surgery with the computer calculator CII method achieving optimal glycemic control. The implementation of a computer calculator CII algorithm allows for individualized patient treatment. However, given the limited availability of the computer based algorithm, the implementation of a paper based algorithm would be justified. Future studies to compare the methods of computer calculator directed CII to paper nomogram directed CII should be undertaken using more rigorous research designs such as randomized controlled trials with sufficiently powered sample sizes. Definitions for both hypoglycemia and hyperglycemia should be standardized.


Effects of dose reduction on bone strength prediction using finite element analysis.
This study aimed to evaluate the effect of dose reduction, by means of tube exposure reduction, on bone strength prediction from finite-element (FE) analysis. Fresh thoracic mid-vertebrae specimens (n = 11) were imaged, using multi-detector computed tomography (MDCT), at different intensities of X-ray tube exposures (80, 150, 220 and 500 mAs). Bone mineral density (BMD) was estimated from the mid-slice of each specimen from MDCT images. Differences in image quality and geometry of each specimen were measured. FE analysis was performed on all specimens to predict fracture load. Paired t-tests were used to compare the results obtained, using the highest CT dose (500 mAs) as reference. Dose reduction had no significant impact on FE-predicted fracture loads, with significant correlations obtained with reference to 500 mAs, for 80 mAs (R2 = 0.997, p < 0.001), 150 mAs (R2 = 0.998, p < 0.001) and 220 mAs (R2 = 0.987, p < 0.001). There were no significant differences in volume quantification between the different doses examined. CT imaging radiation dose could be reduced substantially to 64% with no impact on strength estimates obtained from FE analysis. Reduced CT dose will enable early diagnosis and advanced monitoring of osteoporosis and associated fracture risk.


Transition of patients with mucopolysaccharidosis from paediatric to adult care.
Mucopolysaccharidoses (MPS) are rare disorders associated with enzyme deficiencies, resulting in glycosaminoglycan (GAG) accumulation in multiple organ systems. As patients increasingly survive to adulthood, the need for a smooth transition into adult care is essential. Using case studies, we outline strategies and highlight the challenges of transition, illustrating practical solutions that may be used to optimise the transition process for patients with MPS disorders. Seven MPS case studies were provided by four European inherited metabolic disease centres; six of these patients transferred to an adult care setting and the final patient remained under paediatric care. Of the patients who transferred, age at the start of transition ranged between 14 and 18 years (age at transfer ranged from 16 to 19 years). While there were some shared features of transition strategies, they varied in duration, the healthcare professionals involved and the management of adult patients with MPS. Challenges included complex symptoms, patients' unwillingness to attend appointments with unfamiliar team members and attachment to paediatricians. Challenges were resolved by starting transition at an early age, educating patients and families, and providing regular communication with and reassurance to the patient and family. Sufficient time should be provided to allow patients to understand their responsibilities in the adult care setting while feeling assured of continued support from healthcare professionals. The involvement of a coordinated multidisciplinary team with expertise in MPS is also key. Overall, transition strategies must be comprehensive and individualised to patients' needs.


Semi-crystalline sulfonated poly(ether ketone) proton exchange membranes: The trade-off of facile synthesis and performance.
Improving the performance of proton exchange membranes (PEMs) through the synthesis of sulfonated polymers with elaborate molecular structures has received extensive approval. However, the tedious synthetic process and consequently high costs restrain their possible substitution for Nafion, a classic PEM material. Herein, a series of semi-crystalline sulfonated poly(ether ketone)s with fluorene-based units were prepared via direct copolymerization of commercially available monomers and followed post-sulfonation, namely SPEK-FD-x, where × represents the molar ratio of the fluorene-containing monomer to the employed bisphenol monomers. The entire synthetic pathway was facile without involving hardly accessible materials. Subsequently, various properties of SPEK-FD-x membranes were investigated and further compared with Nafion 117. Due to the formation of the well-defined hydrophilic-hydrophobic microphase separation morphology and the reinforcement of the PEK crystalline regions, the SPEK-FD-x membranes exhibited outstanding proton conductivity, resistance for methanol permeation, as well as dimensional, thermal, oxidative, and mechanical stability. Among them, the overall behavior of the SPEK-FD-25 membrane was comparable to or even greater than that of Nafion 117, most importantly, it also performed decently in both H2/air fuel cells and direct methanol fuel cells. Therefore, with the straightforward synthesis and superior performance, the SPEK-FD-x membranes may serve as a promising alternative to Nafion.


Taste thresholds in man are differentially influenced by hydrocortisone and dexamethasone.
The present study focused on sensory processing (taste threshold) in healthy young men given different cortisol doses within the normal physiological range. It aimed to differentiate the effects of dexamethasone, a synthetic pure glucocorticoid, compared to hydrocortisone, which has both glucocorticoid and mineralocorticoid properties. In a double-blind, cross-over design, 18 male subjects participated in three sessions. Subjects were pretreated orally with hydrocortisone (50 mg), dexamethasone (2 mg) or placebo. Taste detection was tested by a forced-choice three stimulus drop technique to determine detection acuity and a signal detection procedure to determine the ability to detect differences in NaCl concentration. Cortisol concentrations were determined in blood and saliva. Hydrocortisone and dexamethasone had opposite effects on taste detection acuity. With the highest cortisol levels after intake of hydrocortisone, subjects made more errors in detection trials with respect to stimuli close to the absolute taste detection threshold than after intake of dexamethasone. Detection of differences was impaired by both glucocorticoids. This type of behavioral study in man may help clarify the roles of heterogeneous corticosteroid receptor systems within the human brain.


Studies on the effects of the narcotic alkaloids, cocaine, morphine, and codeine on nonenzymatic lipid peroxidation in rat brain mitochondria.
This paper presents evidence of studies on the effects of the narcotic alkaloids, cocaine hydrochloride, morphine sulfate, and codeine phosphate, on nonenzymatic lipid peroxidation in rat brain mitochondria. These organelles abound in polyunsaturated fatty acids and are thus susceptible to oxidative attack. Lipid peroxidation was indexed mainly by assaying the extent of malonaldehyle (MDA) production and also the formation of fluorescent products in the course of the reaction. We found that morphine sulfate lowered fluorescence while the other two alkaloids showed no effect on lipid peroxidation in the absence of the inducers, 1.0 mM ascorbic acid or 0.1 mM ferrous sulfate. The apparent antioxidative nature of morphine sulfate was also observed in its effects on induced and noninduced MDA production, both cocaine hydrochloride and codeine phosphate stimulated MDA production by about 20% in the absence of any inducers. This paper also attempts to draw a structure-activity relationship for the antioxidative action of opium alkaloids, which we postulated to be due to the chelating capability of the alkaloid molecule.


Mechanistic and Therapeutic Approaches to Occupational Exposure-Associated Allergic and Non-Allergic Asthmatic Disease.
Occupational lung disease, including asthma, is a significant cause of disability worldwide. The dose, exposure frequency, and nature of the causal agent influence the inflammatory pathomechanisms that inform asthma disease phenotype and progression. While surveillance, systems engineering, and exposure mitigation strategies are essential preventative considerations, no targeted medical therapies are currently available to ameliorate lung injury post-exposure and prevent chronic airway disease development. This article reviews contemporary understanding of allergic and non-allergic occupational asthma mechanisms. In addition, we discuss the available therapeutic options, patient-specific susceptibility and prevention measures, and recent scientific advances in post-exposure treatment conception. The course of occupational lung disease that follows exposure is informed by individual predisposition, immunobiologic response, agent identity, overall environmental risk, and preventative workplace practices. When protective strategies fail, knowledge of underlying disease mechanisms is necessary to inform targeted therapy development to lessen occupational asthma disease severity and occurrence.


Transcriptional regulation of Saccharomyces cerevisiae CYS3 encoding cystathionine gamma-lyase.
In studying the regulation of GSH11, the structural gene of the high-affinity glutathione transporter (GSH-P1) in Saccharomyces cerevisiae, a cis-acting cysteine responsive element, CCGCCACAC (CCG motif), was detected. Like GSH-P1, the cystathionine gamma-lyase encoded by CYS3 is induced by sulfur starvation and repressed by addition of cysteine to the growth medium. We detected a CCG motif (-311 to -303) and a CGC motif (CGCCACAC; -193 to -186), which is one base shorter than the CCG motif, in the 5'-upstream region of CYS3. One copy of the centromere determining element 1, CDE1 (TCACGTGA; -217 to -210), being responsible for regulation of the sulfate assimilation pathway genes, was also detected. We tested the roles of these three elements in the regulation of CYS3. Using a lacZ-reporter assay system, we found that the CCG/CGC motif is required for activation of CYS3, as well as for its repression by cysteine. In contrast, the CDE1 motif was responsible for only activation of CYS3. We also found that two transcription factors, Met4 and VDE, are responsible for activation of CYS3 through the CCG/CGC and CDE1 motifs. These observations suggest a dual regulation of CYS3 by factors that interact with the CDE1 motif and the CCG/CGC motifs.


Partially purified bitter gourd (Momordica charantia) peroxidase catalyzed decolorization of textile and other industrially important dyes.
The aim of this study was to evaluate the enzymatic action of partially purified bitter gourd peroxidase for the degradation/decolorization of complex aromatic structures. Twenty-one dyes, with a wide spectrum of chemical groups, currently being used by the textile and other important industries have been selected for the study. Here, for the first time we have shown peroxidases from Momordica charantia (300 EU/gm of vegetable) to be highly effective in decolorizing industrially important dyes. Dye solutions, containing 50-200 mg dye/l, were used for the treatment with bitter gourd peroxidase (specific activity of 99.0 EU/mg protein). M. charantia peroxidases were able to decolorize most of the textile dyes by forming insoluble precipitate. When the textile dyes were treated with increasing concentration of enzyme, it was observed that greater fraction of the color was removed but four out of eight reactive dyes were recalcitrant to decolorization by bitter gourd peroxidase. Step-wise addition of enzyme to the decolorizing reaction mixture at the interval of 1h further enhanced the dye decolorization. The rate of decolorization was enhanced when the dyes were incubated with fixed quantity of enzyme for increasing times. Decolorization of non-textile dyes resulted in the degradation and removal of dyes from the solution without any precipitate formation. Decolorization rate was drastically increased when the textile and other industrially important non-textile dyes were treated with bitter gourd peroxidase in presence of 1.0 mM 1-hydroxybenzotriazole. Complex mixtures of dyes were prepared by taking three to four reactive textile and non-textile dyes in equal proportions. Each mixture was decolorized by more than 80% when treated with the enzyme in presence of 1.0 mM 1-hydroxybenzotriazole. Our data suggest that the peroxidase/mediator system is an effective biocatalyst for the treatment of effluents containing recalcitrant dyes from textile, dye manufacturing, dyeing and printing industries.


Outcomes of Surgery for intramuscular Haemangiomas in the Extremities.
The objective of this case-series study was an assessment of outcomes of surgery for intramuscular haemangiomas in the extremities. Three women and one man with a mean age of 28 (23 - 34) years were operated on for intramuscular haemangiomas in the extremities, 3 in the forearms, and 1 in the calf. Three of them, 2 after resection of tumours from the forearm, and one after resection of the tumour in the calf, were available for follow-up assessment at an average of 1.5 (1 - 2) years after surgery. For patients with the tumour in the forearm, preoperative and at the follow-up examination pain was registered with use of the numeric rank scale (NRS), grip strength with the Jamar dynamometer, and function of the extremity with the quickDASH questionnaire. In the patient with the lower limb involvement, pain at the operation site, and efficiency (dexterity) of gait were evaluated. All 3 patients with a follow-up examination reported significant reduction of pain. With regard to grip strength and hand function, one patient had significant improvement, whereas in the other, there were no real changes compared to preoperative. The patient with the calf involvement had no symptoms and walked normally. Over the follow-up period, no recurrence was noted. The results of this small case-series study show that operative treatment of these rare tumours is safe and effective, however, it may be challenging in some cases.


Discrepancies between medication records of anticoagulation clinics and pharmacy records.
To determine whether there were discrepancies between with coumarin anticoagulants interacting medications recorded in medical files of anticoagulation clinics (AC-records) and computerized records of community pharmacies (pharmacy records). A descriptive study was conducted at two Dutch anticoagulation clinics (AC's). Records of with coumarin anticoagulants interacting drugs at the AC's were compared with the pharmacy records. A drug registered in the pharmacy records but not in the AC-records, was recorded as a discrepancy, while a drug registered in AC-records as well as in pharmacy records, was recorded as a match. Of the 117 identified interacting drugs registered in pharmacy records 32 (27%) were not registered in the AC-records. In four out of seven patients of whom the use of a pharmacokinetically interacting drug was not registered in the AC-records, several INR-values exceeded the upper therapeutic range. This study demonstrates that a substantial percentage of drugs of which an interaction with coumarin anticoagulants can be expected, is not registered in the medical files of anticoagulation clinics.


Effects of carnosine on bilharzial infestation in hamsters: biochemical and histochemical studies.
We tested the ability of carnosine to improve some liver disorders induced by Schistosoma mansoni parasite in hamsters (Mesocricetus auratus). Results indicate that parasitic infestation induced elevation in serum alkaline phosphatase, gamma-glutamyl transferase, aspartate aminotransferase and procollagen III peptide as a marker of liver fibrosis. Administration of carnosine (10 mg/day) for 15 days either concurrent with infection, 2 and 4 weeks post-infestation was effective in reducing differential worm burden. It was also effective in renormalizing blood glucose level depending on the time course. The most evident effect of carnosine was on serum procollagen III peptide level, which was lowered in infested groups treated with carnosine. Histopathological studies confirmed the potential use of carnosine for intervention in schistosomiasis.


Epidemiology of borrelia infections in Austria.
From April 1984 to July 1985 873 cases of Borrelia infections were registered at the Hygiene Institute of the University of Vienna. 2609 serum samples of these patients were investigated for antibodies against B. burgdorferi by means of IFA- and ELISA-tests. Erythema chronicum migrans (ECM) was recognized in 60.9% of patients, neurological abnormalities were recorded in 23.4% of which the majority manifested themselves as polyradiculitis and meningopolyneuritis (MPN). Acrodermatitis chronica atrophicans (ACA) was recognized in 11.5%. A small number of patients suffered from Lymphadenosis cutis benigna (LCB), arthritis and cardiac abnormalities. Sixty percent of patients were females and 40% males. Infections were found in all age groups ranging from 2-83 years in females and 1-85 years in males. Tick- or insect-bites prior to the onset of illness were reported by 47.2% and 15.6% of patients, respectively. The main vector is the hard tick Ixodes ricinus. Flying insects from the family tabanidae, i.e. Chrysops caecutiens and Haematopota species, must also be considered as transmitters. Antibodies to B. burgdorferi were found in 22.3%, 93.6% and 100% of sera from patients with ECM, MPN and ACA, respectively. Six of 11 patients with LCB and all with arthritis and cardiac abnormalities showed serologic reactivity. Geographically, Borrelia infections are distributed in all states of Austria. The seasonal distribution of cases show a peak in July and August, but the onset of clinical manifestation could be observed throughout the year. These results present Austria as an area where tick- or insect-borne Borrelia infections are very frequent and endemic in all Austrian states.


Mitral valve prolapse and pre-excitation.
Two out of 118 patients with mitral valve prolapse were found to have pre-excitation. The presence of mitral valve prolapse in one patient with Lown-Ganong-Levine syndrome and the persistence of prolapse in the presence and absence of pre-excitation in another patient with intermittent type B Wolff-Parkinson-White syndrome suggest that mitral valve prolapse in pre-excitation syndrome may not be secondary to the abnormal activation pattern of the left ventricle, which has been suggested as a possible mechanism by some investigators.


Social variables for replication of studies using mean scores of social support, self-care, and fibromyalgia knowledge: a cross-sectional study.
To investigate biopsychosocial variables that contribute to explaining social support, self-care, and fibromyalgia knowledge in patients with fibromyalgia. A cross-sectional study. We built ten models of predictive variables (schooling, ethnicity, associated diseases, body regions affected by pain, employment status, monthly income, marital status, health level, medication, sports activities, interpersonal relationships, nutrition level, widespread pain, symptom severity, cohabitation, dependent people, number of children, social support, self-care, and fibromyalgia knowledge) and individually tested their explanatory performance to predict mean scores on the Fibromyalgia Knowledge Questionnaire (FKQ), Medical Outcomes Study's Social Support Scale (MOS-SSS), and Appraisal of Self-Care Agency Scale-Revised (ASAS-R). We used analysis of variance to verify the association among all variables of mathematically adjusted models (F-value ≥ 2.20) and we reported only models corrected with p < 0.05 and R2 > 0.20. One hundred and ninety people with fibromyalgia (aged 42.3 ± 9.7 years) participated in the study. Our results show that the variables schooling, ethnicity, body regions affected by pain, frequency of sports activities, dependent people, number of children, widespread pain, social support, and self-care determine 27% of the mean FKQ scores. Marital status, self-care, and fibromyalgia knowledge determine 22% of mean MOS-SSS scores. Schooling, ethnicity, employment status, frequency of sports activities, nutrition level, cohabitation, number of children, social support, and fibromyalgia knowledge determine 30% of the mean ASAS-R scores. Studies using mean scores of social support, self-care, and fibromyalgia knowledge should collect and analyze the social variables described in the present study.


Patterns of development in young children with autism.
To determine the extent to which the developmental profile of children less than 4 years can help in distinguishing children with autism from children with developmental delay. Subjects were 32 children with autism as per the DSM IV criteria and 32 children with developmental delay matched on chronological and academic age. The Developmental Profile II was used to assess the developmental functioning in five domains including physical, social, self help, academic, and communication. The two groups showed significantly different developmental profiles and these differences were accounted for mainly by significantly lower social skills and superior motor skills in the autistic group as compared to the developmentally delayed group. Developmental Profile II may help in distinguishing young children with autistic disorder from non-autistic children with comparable developmental delays.


Noncardiogenic pulmonary edema as a rare complication of blood transfusions. A case report.
A woman was treated for leukoagglutinin-induced noncardiogenic pulmonary edema resulting from a blood transfusion.


Sulfation of Heparan and Chondroitin Sulfate Ligands Enables Cell-Specific Homing of Nanoprobes.
Demystifying the sulfation code of glycosaminoglycans (GAGs) to induce precise homing of nanoparticles in tumor cells or neurons influences the development of a potential drug- or gene-delivery system. However, GAGs, particularly heparan sulfate (HS) and chondroitin sulfate (CS), are structurally highly heterogeneous, and synthesizing well-defined HS/CS composed nanoparticles is challenging. Here, we decipher how specific sulfation patterns on HS and CS regulate receptor-mediated homing of nanoprobes in primary and secondary cells. We discovered that aggressive cancer cells such as MDA-MB-231 displayed a strong uptake of GAG-nanoprobes compared to mild or moderately aggressive cancer cells. However, there was no selectivity towards the GAG sequences, thus indicating the presence of more than one form of receptor-mediated uptake. However, U87 cells, olfactory bulb, and hippocampal primary neurons showed selective or preferential uptake of CS-E-coated nanoprobes compared to other GAG-nanoprobes. Furthermore, mechanistic studies revealed that the 4,6-O-disulfated-CS nanoprobe used the CD44 and caveolin-dependent endocytosis pathway for uptake. These results could lead to new opportunities to use GAG nanoprobes in nanomedicine.


Reflux Finding Score (RFS) a Quantitative Guide for Diagnosis and Treatment of Laryngopharyngeal Reflux.
The study was under taken to know the prevalence of reflux signs in an individuals with throat complaints on the basis of reflux finding score (RFS) and quantitatively assess the effect of treatment. A cross-sectional study was done to evaluate the presence of laryngo-pharyngeal reflux signs in patients visiting ENT clinic with throat or voice problems in central India. There were 80 patients included in the study from 2017 to 2018 individuals. They were questioned regarding their symptoms. Their pharyngeal findings on rigid 70° laryngoscopy were viewed and RFS was made. The patients were reviewed at monthly intervals. Laryngopharyngeal reflux changes were seen in 36 of the 80 patients (45%). The reflux was graded as per the reflux finding score. The score ranged from 7 to maximum of 17 out of 26 in the patients with LPRD. Majority of the patients the score decreased with lifestyle changes and pantaprazole twice daily. There was poor response in 5% (4) patients, who were then advised to undergo upper gastro intestinal endoscopy for further assessment. Laryngopharyngeal reflux has become a very common entity in urban lifestyle. On careful examination the signs can be picked and assessed with the RFS, which is a very useful tool to grade and reassess patient on subsequent follow up.


HeLa cell messenger RNAs of widely differing sizes encode certain heat shock proteins in the Mr region of 72 000-74 000.
Cloned cDNA sequences coding for specific 72 000-74 000 Mr HeLa cell heat shock proteins (HSPs) have been used as probes to examine cytoplasmic and nuclear RNA of heat shocked HeLa cells. The mRNAs for these HSPs vary widely in size. Whilst the beta-, delta- and epsilon-HSPs are encoded in mRNAs of 1.9 kb, the gamma-HSP arises from an mRNA three times that size. A search for putative nuclear precursors to these mRNAs revealed high Mr candidates at 15.8 kb which accumulate 1-2 h after the initial heat shock, thus supporting the notion that transcriptional control is important in the initial heat shock response.


The danger of an inadequate water intake during prolonged exercise. A novel concept re-visited.
To prevent thermal injuries during distance running, the American College of Sports Medicine proposes that between 0.83 and 1.65 l of water should be ingested each hour during prolonged exercise. Yet such high rates of fluid intake have been reported to cause water intoxication. To establish the freely-chosen rates of fluid intake during prolonged competitive exercise, we measured fluid intake during, body weight before and after, and rectal temperature after competition in a total of 102 runners and 91 canoeists competing in events lasting from 170-340 min. Fluid intakes during competition ranged from 0.29-0.62 l.h-1; rates of water loss ranged from 0.69-1.27 l.h-1 in the runners; values were lower in the canoeists. Mean post-race rectal temperatures ranged from 38.0-39.0 degrees C. There was no relationship between the degree of dehydration and post-race rectal temperature. We conclude that hyperthermia is uncommon in prolonged competitive events held in mild environmental conditions, and that exercise intensity, not the level of dehydration, is probably the most important factor determining the postexercise rectal temperature. During prolonged exercise in mild environmental conditions, a fluid intake of 0.5 l.h-1 will prevent significant dehydration in the majority of athletes.


Formation of aliphatic amine precursors of N-nitrosodimethylamine after oral administration of choline and choline analogues in the rat.
Trimethylamine and dimethylamine are important precursors of N-nitrosodimethylamine, which is a potent carcinogen in a wide variety of animal species. Choline, a component of the normal human diet, is metabolized by bacteria within the intestine to form trimethylamine and dimethylamine. However, animals on a choline-free diet continue to excrete some trimethylamine and dimethylamine, suggesting that other dietary precursors of these methylamines might exist. To determine whether C-N bond cleavage by the intestinal bacteria is specific to the choline molecule, we measured monomethylamine, dimethylamine, trimethylamine and trimethylamine oxide excretion in rat urine after the administration of compounds that shared structural features with choline. Water, choline, dimethylaminoethanol, diethylaminoethanol, phosphocholine, betaine, carnitine, beta-methylcholine or dimethylaminoethyl chloride were administered by orogastric intubation, and the urine was collected for 24 hr. Administration of choline (15 mmol/kg body weight) resulted in increased urinary excretion of dimethylamine, trimethylamine and trimethylamine oxide (increases of approximately twofold, 500-fold and 50-fold, respectively). Of the administered choline, 12% was converted to trimethylamine or trimethylamine oxide and excreted in the urine within 24 hr. Phosphocholine administration resulted in similar increases in dimethylamine, trimethylamine and trimethylamine oxide excretion by rats. Modification of the ethyl-backbone or quaternary amine end of the choline molecule resulted in marked suppression of methylamine formation. Though administration of some analogues of choline (methylcholine, betaine and carnitine) resulted in the formation of small amounts of trimethylamine or trimethylamine oxide, and the administration of others (dimethylaminoethanol and dimethylaminoethyl chloride) resulted in the formation of some dimethylamine, the amounts formed were minimal compared with the amounts of trimethylamine and trimethylamine oxide formed after choline administration. Thus, of the many components of foods, only choline and its esters are likely to be significant substrates for trimethylamine and dimethylamine formation. How then can we explain the persistence of trimethylamine and dimethylamine excretion observed in choline-deficient rats? We suggest that endogenous (non-bacterial) synthesis of trimethylamine and dimethylamine occurs within some tissue of the rat.


[Diseases of the adnexa in the tropics: amnion membrane transplantation for noninfectious trachoma-associated corneal ulcers].
Corneal ulcers with fornix shortening associated with late stages of cicatrizing trachoma contribute significantly to blindness in many developing countries. We report on the outcome of ocular surface and fornix reconstruction using amnion membrane transplantation. From 2001 to 2005, cryopreserved human amnion membrane without mitomycin C was grafted to 25 eyes of 17 patients with trophic corneal ulcers and symblepharon (cicatrizing trachoma: 19 eyes of 14 patients, Stevens-Johnson syndrome: 4 eyes of 2 patients, alkali burns: 2 eyes of 1 patient) in a controlled case series. Follow-up was done up to 6 months. Fischer's exact probability test. Of 25 eyes, 9 of 19 eyes with trachoma, 3 of 4 eyes with Stevens-Johnson syndrome, and 2 of 2 eyes with chemical burns showed complete reepithelialization and stromal recovery after 28-35 days (mean: 31+/-2.3 days). The primary success rate of trachoma eyes was not significantly different from the other indications (p=0.256). At 6 months post-op, 15 of 19 trachoma eyes (79%) compared to 2 of 6 non-trachoma eyes (33.3%) had developed a recurrence of symblephara (p=0.0592), and 13 of 15 eyes (86.6%) with a cicatricial trachoma compared to 1 of 6 with non-trachoma diagnosis experienced a recurrence of corneal vascularization (difference nonsignificant: p=0.1752). Persistent long-term reepithelialization was observed only in 1 of 19 trachoma eyes (5.3%) versus 4 of 6 non-trachoma eyes (66.7%, p=0.005); 3 of 19 trachoma eyes with a recurrence of ulcers had perforated after 6 months. Human amnion membrane without mitomycin C can be used for ocular surface reconstruction in selected patients with cicatrizing trachoma. Its efficacy in the long-term rehabilitation of cicatrizing trachoma seems to be limited due to the progressive scarring.


Collection method for chemical particulates on surfaces with detection using thermal desorption-ion trap mass spectrometry.
Successful analysis of particulate/low vapor pressure analytes such as explosives and toxic chemicals, and commercial pesticides require new sampling tools that enable detection of these analytes using current vapor phase detection instruments. We describe a sampling approach that uses stainless steel screens coated with a sticky polydimethyl siloxane (PDMS) coating to capture particulates from surfaces. Preliminary results for the collection of dimethyl methylphosphonate (DMMP) sorbed onto silica gel (SG) particulates (DMMP/SG) from a surface with subsequent analysis by thermal desorption-cylindrical ion trap mass spectrometry (TD-CITMS) are reported.


Fluorescence and Raman spectroscopy.
Table 2 provides a summary of selected in vivo fluorescence and Raman studies performed in BE. Although the findings from these studies appear promising, these techniques are still under development, and it is anticipated that technological refinements will further enhance their diagnostic accuracy. Ultimately, however, large-scale prospective clinical trials are required to determine their true diagnostic potential in BE and other sites. Ideally, the instrumentation of choice would be a real-time endoscopic system that combines excellent diagnostic accuracy with wide-area sampling. In this regard, fluorescence imaging is most appealing, although a variety of issues remain to be resolved, including the choice between autofluorescence versus drug-induced fluorescence and the problematic distinction between dysplastic (true positive) and confounding background metaplastic fluorescence (false positive), among others. It is also not clear whether exogenous fluorophores are necessary to achieve clinically useful sensitivity and specificity for lesion detection in BE. Point spectroscopic techniques, either fluorescence or Raman scattering, are inherently limited by the small volume of tissue (biopsy specimen size) they sample, but more detailed information can be extracted from the spectra, which may increase diagnostic accuracy. Moreover, it may be that the optimal system will be a combination of multiple optical spectroscopic or imaging techniques (multimodality approach), as suggested by Georgakoudi et al. For instance, a lesion could be detected by fluorescence imaging and its dysplastic nature characterized (graded) by Raman spectroscopy. In this era of cost containment, however, the critical challenge is to demonstrate whether an increase in diagnostic accuracy merits investment in costly technology, regardless of the technique used.


Metastatic malignant melanoma in the lung. Diagnosis by thin-needle aspiration biopsy.
Two patients had malignant melanoma, metastatic to the lung, as established by percutaneous needle aspiration biopsy. To the best of our knowledge, this has not been reported previously.


Prehospital and Emergency Management.
Burn care in the prehospital and emergency settings requires rapid assessment of airway, breathing, and circulation. Intubation (if indicated) and fluid resuscitation are most important in emergency burn care. Total body surface area burned and depth of burn are important early assessments that help guide resuscitation and disposition. Burn care in the emergency department further includes carbon monoxide and cyanide toxicity evaluation and management.


Family needs and burdens of mentally ill offenders.
A growing number of research projects have been devoted to the study of needs, burdens and intervention programmes of families of psychiatric patients due to the emphasis on deinstitutionalization and community integration. Although it is noted that burdens for families when looking after a patient with a criminal history are even heavier and more complicated, studies on identifying family needs and burdens for mentally ill offenders have been very limited. This paper reviews literature on family burdens and studies on family needs for psychiatric patients with a forensic history. Methodological problems of available studies are discussed. In addition, a theoretical model that can be used as a conceptual guide for the study of burdens of families of mentally ill offenders is postulated. Directions for further research are discussed.


Adolescent Depression Curriculum Impact on Pediatric Residents' Knowledge and Confidence to Diagnose and Manage Depression.
Despite the need for pediatricians to diagnose and manage adolescent depression, few pediatric residency curricula exist. This study evaluated the impact of an adolescent depression curriculum on pediatric residents' knowledge and confidence to manage depression. A novel, case-based, adolescent depression curriculum simulating patient-provider continuity was developed and implemented within an adolescent medicine (AM) rotation. The curriculum addressed seven domains critical for diagnosis and management of adolescent depression. Participants were recruited from the pediatric residency at one institution. A survey assessed residents' demographics, prior training, and self-assessed knowledge and confidence within each domain using a retrospective pre-post evaluation. Wilcoxon signed-rank test evaluated changes in knowledge and confidence. Forty-two of a total 51 residents (82%) completed the curriculum and survey during their AM rotation. Residents reported that within their continuity clinic, 45% (n = 19) had never initiated medication for depression, and 60% (n = 25) did not manage their adolescent patients' depression medications. Comparisons before and after participation in the curriculum, using the retrospective pre-post survey, demonstrated increased self-assessed knowledge (p < .001, for each domain) and confidence (p < .001, for each domain). In this study, few residents reported experience initiating medication or managing adolescent depression in the continuity clinic. Residents demonstrated increased self-assessed knowledge and confidence to diagnose and manage adolescent depression after participation in a case-based adolescent depression curriculum simulating patient-provider continuity. Incorporation of training on management of adolescent depression into AM rotation may be a feasible option to standardize training within pediatric residency.


"It didn't bring back the old me but helped me on the path to the new me": exploring posttraumatic growth in British veterans with PTSD.
This study explores the role of scuba diving therapy in growth experiences of ex-servicemen. Previous research has focused on difficulties arising from re-entering civilian life after deployment. Known mental health challenges occurring after severe combat related trauma exposure include depression, anxiety, and posttraumatic stress disorder (PTSD). However, less is known about the potential positive transformation which can occur when individuals navigate these challenges. Known facilitators of this positive transformation, often referred to as posttraumatic growth (PTG), are still sparse in this participant pool. This study utilized an in-depth qualitative approach of interpretative phenomenological analysis utilizing semi-structured interviews. A homogeneous sample of five male British ex-service personnel with a diagnosis of PTSD who identified with PTG was recruited. All participants reported positive mental health benefits from diving with four themes emerging: human connection; meaningful leisure; embodiment; and the calm. Scuba diving appeared to afford instant access to lasting relief of anxiety, stress, and symptoms of PTSD and reduction of physical symptoms of their trauma connected to underwater weightlessness. The reduction of PTSD symptoms carved space for PTG, facilitated through a meaningful leisure environment with opportunities for human connection with individuals who had gone through similar experiences.Implications for rehabilitationVeterans with posttraumatic stress disorder (PTSD) respond less well to conventional treatments for PTSD than civilian populations.Scuba diving has the potential to benefit veterans by giving access to relief from anxiety and symptoms of PTSD, such as hypervigilance and invasive thoughts.Scuba diving not only reduces symptoms of physical and psychological ill health but can facilitate wellbeing and growth.Scuba diving, as a meaningful leisure activity, could potentially enhance medical and psychological therapy.


Long-term expansion of alveolar stem cells derived from human iPS cells in organoids.
The stable expansion of tissue-specific stem cells in vitro has contributed to research on several organs. Alveolar epithelial type II (AT2) cells function as tissue stem cells in the lung, but robust models for studying human AT2 cells are lacking. Here we report a method for the efficient generation and long-term expansion of alveolar organoids (AOs) harboring SFTPC+ alveolar stem cells derived from human induced pluripotent stem cells (hiPSCs). hiPSC-derived SFTPC+ cells self-renewed, with transcriptomes and morphology consistent with those of AT2 cells, and were able to differentiate into alveolar epithelial type I (AT1)-like cells. Single-cell RNA-seq of SFTPC+ cells and their progenitors demonstrated that their differentiation process and cellular heterogeneity resembled those of developing AT2 cells in vivo. AOs were applicable to drug toxicology studies recapitulating AT2-cell-specific phenotypes. Our methods can help scientists overcome the limitations of current approaches to the modeling of human alveoli and should be useful for disease modeling and regenerative medicine.