Spinal mechanisms of NPY analgesia.
We review previously published data, and present some new data, indicating that spinal application of neuropeptide Y (NPY) reduces behavioral and neurophysiological signs of acute and chronic pain. In models of acute pain, early behavioral studies showed that spinal (intrathecal) administration of NPY and Y2 receptor agonists decrease thermal nociception. Subsequent neurophysiological studies indicated that Y2-mediated inhibition of excitatory neurotransmitter release from primary afferent terminals in the substantia gelatinosa may contribute to the antinociceptive actions of NPY. As with acute pain, NPY reduced behavioral signs of inflammatory pain such as mechanical allodynia and thermal hyperalgesia; however, receptor antagonist studies indicate an important contribution of spinal Y1 rather than Y2 receptors. Interestingly, Y1 agonists suppress inhibitory synaptic events in dorsal horn neurons (indeed, well known mu-opioid analgesic drugs produce similar cellular actions). To resolve the behavioral and neurophysiological data, we propose that NPY/Y1 inhibits the spinal release of inhibitory neurotransmitters (GABA and glycine) onto inhibitory neurons, e.g. disinhibition of pain inhibition, resulting in hyporeflexia. The above mechanisms of Y1- and Y2-mediated analgesia may also operate in the setting of peripheral nerve injury, and new data indicate that NPY dose-dependently inhibits behavioral signs of neuropathic pain. Indeed, neurophysiological studies indicate that Y2-mediated inhibition of Ca(2+) channel currents in dorsal root ganglion neurons is actually increased after axotomy. We conclude that spinal delivery of Y1 agonists may be of use in the treatment of chronic inflammatory pain, and that the use of Y1 and Y2 agonists in neuropathic pain warrants further consideration.


Successful Treatment of Coexisting Paraganglioma of the Retroperitoneum and Urinary Bladder by Intermediate-Dose 131I-MIBG Therapy: A Case Report.
Paragangliomas (PGLs) are rare neuroendocrine neoplasms of the autonomic nervous system dispersed from the skull base to the pelvic floor. We reported an extremely rare case with coexisting PGL of the retroperitoneum and urinary bladder. The patient complained of episodes of severe headache and palpitation during micturition, with a 1-year history of uncontrolled hypertension. The (131)I-metaiodobenzylguanidine ((131)I-MIBG) scintigraphy revealed high uptake in both of the retroperitoneum and urinary bladder mass accompanied with increasing 24 hour urinary norepinephrine and epinephrine. The patient received 6 doses of high-specific activity (131)I-MIBG from October 2009 to April 2015, each treatment dose was 400 mCi. The patient got symptomatic, hormonal, and radiographic tumor complete response without life-threatening adverse events.Intermediate-dose (131)I-MIBG therapy may be an alternative choice for patients with multicentric PGLs with positive MIBG scintigraphy.


Severe radial artery spasm causing entrapment of the Terumo radial to peripheral destination slender sheath: a case report.
Radial access for lower-extremity peripheral vascular interventions (PVIs) has been limited due to inadequate equipment lengths. The Terumo R2P Destination Slender sheath is a relatively new sheath designed for these interventions. However, complications related to this sheath or access strategy for lower-extremity PVI have not been reported. A 69-year-old woman presented with purple discolouration of her 1st and 5th toes of the left foot for approximately 1 month. Lower-extremity arterial duplex ultrasound showed mid left superficial femoral artery (SFA) greater than 90% stenosis. Peripheral angiogram was performed via the left radial artery and this confirmed the presence of severe left SFA stenosis. Intra-arterial vasodilators including verapamil and nitroglycerine were administered to prevent radial artery spasm. Next, we attempted to deliver the Terumo 6-Fr R2P Destination Slender 119 cm sheath for the interventional procedure. However, the sheath became stuck at the level of mid axillary artery due to severe radial artery spasm. Despite use of intra-arterial vasodilators, deep sedation with propofol, and gentle retraction, the sheath could not be removed and eventually broke requiring surgical removal. This case demonstrates severe radial artery spasm causing sheath entrapment that required emergency surgery for sheath removal. Unfortunately, the sheath could not be removed despite typical manoeuvres for severe spasm including intra-arterial vasodilators and deep sedation with propofol. Physicians performing PVIs via radial access need to be aware of this potentially serious complication.


The partition of nutrients between mother and conceptuses in the pregnant rat.
1. Diminishing the food supply to pregnant rats was associated with a subnormal degree of foetal loss among the larger litters, but a greatly lowered intake increased this foetal loss.2. Whether the food intake was lowered, normal or increased, the increase in conceptus weight over the last half of pregnancy could be related to the total maternal weight increase over this period by the formula y = (1/4)x + 4.5n, where n was the number of foetuses.3. With values of x below 20 g, this no longer held, but y never fell below 4.5 (n + 1).4. It is concluded that Hammond's theory of the partition of nutrients is confirmed, so far as mother and conceptuses are concerned, in the rat.


Human cytomegalovirus tegument protein pUL71 is required for efficient virion egress.
The human cytomegalovirus virion is composed of a DNA genome packaged in an icosahedral capsid, surrounded by a tegument of protein and RNA, all enclosed within a glycoprotein-studded envelope. Achieving this intricate virion architecture requires a coordinated process of assembly and egress. We show here that pUL71, a component of the virion tegument with a previously uncharacterized function, is required for the virus-induced reorganization of host cell membranes, which is necessary for efficient viral assembly and egress. A mutant that did not express pUL71 was able to efficiently accumulate viral genomes and proteins that were tested but was defective for the production and release of infectious virions. The protein localized to vesicular structures at the periphery of the viral assembly compartment, and during infection with a pUL71-deficient virus, these structures were grossly enlarged and aberrantly contained a cellular marker of late endosomes/lysosomes. Mutant virus preparations exhibited less infectivity per unit genome than wild-type virus preparations, due to aggregation of virus particles and their association with membrane fragments. Finally, mutant virus particles accumulated within the cytoplasm of infected cells and were localized to the periphery of large structures with properties of lysosomes, whose formation was kinetically favored in mutant-virus-infected cells. Together, these observations point to a role for pUL71 in the establishment and/or maintenance of a functional viral assembly compartment that is required for normal virion trafficking and egress from infected cells.


Retrospective Evaluation of Two-Implant-Supported Mandibular Overdentures with Radiographic and Clinical Aspects.
The aim of this retrospective study was to evaluate the clinical performance of two implants supporting mandibular overdentures by means of clinical and radiologic parameters, and also to explore the relationship of marginal bone loss with implant-/patient-related factors and soft tissue parameters. Data of patients who had undergone insertion of two implants into the interforaminal region between November 2012 and December 2016 using three different implant systems were retrieved from the archival records. Age, sex, implant length, implant diameter, observation period, mobility, and soft tissue parameters were recorded. Marginal bone levels and interimplant distances were measured with computer software on panoramic radiographs obtained at 3 months and at the recall session. A total of 43 patients with 86 implants were included in the study. Patients were evaluated with an average observation period of 41.79 months. Among the evaluated parameters, Gingival Index, Bleeding Index, and implant diameter were found to have significant effects on the marginal bone loss (P < .05). However, no significant effects of sex, age, implant length, observation period, and interimplant distance were observed on the marginal bone loss. No implants showed peri-implantitis or mobility, while eight implants showed peri-implant mucositis. Within the limitations of this study, it can be concluded that peri-implant soft tissue health and the diameter of the implant have an important effect on the marginal bone loss as well as the success of two-implant-supported mandibular overdentures.


[Idiopathic retroperitoneal fibrosis misdiagnosed as renal cancer: a case report and literature review].
A 51-year-old male patient was presented to our hospital for inspection of right renal space-occupying lesions. CT revealed soft tissue density in the right renal pelvis and renal pelvis ureter transitional crumb, for which a clinical diagnosis of right renal cancer was made. After laparoscopic radical resection of the right kidney, pathological examination supported the diagnosis of idiopathic retroperitoneal fibrosis. With an unclear pathogenesis, idiopathic retroperitoneal fibrosis presents with atypical clinical manifestations but shows specific features in imaging examination. Its treatment is individualized according to the specific condition for which conservative medical or surgical treatment can be considered. Retroperitoneal fibrosis has a low incidence and a high misdiagnosis rate, and imaging examinations remain currently the primary modality for diagnosis with specific findings.


[Study of immunogenicity and protective efficacy of a novel inactivated vaccine with chitosan against influenza A/H1N1/2009].
Study of immunogenicity and protective efficacy of a novel inactivated vaccine with chitosan against influenza A/H1N1/2009. Influenza virus A/California/7/2009 (H1N1) strain was used in the study. Mice were immunized twice (21 day interval) with experimental samples of inactivated influenza vaccine: No. 1--without the addition of chitosan, No. 2--with addition of chitosan. The blood was obtained 21 days after the first and 10 days after the second immunization with the vaccines and was treated with RDE. Antibody levels were evaluated in HI reaction. HI reaction method showed that antibody titers induced after immunization of vaccine No. 2 were higher than those induced after immunization with vaccine No. 1. Evaluation of protective efficacy of the vaccines against an experimental form of influenza infection in mice showed that after immunization with vaccine that does not contain chitosan the level of virus accumulation does not differ from the control statistically significantly (p < or = 0.05), at the same time the level of virus accumulation in the lungs of infected animals immunized with chitosan containing vaccine significantly (significantly with 95% probability) decreased by an average 3.01g when compared with control. Comparative analysis of immunogenicity and protective efficacy of experimental samples of inactivated influenza vaccine against influenza A/H 1N1/2009 showed that the vaccine with the addition of chitosan stimulates the formation of a higher immune response and promotes a more significant suppression of influenza A infectious agent reproduction in the lung target-organ.


[Experimental lung carcinogenic in vivo study of aflatoxin G1 in NIH mice].
Aflatoxin G1 (AFG1) is a member of the carcinogenic aflatoxin family produced by aspergillus flavus. It is a major contaminating mycotoxin in food in areas of China with high cancer incidence. The purpose of this study is to explore the carcinogenic effects of AFG1 in NIH mice. NIH mice were randomly divided into three groups. Two experimental groups were treated intragastrically by gavage with AFG1 3 microg/kg and AFG1 30 microg/kg respectively, 3 times a week for 24 weeks. The control group was treated with normal saline. All mice were fed with food that was free of AFGs as confirmed by HPLC analysis. The mice were weighed every week throughout the entire experiment, and then sacrificed and examined pathologically at the 58th and 74th weeks respectively. Compared with control mice receiving no AFG1, bronchial epithelial hyperplasia, alveolar hyperplasia and adenocarcinoma of lung were observed in mice receiving AFG1 treatment. The incidences of bronchial epithelial hyperplasia, alveolar hyperplasia and adenocarcinoma of lung were 60.0%, 10.0% and 30.0% for mice receiving 3 microg/kg AFG1 and 28.6%, 35.7%, 42.9% for mice receiving 30 microg/kg of the toxin, respectively. Oral administration of AFG1 can induce hyperplastic lesions and adenocarcinoma of lung in NIH mice.


Crohn disease: pathophysiology, diagnosis, and treatment.
Crohn disease (often seen in the literature as "Crohn's disease"), an autoimmune disease with debilitating gastrointestinal and extragastrointestinal manifestations, is on the rise in the United States and Europe. This article discusses the disease process, clinical presentation, diagnostic tools, and treatment options for Crohn disease. Statistics regarding disease prevalence and epidemiology also are reported.


Antibiotic-associated colitis.
We determined the incidence of antibiotic-associated colitis among users of oral antibiotics or topical clindamycin in a large prepaid health plan. Exposure to antibiotics was determined using a system that automatically records outpatient prescriptions filled and hospital diagnoses were available from computer files. Four cases of acute colitis were judged likely to be causally linked with outpatient use of antibiotics. These findings provide substantial evidence that antibiotic-associated colitis requiring hospital treatment occurs very rarely.


Employees' choice of a health plan and their subsequent satisfaction.
This article describes the reasons given by employees for choosing between an indemnification -type health insurance plan (Blue Cross/Blue Shield) and a health maintenance organization (group health plan). A population of 1,003 matched pairs was determined and questionnaires were sent to 1,861 individuals remaining in the company, with a response rate of 74%. Many of the reasons listed as important for joining one or the other plan were alike for both groups. However, the members of the group health plan felt that preventive care and regular checkups were more important than did the Blue Cross/Blue Shield members. The latter group felt that free choice of physician was very important, whereas the subscribers to the group health plan did not place such importance on this factor. Both groups were satisfied with their care, although there were some expected differences.


GeneAnalytics Pathway Analysis and Genetic Overlap among Autism Spectrum Disorder, Bipolar Disorder and Schizophrenia.
Bipolar disorder (BPD) and schizophrenia (SCH) show similar neuropsychiatric behavioral disturbances, including impaired social interaction and communication, seen in autism spectrum disorder (ASD) with multiple overlapping genetic and environmental influences implicated in risk and course of illness. GeneAnalytics software was used for pathway analysis and genetic profiling to characterize common susceptibility genes obtained from published lists for ASD (792 genes), BPD (290 genes) and SCH (560 genes). Rank scores were derived from the number and nature of overlapping genes, gene-disease association, tissue specificity and gene functions subdivided into categories (e.g., diseases, tissues or functional pathways). Twenty-three genes were common to all three disorders and mapped to nine biological Superpathways including Circadian entrainment (10 genes, score = 37.0), Amphetamine addiction (five genes, score = 24.2), and Sudden infant death syndrome (six genes, score = 24.1). Brain tissues included the medulla oblongata (11 genes, score = 2.1), thalamus (10 genes, score = 2.0) and hypothalamus (nine genes, score = 2.0) with six common genes (BDNF, DRD2, CHRNA7, HTR2A, SLC6A3, and TPH2). Overlapping genes impacted dopamine and serotonin homeostasis and signal transduction pathways, impacting mood, behavior and physical activity level. Converging effects on pathways governing circadian rhythms support a core etiological relationship between neuropsychiatric illnesses and sleep disruption with hypoxia and central brain stem dysfunction.


Cutaneous mucinosis of infancy: report of a rare case and review of the literature.
Cutaneous mucinosis of infancy (CMI) is a rare dermatologic condition, first reported in 1980 and currently classified within the complex group of papular mucinoses. We report a case of CMI and review the prior 13 cases in the literature. The patient was a 5-year-old girl who presented with asymptomatic dermal papules and plaques on her leg and back with no overlying color change. These lesions were first noticed during infancy and had become slightly more evident over time. The patient had a history of birthmarks and eczema. Her family history included eczema, allergies, photosensitivity, and Graves disease. Pre-biopsy clinical differential diagnosis included connective tissue nevus, granuloma annulare, myofibroma, lipofibroma, and lymphangioma. Biopsies revealed significant increase in interstitial mucin within the reticular and mid dermis, without significant sclerosis or fibroblastic proliferation. The relatively quiescent pattern of interstitial mucinosis with slight fibrocyte hyperplasia presenting as dermal papules-plaques on the trunk and extremities was most consistent with a diagnosis of CMI. We report another case of CMI in an otherwise healthy patient. Our patient is unique as she is the first CMI patient with a family history of Graves disease, although our patient appeared euthyroid. We will also review the literature on this rare entity.


A retrospective analysis of loss of reduction in operated supracondylar humerus fractures.
Loss of reduction following closed or open reduction of displaced supracondylar fractures of the humerus in children varies widely and is considered dependent on stability of the fracture pattern, Gartland type, number and configuration of pins for fixation, technical errors, adequacy of initial reduction, and timing of the surgery. This study was aimed to evaluate the factors responsible for failure of reduction in operated pediatric supracondylar fracture humerus. We retrospectively assessed loss of reduction by evaluating changes in Baumann's angle, change in lateral rotation percentage, and anterior humeral line in 77 consecutive children who were treated with multiple Kirschner wire fixation and were available for followup. The intraoperative radiographs were compared with those taken immediately after surgery and 3 weeks postoperatively. Multivariate logistic regression analysis was performed by STATA 10. Reduction was lost in 18.2% of the patients. Technical errors were significantly higher in those who lost reduction (P = 0.001; Odds Ratio: 57.63). Lateral pins had a significantly higher risk of losing reduction than cross pins (P = 0.029; Odds Ratio: 7.73). Other factors including stability of fracture configuration were not significantly different in the two groups. The stability of fracture fixation in supracondylar fractures in children is dependent on a technically good pinning. Cross pinning provides a more stable fixation than lateral entry pins. Fracture pattern and accuracy of reduction were not important factors in determining the stability of fixation.


Long-term antihypertensive therapy with guanfacine.
Twenty patients with essential hypertension were treated with guanfacine given in single 1-5 mg daily doses over a period of 24 weeks. Compared with the initial values at the end of the first washout period, there was a significant decrease in blood pressure and heart rate. The most common side effect, dryness of the mouth, usually disappeared after 8-10 weeks of treatment. No changes in laboratory values were seen. In the post-treatment placebo period there were significant increases in blood pressure and heart rate compared with the last readings during the treatment period. However, these never exceeded the pretreatment values. In a second series guanfacine (1-5 mg daily) was abruptly discontinued in 11 patients after 6-20 weeks of treatment. Blood pressure was measured twice a day, in lying and standing positions, during the 4 days preceding abrupt withdrawal of guanfacine and for 7 days after discontinuation. Clopamide was given concurrently to two patients, and this was continued after withdrawal of guanfacine. Only in two patients did the blood pressure rise to values above the initial levels (30 mmHg systolic and 10 diastolic), but no clinical symptoms were observed during the withdrawal. A transitory increase in heart rate between 10 and 30 bpm was observed in five patients after abrupt discontinuation of the drug.


"What is the impact of utilizing so-called best practices in percutaneous coronary intervention?": an interview with Atul Gupta.
Atul Gupta, MD speaks to Adam Price-Evans, Managing Commissioning Editor of Future Cardiology. Atul Gupta is the Global Chief Medical Officer for the business group Image Guided Therapy at Philips, providing medical guidance to Philips' clinical vision and strategy. As a practicing interventional and diagnostic radiologist, he also serves as a key external clinical voice for Image Guided Therapy. His key responsibilities include supporting innovation and product development in cardiology, peripheral vascular, surgical, oncology interventions, clinical education, office-based labs, medical affairs and new business development and ventures. He went to medical school and completed his postgraduate training in diagnostic radiology and a fellowship in interventional radiology. He maintains a clinical practice, performing interventional and diagnostic radiology in both hospital and office-based lab settings.


Unbalanced membrane phospholipid compositions affect transcriptional expression of certain regulatory genes in Escherichia coli.
The amount of porin protein OmpF in the outer membrane of Escherichia coli was reduced to one-third by the pgsA3 mutation that diminishes the amount of phosphatidylglycerol and cardiolipin in the membrane, whereas a cls (cardiolipin synthase) null mutation had no effect. Osmoregulation of OmpF was functional in the pgsA3 mutant. As assessed by the beta-galactosidase activities of lacZ fusions, the ompF expression was not reduced at the transcriptional level but was reduced about threefold at the posttranscriptional level by pgsA3. This reduction was mostly restored by a micF null mutation, and the micF RNA that inhibits the ompF mRNA translation was present 1.3 to 1.4 times more in the pgsA3 mutant, as assayed by RNase protection and Northern blot analyses. Elevation of the level of micF RNA was not restricted to acidic-phospholipid deficiency: OmpF was hardly detected and micF RNA was present 2.7 to 2.8 times more in a pssA null mutant that lacked phosphatidylethanolamine. Other common phenotypes of pgsA3 and pssA null mutants, reduced rates of cell growth and phospholipid synthesis, were not the cause of micF activation. Salicylate, which activates micF expression and inhibits cell motility, did not repress the flagellar master operon. These results imply that an unbalanced phospholipid composition, rather than a decrease or increase in the amount of specific phospholipid species, induces a phospholipid-specific stress signal to which certain regulatory genes respond positively or negatively according to their intrinsic mechanisms.


Abdominal adiposity largely explains associations between insulin resistance, hyperglycemia and subclinical atherosclerosis: the NEO study.
The relative importance of insulin resistance and hyperglycemia to the development of atherosclerosis remains unclear. Furthermore, adiposity may be responsible for observed associations. Our aim was to study the relative contributions of adiposity, insulin resistance and hyperglycemia to subclinical atherosclerosis. In this cross-sectional analysis of the Netherlands Epidemiology of Obesity (NEO) study, a cohort of persons of 45-65 years, BMI, waist circumference (WC), fasting glucose (FPG), HbA1c and insulin concentrations were measured and the revised HOMA-IR was calculated. The carotid Intima-Media Thickness (cIMT) was measured by ultrasound. We performed linear regression analyses between standardized values of FPG, HbA1c, HOMA-IR, BMI, WC with cIMT, and subsequently included age, sex, ethnicity, education and smoking, HOMA-IR, HbA1c and FPG, BMI and WC in the models. After exclusion of participants with glucose lowering therapy (n = 356) or missing data (n = 252), this analysis included 6065 participants, 43% men, and mean (SD) cIMT of 616 (92) μm. Differences in cIMT (95% CI) per SD were: FPG: 16 (10,21); HbA1c: 12 (7,16); HOMA-IR: 11 (6,16) μm. These associations attenuated after adjustments, and attenuated most strongly after adjustment for WC. Differences in cIMT (95% CI) per SD in the full model were: FPG: 4 (0,7); HbA1c: 2 (-1,5); HOMA-IR: 0 (-3,3); BMI 16 (13,19); WC: 18 (14,21) μm. In middle-aged individuals, we observed similar contributions of insulin resistance and hyperglycemia to subclinical atherosclerosis. These contributions were largely explained by abdominal adiposity, emphasizing the importance of weight management.


Arginine: mediator or modulator of sepsis?
Arginine is a conditionally essential amino acid that plays pivotal roles in maintaining body homeostasis. Arginine is a substrate for protein synthesis but can also be metabolized to various bioactive compounds that include nitric oxide, ornithine, polyamines, creatine phosphate, agmatine, and dimethylarginines. Arginine produces physiologic effects via nitric oxide dependent and independent pathways. Nitric oxide is important for the modulation of vascular tone, inflammation, immune function, endothelial function, platelet and leukocyte adherence, and neurotransmission. Nitric oxide modulates many biochemical processes important for the response to sepsis. Arginine, independent of nitric oxide, is important for growth, wound healing, cardiovascular function, immune function, inflammatory responses, energy metabolism, urea cycle function, and other metabolic processes. Arginine supplementation improves outcomes in animals with sepsis, wounds, ischemia-reperfusion injury, and following thermal injury. Enteral administration of arginine improves endothelial function but has little effect upon hemodynamics during human sepsis. An analysis of clinical studies using enteral formulas with supplemental arginine suggests benefits upon outcome, with no evidence of significant detrimental effects.


The structure and flexibility analysis of the Arabidopsis synaptotagmin 1 reveal the basis of its regulation at membrane contact sites.
Non-vesicular lipid transfer at ER and plasma membrane (PM) contact sites (CS) is crucial for the maintenance of membrane lipid homeostasis. Extended synaptotagmins (E-Syts) play a central role in this process as they act as molecular tethers of ER and PM and as lipid transfer proteins between these organelles. E-Syts are proteins constitutively anchored to the ER through an N-terminal hydrophobic segment and bind the PM via a variable number of C-terminal C2 domains. Synaptotagmins (SYTs) are the plant orthologous of E-Syts and regulate the ER-PM communication in response to abiotic stress. Combining different structural and biochemical techniques, we demonstrate that the binding of SYT1 to lipids occurs through a Ca2+-dependent lipid-binding site and by a site for phosphorylated forms of phosphatidylinositol, thus integrating two different molecular signals in response to stress. In addition, we show that SYT1 displays three highly flexible hinge points that provide conformational freedom to facilitate lipid extraction, protein loading, and subsequent transfer between PM and ER.


Presence of a p70 IL-2-binding peptide on leukemic cells from various hemopoietic lineages.
Recent studies have shown that IL-2R are composed of at least two polypeptide chains of 55 kDa (Tac or alpha-chain) and 70 to 75 kDa (p70 or beta-chain). The association of both chains forms high affinity IL-2R, whereas each chain alone binds IL-2 with a low (alpha-chain) or intermediate (beta-chain) affinity. So far, the p70 peptide has been found, in the absence of the Tac peptide, on the surface of lymphoid cells of T, B, or NK lineage. In this study, we investigated whether leukemic cells of various hemopoietic lineages expressed the p70 IL-2-binding protein. We found that both fresh leukemic cells obtained from patients, and cells from established leukemic lines of T cells, B cell, and myeloid origin constitutively expressed a p70 IL-2-binding protein on their surface, as detected by affinity cross-linking of radioiodinated IL-2. IL-2 binding and cross-linking to these cells was completely inhibited in the presence of an excess unlabeled rIL-2, but not with an anti-Tac mAb. Binding experiments on pre-B and myeloid cell lines revealed intermediate affinity IL-2R, whereas both high and intermediate affinity IL-2R were detected in T leukemic cells. The intermediate affinity binding of 125I-rIL-2 to the leukemic cell lines MOLT4 and Reh6 was inhibited by the TU27 mAb, which recognized the p75 chain of IL-2R. Moreover, the TU27 mAb could stain the K562, KM3, and MOLT4 (weakly) cell lines by indirect immunofluorescence. A high dose of rIL-2 (400 U/ml) enhanced the proliferation of cells from one out of three patients with acute myeloblastic leukemia, but it did not induce differentiation of the cells in any of three cases. Thus the finding of p70 IL-2-binding molecules on immature lymphoid and nonlymphoid hemopoietic cells should disclose new biologic functions for IL-2.


Cycle formation from acetylene addition on C4H3 radicals.
Various reactions following acetylene addition on i- and n-C(4)H(3) radicals are studied using a modified G3B3 method. For the addition of C(2)H(2) on n-C(4)H(3), the commonly admitted phenyl radical decomposition path of Madden and coworkers has been considered. In addition, several energetically competitive cyclisation steps are described for the first time. Data concerning addition to form non-cyclisable compounds are also provided. Addition on i-C(4)H(3) is extensively described including new cyclisation steps and hydrogen elimination reactions. The lowest energy path from n- or i-C(4)H(3) to a cyclic system goes through dehydro-fulvene radicals formation, which in the case of n-C(4)H(3) + C(2)H(2) is energetically competitive to the formation of the phenyl radical. Considering the degradation of the latter, the formation of 6-dehydrofulvene is energetically competitive as compared to the decomposition to ortho-benzyne + H, which is the assumed main degradation channel of the phenyl radical. Rate constants for all the steps considered in this work are obtained through the conventional transition state theory and provided at the end of the paper.


Heel pain in psoriatic arthropathy: Analysis of a series of 291 patients.
To determine the prevalence of heel pain in a series of patients with psoriatic arthritis (PsA). Cross-sectional, observational and retrospective study of a series of 347 patients. All patients fulfilled the CASPAR criteria for PsA and 291 had a clinically significant history of heel pain. The statistical analysis was performed using chi-square test, ANOVA and binary logistic regression. Thirty-five percent of the patients had clinically significant heel pain. A significant association was established between an early onset of skin and joint involvement in the disease and the development of heel pain. However, no significant correlation was found between disease duration and the presence of heel pain. History of dactylitis and PsA in first-degree family members was also statistically associated with this complication. Clinically significant heel pain was recorded in one third of the patients in this series. There was a statistically significant association with dactylitis, PsA in first-degree family members and an earlier onset of joint and skin disease.


Characterization of human MRP/Th RNA and its nuclear gene: full length MRP/Th RNA is an active endoribonuclease when assembled as an RNP.
Vertebrate cells contain a site-specific endoribonuclease (RNase MRP) that cleaves mitochondrial RNA transcribed from the origin of leading-strand mitochondrial DNA replication. This report presents the characterization of the human enzyme and its essential RNA component. Human RNase MRP is a ribonucleoprotein with a nucleus-encoded RNA of 265 nucleotides. As expected, the single-copy RNA coding region is homologous (84%) to the corresponding mouse gene; surprisingly, at least 700 nucleotides of the immediate 5'-flanking region are conserved. The 265-nucleotide MRP RNA and an MRP RNA cleavage product representing the 3'-terminal 108 nucleotides exist in nuclear and mitochondrial RNA isolates; the larger MRP RNA is present in greatest abundance in the nucleus. The putative processing site within the 265-nucleotide MRP RNA is offset from that of mouse MRP RNA, but in each case cleavage is precise and occurs at the sequence ANCCCGC. Oligonucleotide-mediated inhibition experiments reveal that both the 5' and 3' portions of the MRP RNA are involved in cleavage by RNase MRP; this implies that full length MRP RNA complexed with proteins is an active species in vertebrate cells.


Mental health promotion competencies in the health sector in Finland: a qualitative study of the views of professionals.
In this study, we aimed to investigate what competencies are needed for mental health promotion in health sector practice in Finland. A qualitative study was carried out to seek the views of mental health professionals regarding mental health promotion-related competencies. The data were collected via two focus groups and a questionnaire survey of professionals working in the health sector in Finland. The focus groups consisted of a total of 13 professionals. Further, 20 questionnaires were received from the questionnaire survey. The data were analysed using the qualitative data analysis software ATLAS.ti Scientific Software Development GmbH, Berlin. A content analysis was carried out. In total, 23 competencies were identified and clustered under the categories of theoretical knowledge, practical skills, and personal attitudes and values. In order to promote mental health, it is necessary to have a knowledge of the principles and concepts of mental health promotion, including methods and tools for effective practices. Furthermore, a variety of skills-based competencies such as communication and collaboration skills were described. Personal attitudes and values included a holistic approach and respect for human rights, among others. The study provides new information on what competencies are needed to plan, implement and evaluate mental health promotion in health sector practice, with the aim of contributing to a more effective workforce. The competencies provide aid in planning training programmes and qualifications, as well as job descriptions and roles in health sector workplaces related to mental health promotion.


Urologic consequences of myelodysplasia and other congenital abnormalities of the spinal cord.
Spina bifida and other congenital abnormalities of the spinal cord are relatively common (1 per 1000 births). Early urologic evaluation to determine the extent of neurologic involvement of the lower urinary tract is essential. Urodynamic studies are important in determining voiding pressure and leak pressure and in classifying the type of detrusor and sphincter dysfunction. Therapy is directed toward preservation of the upper tracts. Many nonsurgical (clean intermittent catheterization and anticholinergic drugs) and surgical procedures allow the child to be continent and maintain a normal upper urinary tract. The importance of follow-up is stressed because neurourologic changes frequently occur, and prompt treatment or change of therapy is essential. Today, children with spina bifida are leading healthy, productive lives. A continued multidisciplinary approach to their care is important.


Promoting ball skills in preschool-age girls.
Evidence supports that girls are less proficient than boys at performing ball skills. This study examined the immediate and long-term effects of a ball skill intervention on preschool-age girls' ball skill performance. Randomized controlled trial. Girls (Mage=47.24±7.38 months) were randomly assigned to a high autonomy, mastery-based 9-week motor skill intervention (the Children's Health Activity Motor Program; CHAMP, 540min; n=38) or a control group (free-play; n=16). Ball skill proficiency was assessed at pretest, posttest, and retention test (after 9 weeks) using the object control subscale of the Test of Gross Motor Development - 2nd Edition. Treatment efficacy was examined using linear mixed models. Two models were fit: one for short-term changes (pretest to posttest) and one for long-term changes (pretest to retention). Linear mixed models revealed a significantly time*treatment interaction for both models. Post hoc analysis confirmed that girls in CHAMP experienced significant gains in ball skills from pretest to posttest (p<.001) and pretest to retention (p<.001). Moreover, girls in CHAMP were no different from the control group at pretest (p>.05) but had significantly higher ball skills scores at both posttest (p<.001) and retention (p<.001). This study demonstrates the positive effects of a ball skill intervention (i.e., CHAMP) on improving girls' ball skills both short- and long-term. Findings suggest that early childhood interventions that focus on the development of ball skills in young girls might be an avenue to improve girls' ball skill performance.


Cumulative cultural learning: Development and diversity.
The complexity and variability of human culture is unmatched by any other species. Humans live in culturally constructed niches filled with artifacts, skills, beliefs, and practices that have been inherited, accumulated, and modified over generations. A causal account of the complexity of human culture must explain its distinguishing characteristics: It is cumulative and highly variable within and across populations. I propose that the psychological adaptations supporting cumulative cultural transmission are universal but are sufficiently flexible to support the acquisition of highly variable behavioral repertoires. This paper describes variation in the transmission practices (teaching) and acquisition strategies (imitation) that support cumulative cultural learning in childhood. Examining flexibility and variation in caregiver socialization and children's learning extends our understanding of evolution in living systems by providing insight into the psychological foundations of cumulative cultural transmission-the cornerstone of human cultural diversity.


Biochemical and immuno-pathological aspects of tissue transglutaminase in coeliac disease.
Tissue transglutaminase (tTg) has been identified as the major autoantigen in coeliac disease (CD). ELISA methods have been developed for measuring the autoantibody. There are divergent reports on the effects of calcium on the antibody binding to tTg. Furthermore, zinc is a potent inhibitor of tTg. To better understand the role of transglutaminase in CD, we have studied the stability of commercial tTG, the effect of CD serum on tTg-activity and the effects of calcium and zinc on the antibody binding. The inclusion of calcium during the coating of the ELISA plates significantly increases the binding of the antibody, while zinc at physiological concentrations inhibits the binding. Moreover, our results show that commercial guinea pig liver Tg treated with calcium contains at least four major antigenic molecules and is a labile enzyme, which is degraded rapidly by contaminating proteases. Human serum contains anti-proteases that protect the enzyme. Probably, the labile character of commercial tTG explains the divergent reports on the effects of calcium on antibody binding. Finally, antibodies in serum from a CD patient do not seem to inhibit tTg activity. Hypothetically, low, intestinal Zn2+ -levels facilitate Ca2+-activation of tTg, which deamidates gliadin. A complex between tTg and modified gliadin forms the antigen and triggers the immune reaction leading to manifest CD. Hypozincaemia secondary to villous atrophy aggravates the induced disease.


Prognosis patients with COVID-19 using deep learning.
The coronavirus (COVID-19) is a novel pandemic and recently we do not have enough knowledge about the virus behaviour and key performance indicators (KPIs) to assess the mortality risk forecast. However, using a lot of complex and expensive biomarkers could be impossible for many low budget hospitals. Timely identification of the risk of mortality of COVID-19 patients (RMCPs) is essential to improve hospitals' management systems and resource allocation standards. For the mortality risk prediction, this research work proposes a COVID-19 mortality risk calculator based on a deep learning (DL) model and based on a dataset provided by the HM Hospitals Madrid, Spain. A pre-processing strategy for unbalanced classes and feature selection is proposed. To evaluate the proposed methods, an over-sampling Synthetic Minority TEchnique (SMOTE) and data imputation approaches are introduced which is based on the K-nearest neighbour. A total of 1,503 seriously ill COVID-19 patients having a median age of 70 years old are comprised in the research work, with 927 (61.7%) males and 576 (38.3%) females. A total of 48 features are considered to evaluate the proposed method, and the following results are achieved. It includes the following values i.e., area under the curve (AUC) 0.93, F2 score 0.93, recall 1.00, accuracy, 0.95, precision 0.91, specificity 0.9279 and maximum probability of correct decision (MPCD) 0.93. The results show that the proposed method is significantly best for the mortality risk prediction of patients with COVID-19 infection. The MPCD score shows that the proposed DL outperforms on every dataset when evaluating even with an over-sampling technique. The benefits of the data imputation algorithm for unavailable biomarker data are also evaluated. Based on the results, the proposed scheme could be an appropriate tool for critically ill Covid-19 patients to assess the risk of mortality and prognosis.


Anti-atherosclerotic effect of atorvastatin and clopidogrel alone and in combination in rats.
Atherosclerosis is a disease affecting arterial blood vessels due to the accumulation of macrophage white blood cells and low density lipoproteins. Effects of atorvastatin, a recently introduced lipid lowering statin was studied alone and in combination with clopidogrel in high fat diet fed atherosclerotic rats orally. Results showed significant reduction in total serum cholesterol and malondialdehyde levels and significant improvement in urine creatinine levels. Aortic cross sections of rats treated with clopidogrel alone showed reversal of atherosclerotic calcification. The same effect was observed with the combined treatment of clopidogrel and atorvastatin. Only atorvastatin treatment did not show any histological atheroprotective effect. Atorvastatin and clopidogrel alone and in combination have offered significant atheroprotective effect. No specific advantage was seen with combined treatment of atorvastatin and clopidogrel, moreover the advantages seen with independent drug administration also reduced with combined treatment.


Molecular characterization of hepatitis B virus in blood donors from Burkina Faso: Prevalence of quasi-subgenotype A3, genotype E, and mixed infections.
Burkina Faso is a highly endemic area for Hepatitis B virus (HBV) which remains a major challenge for blood safety with >13% of candidate blood donors being chronically infected. However, little is known about the molecular epidemiology of the viral strains currently circulating. In this study, 99 HBV strains from HBsAg positive candidate blood donors in Ougadougou were genetically characterized by sequencing the pre-S/S region of the viral genome. Phylogenetic analyses revealed a 25% prevalence of HBV quasi-subgenotype A3 (A3QS ) co-circulating with the confirmed dominant HBV genotype E (72%). HBV/A3QS sequences formed a sub-cluster closely related to West-African sequences previously characterized, and showed a low intra-group genetic diversity (0.75%) suggesting a relatively recent spreading of HBV/A3QS strains in Burkina Faso. Low genetic diversity of genotype E strains compared to A3QS was confirmed. Mixed infections with the two genotypes were identified in 3% of the donors tested and contributed to artifacts during PCR amplification of the viral genome leading to erroneous apparent intergenotype recombinant sequences. While the co-circulation of two HBV genotypes in a restricted area may favor the emergence of intergenotype recombinant variants, strictly controlled molecular experimental procedures should be used to accurately characterize HBV circulating recombinant forms. J. Med. Virol. 88:2145-2156, 2016. © 2016 Wiley Periodicals, Inc.


Comparisons of nomograms and urologists' predictions in prostate cancer.
When applying nomograms to a clinical setting it is essential to know how their predictions compare with clinicians'. Comparisons exist outside of the prostate cancer literature. We reviewed these comparisons and conducted 2 experiments comparing predictions of clinicians with prostate cancer nomograms. By using Medline, we searched studies from January 1966 to July 1999 that compared human predictions with nomogram predictions. Next, we conducted 2 experiments: (1) 17 urologists were presented with 10 case vignettes and asked to predict the 5-year recurrence-free probabilities for each patient; (2) case presentations of 63 prostate cancer patients (including full clinical histories with complete diagnostic data and surgical findings) were made to a group of 25 clinicians who were asked to predict organ-confined disease. We found 22 published studies comparing human experts with nomograms, greater than half (13 of 22) showed the nomogram performing above the level of the human expert. Our first experiment showed urologist modification of 165 nomogram predictions led to a decrease in prediction accuracy (c-index decreased from.67 to.55, P <.05). In our second experiment, clinician predictions of organ-confined disease were comparable to the nomogram (area under the receiver operating characteristic curve [AUC] 0.78 and 0.79, respectively). A mixed-model suggests the nomogram did not augment clinician prediction accuracy (doctor excess error 1.4%, P =.75, 95% confidence interval [CI]: -10.9% to 8.2%). Our data suggest that nomograms do not seem to diminish predictive accuracy and they may be of significant benefit in certain clinical decision making settings.


Magnetically induced muscle contraction is caused by motor nerve stimulation and not by direct muscle activation.
When magnetically stimulating peripheral nerves, a local cocontraction of muscle under the coil is observed. We assessed whether this contraction results from: (1) magnetic stimulation of motor nerves, or (2) direct depolarization of the muscle membrane. Wrist extensor muscles of normal subjects were magnetically stimulated with the coil placed directly above the muscle. Neuromuscular transmission was then blocked by atracurium using a technique of local curarization. As a reference, the radial nerve was stimulated electrically. Magnetic and electrical stimuli were applied alternatingly every 10 s. Twitch force of wrist extension was measured isometrically over a period of about 70 min including the phase of complete neuromuscular block. Twitch amplitudes elicited by magnetic and electrical stimuli were equivalent during the whole experiment. These results suggest that muscle cocontraction following magnetic stimulation results from depolarization of terminal motor nerve branches.


Time trends of nasopharyngeal carcinoma in urban Guangzhou over a 12-year period (2000-2011): declines in both incidence and mortality.
Nasopharyngeal carcinoma (NPC) is an uncommon disease in most countries but occurs with much greater frequency in southern China. This study aimed to examine the secular trends of NPC in urban Guangzhou over the time period of 2000-2011 using data from the Guangzhou Cancer Registry. Age-adjusted annual incidence rates of NPC were calculated by the direct method using the WHO World Standard Population (1960) as the reference. The average annual percentage change (AAPC) was used as an estimate of the trend. A total of 7,532 new cases of NPC and 3,449 related deaths were registered. In both genders, the peak incidence occurred in the 50- to 59-year age group, and this age distribution pattern remained similar throughout. The AAPC in NPC incidence rates was -3.26% (95% CI: -5.4%--1.1) for males and -5.74% (95% CI: -8.9%--2.5) for females, resulting in a total decrease of 39.3% (from 22.14 to 13.44 per 100,000 population) for males and 48.6% (from 10.1 to 5.18 per 100,000 population) for females over this 12-year period. The AAPCs in NPC mortality rates were -4.62% (95%CI: -3.5%--5.7) for males and -6.75% (95% CI: -5.2%--8.3) for females, resulting in a total decrease of -46.1% (from 12.1 to 6.54 per 100,000 population) for males and 51.7% (from 4.14 to 2.00 per 100,000 population) for females. The age-adjusted incidence and mortality rates of NPC declined during 2000-2011 in urban Guangzhou but remained high. Future efforts to improve prevention, early detection and treatment strategies are needed.


Canal of nuck hernia with uterus and ovary presenting as inguinal swelling in a female infant.
Canal of nuck hernia is rarely reported in pediatric population. We report one such case of a canal of nuck hernia in a 2-month-old girl containing uterus, ovary and small bowel diagnosed on ultrasonography, and which was later confirmed and treated surgically.


Effect of vasoactive peptides in Tetrahymena: chemotactic activities of adrenomedullin, proadrenomedullin N-terminal 20 peptide (PAMP) and calcitonin gene-related peptide (CGRP).
Adrenomedullin (AMD), proadrenomedullin N-terminal 20 peptide (PAMP) and calcitonin gene-related peptide (CGRP) were studied for chemotaxis, chemotactic selection and G-actin/F-actin transition in Tetrahymena. The aim of the experiments was to study the effects of two different peptides encoded by the same gene compared to a peptide related to one of the two, but encoded by a different gene, at a low level of phylogeny. The positive, chemotactic effect of ADM and the strong negative, chemorepellent effect of PAMP suggest that in Tetrahymena, the two peptides elicit their chemotactic effects via different signalling mechanisms. The complexity of swimming behaviour modulated by the three peptides underlines that chemotaxis, chemokinesis and some characteristics of migratory behaviour (velocity, tortuosity) are working as a sub-population level complex functional unit. Chemotactic responsiveness to ADM and CGRP is short-term, in contrast to PAMP, which as a chemorepellent ligand, has the ability to select sub-populations with negative chemotactic responsiveness. The different effects of ADM and PAMP on the polymerization of actin networks show that the microtubular structure of cilia is more essential to chemotactic response than are transitions of the actin network. The results draw attention to the characteristic effects of vasoactive peptides at this low level of phylogeny.


Interleukin-3 (IL-3)-induced c-fos activation is modulated by Gab2-calcineurin interaction.
Interleukin-3 (IL-3) regulates cell growth by affecting various processes such as cell death, survival, and proliferation. Cues from the external environment are sensed by surface receptors, and complex signaling mechanisms arise within the cells, leading to specific functional outcomes. In this study, we demonstrate that the cytokine IL-3 induces the activation of the Ca(2+)-dependent phosphatase, calcineurin (Cn). Furthermore Cn dephosphorylates Gab2, resulting in c-fos activation and cell proliferation. We also report that there is a direct interaction between Cn and Gab2 upon IL-3 stimulation, and Akt can regulate this interaction.


Gene expression changes during mouse skeletal myoblast differentiation revealed by transcriptional profiling.
Studies described here utilize high-density oligonucleotide arrays to characterize changes in global mRNA expression patterns during proliferation, cell cycle withdrawal, and terminal differentiation in mouse C2C12 myoblasts. Statistical analyses revealed 629 sequences differentially regulated between proliferating and differentiating myoblasts. These genes were clustered using self-organizing maps to identify sets of coregulated genes and were assigned to functional categories that were analyzed for distribution across expression clusters. Clusters were identified with statistically significant enrichment of functional categories including muscle contraction, cell adhesion, extracellular matrix function, cellular metabolism, mitochondrial transport, DNA replication, cell cycle control, mRNA transcription, and unexpectedly, immune regulation. In addition, functional category enrichment data can be used to predict gene function for numerous differentially regulated expressed sequence tags. The results provide new insight into how genes involved in these cellular processes may play a role in skeletal muscle growth and differentiation.


Effect of milk thistle on the pharmacokinetics of indinavir in healthy volunteers.
To characterize the pharmacokinetics of indinavir in the presence and absence of milk thistle and to determine the offset of any effect of milk thistle on indinavir disposition. Prospective open-label drug interaction study. Outpatient clinic. Ten healthy volunteers. Intervention. Blood samples were collected over 8 hours after the volunteers took four doses of indinavir 800 mg every 8 hours on an empty stomach for baseline pharmacokinetics. This dosing and sampling were repeated after the subjects took milk thistle 175 mg (confirmed to contain silymarin 153 mg, the active ingredient) 3 times/day for 3 weeks. After an 11-day washout, indinavir dosing and blood sampling were repeated to evaluate the offset of any potential interaction. Indinavir concentrations were measured by using a validated high-performance liquid chromatography method. The following pharmacokinetic parameters were determined: highest concentration (Cmax), hour-0 concentration, hour-8 concentration (C8), time to reach Cmax, and area under the plasma concentration-time curve over the 8-hour dosing interval (AUC8). Milk thistle did not alter significantly the overall exposure of indinavir, as evidenced by a 9% reduction in the indinavir AUC8 after 3 weeks of dosing with milk thistle, although the least squares mean trough level (C8) was significantly decreased by 25%. Milk thistle in commonly administered dosages should not interfere with indinavir therapy in patients infected with the human immunodeficiency virus.


Detection, molecular characterization, and antibiogram of multi-drug resistant and methicillin-resistant Staphylococcus aureus (MRSA) isolated from pets and pet owners in Malaysia.
The emergence of multidrug-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Staphylococcus aureus (MDRSA) in animals and humans with continuous contact are a great zoonotic concern. This cross-sectional study was performed to investigate the carriage rate, genotypic characteristics, and to determine the antibiogram of S. aureus isolated from pets and pet owners in Malaysia. Nasal and oral swab samples from 40 cats, 30 dogs, and 70 pet owners were collected through convenient sampling. Presumptive colonies on mannitol salt agar were subjected to biochemical identification. S. aureus and MRSA were confirmed by PCR detection of nuc and mecA genes, respectively. Molecular profiles for antimicrobial resistance and virulence genes in S. aureus were also determined. The antibiogram was carried out via Kirby-Bauer test using 18 antibiotics. 17.5% of cats, 20% of dogs, and 27% of pet owners were S. aureus positive. MRSA was also detected in dogs, and pet owners. S. aureus isolates displayed high resistance against penicillin (72.7%), and amoxicillin/clavulanate (66.7%). 39.4% of S. aureus isolates showed multidrug-resistance traits, phenotypically. Molecular characterization of S. aureus revealed the presence of mecA, tetk, tetL, ermA, ermB, ermC, msrA, scn, chp, sak, sep, and sea genes. This study showed the emergence of MRSA and MDRSA in pets and pet owners in Malaysia. The antibiogram findings showed resistance of S. aureus to multiple antibiotics. Furthermore, molecular analysis of immune evasion cluster (IEC) strongly suggests the spread of animal-adapted S. aureus lineages among pets and pet owners.


Phosphodiesterase inhibition and theophylline.
Purification of cyclic nucleotide phosphodiesterases from human lung tissue and the characteristics of the purified enzymes are briefly summarized. The relation between the capacity of theophylline to inhibit cyclic AMP phosphodiesterase activity and its bronchodilating properties is discussed.


Recurrent ovarian carcinoma presenting as a solitary metastasis to the kidney.
Unusual sites for recurrent ovarian metastases include extrahepatic solid organs (except the spleen), bone and the abdominal wall. We report a rare renal recurrence of ovarian malignancy and its imaging features.


Molecular epidemiology of enterococci with high-level resistance to aminoglycosides.
DNA-based methodologies are considerably more powerful than other phenotype-based typing systems, providing a finer level of epidemiological discrimination, differentiating both closely and distantly related independent isolates that otherwise may appear as identical. In this study, plasmid analysis and pulsed-field gel electrophoresis were used to compare 28 isolates of Enterococci (respectively 13 strains of Enterococcus faecalis and 15 strains of Enterococcus faecium) with high-level resistance to aminoglycosides, isolated in Catania (Italy). Plasmid profile analysis resolved 20 different patterns among 24 plasmid harboring strains; many isolates showed one or two plasmids of the same size, but different plasmid content. Analysis of the PFGE-based RFLP patterns after SmaI digestion of genomic DNA resolved 26 different clones from 28 isolates: particularly, it resolved two different clones from three isolates showing identical plasmid profiles, and it identified as a single clone two isolates exhibiting different plasmid profiles. Thus, on the basis of our PFGE-based RFLP analysis data, we concluded that all the strains included in the study were genetically unrelated with two exceptions.


Premotor activations in response to visually presented single letters depend on the hand used to write: a study on left-handers.
In a previous fMRI study on right-handers (Rhrs), we reported that part of the left ventral premotor cortex (BA6) was activated when alphabetical characters were passively observed and that the same region was also involved in handwriting [Longcamp, M., Anton, J. L., Roth, M., & Velay, J. L. (2003). Visual presentation of single letters activates a premotor area involved in writing. NeuroImage, 19, 1492-1500]. We therefore suggested that letter-viewing may induce automatic involvement of handwriting movements. In the present study, in order to confirm this hypothesis, we carried out a similar fMRI experiment on a group of left-handed subjects (Lhrs). We reasoned that if the above assumption was correct, visual perception of letters by Lhrs might automatically activate cortical motor areas coding for left-handed writing movements, i.e., areas located in the right hemisphere. The visual stimuli used here were either single letters, single pseudoletters, or a control stimulus. The subjects were asked to watch these stimuli attentively, and no response was required. The results showed that a ventral premotor cortical area (BA6) in the right hemisphere was specifically activated when Lhrs looked at letters and not at pseudoletters. This right area was symmetrically located with respect to the left one activated under the same circumstances in Rhrs. This finding supports the hypothesis that visual perception of written language evokes covert motor processes. In addition, a bilateral area, also located in the premotor cortex (BA6), but more ventrally and medially, was found to be activated in response to both letters and pseudoletters. This premotor region, which was not activated correspondingly in Rhrs, might be involved in the processing of graphic stimuli, whatever their degree of familiarity.


Desiccation and freezing tolerance of embryonic axes from Citrus sinensis [L.] osb. pretreated with sucrose.
Embryonic axes of Citrus sinensis L. were successfully cryopreserved. While fully hydrated unfrozen axes germinated 100%, survival decreased as axes water content dropped, and total loss of viability was observed when the water content dropped to 0.04 and 0.10 mg H2O/mg dry mass, for axes without and with sucrose preculture, respectively. Fully hydrated axes did not survive exposure to liquid nitrogen. Highest seedling recovery (93-100%) for untreated axes was observed at 0.26 to 0.15 mg H2O/mg dry mass. Differential scanning calorimetry revealed the presence of broad melting peaks in fully hydrated embryonic axes. The size of the melting peak diminished as water was removed by desiccation. Minimum melting of water was observed at the point axes survived cryopreservation. Occurrence of a glass transition upon warming was not a condition for axes to survive liquid nitrogen exposure. In untreated axes, glucose, increased with desiccation to 0.2 mg H2O/mg dry mass, and decreased as the axes were desiccated to lower water contents. Fructose and sucrose levels did not increase when untreated samples were desiccated for the same periods of time. Raffinose and stachyose levels decreased as untreated and precultured embryonic axes were desiccated. In sucrose precultured axes, sucrose and fructose levels increased when they were dehydrated, reaching maximum levels at 0.2 mg H2O/mg dry mass. Tissue glucose did not change significantly with desiccation. Raffinose and stachyose levels dropped as precultured embryonic axes were dried.


Recommendations on the Use of Ultrasound Guidance for Adult Thoracentesis: A Position Statement of the Society of Hospital Medicine.
Executive Summary: 1) We recommend that ultrasound should be used to guide thoracentesis to reduce the risk of complications, the most common being pneumothorax. 2) We recommend that ultrasound guidance should be used to increase the success rate of thoracentesis. 3) We recommend that ultrasound-guided thoracentesis should be performed or closely supervised by experienced operators. 4) We suggest that ultrasound guidance be used to reduce the risk of complications from thoracentesis in mechanically ventilated patients. 5) We recommend that ultrasound should be used to identify the chest wall, pleura, diaphragm, lung, and subdiaphragmatic organs throughout the respiratory cycle before selecting a needle insertion site. 6) We recommend that ultrasound should be used to detect the presence or absence of an effusion and approximate the volume of pleural fluid to guide clinical decision-making. 7) We recommend that ultrasound should be used to detect complex sonographic features, such as septations, to guide clinical decision-making regarding the timing and method of pleural drainage. 8) We suggest that ultrasound be used to measure the depth from the skin surface to the parietal pleura to help select an appropriate length needle and determine the maximum needle insertion depth. 9) We suggest that ultrasound be used to evaluate normal lung sliding pre- and postprocedure to rule out pneumothorax. 10) We suggest avoiding delay or interval change in patient position from the time of marking the needle insertion site to performing the thoracentesis. 11) We recommend against performing routine postprocedure chest radiographs in patients who have undergone thoracentesis successfully with ultrasound guidance and are asymptomatic with normal lung sliding postprocedure. 12) We recommend that novices who use ultrasound guidance for thoracentesis should receive focused training in lung and pleural ultrasonography and hands-on practice in procedural technique. 13) We suggest that novices undergo simulation-based training prior to performing ultrasound-guided thoracentesis on patients. 14) Learning curves for novices to become competent in lung ultrasound and ultrasound-guided thoracentesis are not completely understood, and we recommend that training should be tailored to the skill acquisition of the learner and the resources of the institution.


Effect of extreme data loss on long-range correlated and anticorrelated signals quantified by detrended fluctuation analysis.
Detrended fluctuation analysis (DFA) is an improved method of classical fluctuation analysis for nonstationary signals where embedded polynomial trends mask the intrinsic correlation properties of the fluctuations. To better identify the intrinsic correlation properties of real-world signals where a large amount of data is missing or removed due to artifacts, we investigate how extreme data loss affects the scaling behavior of long-range power-law correlated and anticorrelated signals. We introduce a segmentation approach to generate surrogate signals by randomly removing data segments from stationary signals with different types of long-range correlations. The surrogate signals we generate are characterized by four parameters: (i) the DFA scaling exponent alpha of the original correlated signal u(i) , (ii) the percentage p of the data removed from u(i) , (iii) the average length mu of the removed (or remaining) data segments, and (iv) the functional form P(l) of the distribution of the length l of the removed (or remaining) data segments. We find that the global scaling exponent of positively correlated signals remains practically unchanged even for extreme data loss of up to 90%. In contrast, the global scaling of anticorrelated signals changes to uncorrelated behavior even when a very small fraction of the data is lost. These observations are confirmed on two examples of real-world signals: human gait and commodity price fluctuations. We further systematically study the local scaling behavior of surrogate signals with missing data to reveal subtle deviations across scales. We find that for anticorrelated signals even 10% of data loss leads to significant monotonic deviations in the local scaling at large scales from the original anticorrelated to uncorrelated behavior. In contrast, positively correlated signals show no observable changes in the local scaling for up to 65% of data loss, while for larger percentage of data loss, the local scaling shows overestimated regions (with higher local exponent) at small scales, followed by underestimated regions (with lower local exponent) at large scales. Finally, we investigate how the scaling is affected by the average length, probability distribution, and percentage of the remaining data segments in comparison to the removed segments. We find that the average length mu_{r} of the remaining segments is the key parameter which determines the scales at which the local scaling exponent has a maximum deviation from its original value. Interestingly, the scales where the maximum deviation occurs follow a power-law relationship with mu_{r} . Whereas the percentage of data loss determines the extent of the deviation. The results presented in this paper are useful to correctly interpret the scaling properties obtained from signals with extreme data loss.


[Biomechanical investigations of the liver capsule (author's transl)].
The strain properties of geometrically defined specimens of human, pig, and bovine liver capsule were analysed in vitro by applying histomechanical procedures. The dynamic relaxation correlates with the static relaxation under sinus shaped strain process after previous additional predetermined increase in length. If such a process occurs in the linear region of the stress-strain curve, the relaxation process continues on a new level even if the amplitude of the sinus length-time input function is augmented. The same experiment causes in the lower non-linear region of the stress-strain relation the so-called asymmetric amplitude phenomenon. Further histomechanical features of the liver capsule obtained after defined length-time input functions such as relaxation, static isorheological line, dynamic isorheological curve, increase of the vertices of the dynamic force-time function after static relaxation and dynamic force recovery curve are shown. The phase shift between force and lenth is pointed out. The significance of the biomechanical properties of the liver capsule under physiological and pathological conditions is discussed.


Why do patients choose self-care dialysis?
Self-care dialysis (SCD) is associated with cost savings and possibly improved quality of life compared to in-centre haemodialysis. Despite this, less than one in four dialysis patients are currently treated with SCD. Our objectives were to identify perceived advantages of SCD associated with increased odds of selecting SCD, and to evaluate the effect of an educational intervention on patients' perceptions of these advantages. We randomized patients with GFR<30 ml/min to standard pre-dialysis education or a multifaceted educational intervention. After each component of the intervention, participants completed a questionnaire on which they identified advantages of SCD and indicated their preferred dialysis modality. We used inductive coding to identify perceived advantages of SCD. Seventy patients participated in the study. We identified three advantages of SCD: freedom, lifestyle and control. Of these, freedom and lifestyle were associated with increased odds of selecting SCD [OR 9.1 (2.0, 41.3) and 7.0 (1.6, 29.7), respectively]. We combined these advantages for receiver-operating characteristic (ROC) analysis to assess accuracy in predicting patients' intended choice of dialysis. The area under the ROC curve was 0.82 (0.70, 0.93). Patients who received the educational intervention were more likely to perceive freedom and control as advantages, and were less likely to identify no advantages of SCD. Patients who identify freedom and lifestyle advantages of SCD are more likely to choose SCD. Providing additional education on dialysis modalities increases patients' perceptions of the advantages of SCD and the odds of them selecting SCD.


Docking of human interleukin-15 to its specific receptor alpha chain: correlation between molecular modeling and mutagenesis experimental data.
A structural model of the sushi domain of IL-15Ralpha was first obtained by homology modeling to study its interactions with IL-15 by means of molecular modeling, peptide scanning, and site-directed mutagenesis. From these experimental data, a putative interacting surface of IL-15Ralpha with a previously published IL-15 model was inferred: Leu25, Leu44, and Glu46 of IL-15 and Arg35 of IL-15Ralpha were found to be key interfacial residues and were subsequently used as filters for the construction of docking solutions. Human IL-15/IL-15Ralpha complexes were constructed in two stages, with a preliminary docking procedure, treating the two partners as rigid bodies and using these filters. In this first stage, two classes of docking solutions were characterized. From a topological point of view, each solution could be derived from the other by reverse orientation of one partner in relation to the other. In a second stage, several further energy refinements clearly favored one solution. Moreover, this unique docking solution was confirmed by molecular modeling of IL-15 mutants previously built and tested in our laboratory. Finally, this complex model, which is a useful tool to study the IL-15/IL-15Ralpha interface, was topologically compared to IL-2/IL-2Ralpha complexes (previous model in the literature and recent crystal structure).


Spinal Epidural Hematoma Due To Tyre-Blast Injury: A Case Report.
A retrospective case report. The objective of this article is to report a spinal epidural hematoma (SEH) due to shock wave. SEH is an infrequent condition. Most of SEH's are spontaneous. We have reported an SEH traumatic case without bone lesions due to exploding truck tire. A different category of blast injuries is the one related with exploding tyres. Shock waves are the main mechanism that is responsible for blast injuries. We are presenting the first report of acute SEH due to shock wave. A 33-year-old man was brought to the emergency department with complaints of weakness and numbness of the upper extremities. There was an epidural high-signal density without osseous lesion in computerized tomography from the level of C2 to C5, and there was a T2-weighted hyperintense lesion in magnetic resonance imaging from the level of C2 to C5 with compression of the spinal cord the anterior and posterior which proved to be an SEH. The patient was discharged from the hospital with complete neurologic recovery. SEH should be considered possible in the blast injury. SEH condition carries a significant risk of morbidity and mortality without early recognition and rapid management. 5.


Cloning and expression of cDNA for human poly(ADP-ribose) polymerase.
cDNAs encoding poly(ADP-ribose) polymerase from a human hepatoma lambda gt11 cDNA library were isolated by immunological screening. One insert of 1.3 kilobases (kb) consistently hybridized on RNA gel blots to an mRNA species of 3.6-3.7 kb, which is consistent with the size of RNA necessary to code for the polymerase protein (116 kDa). This insert was subsequently used in both in vitro hybrid selection and hybrid-arrested translation studies. An mRNA species from HeLa cells of 3.6-3.7 kb was selected that was translated into a 116-kDa protein, which was selectively immunoprecipitated with anti-poly (ADP-ribose) polymerase. To confirm that the 1.3-kb insert from lambda gt11 encodes for poly(ADP-ribose) polymerase, the insert was used to screen a 3- to 4-kb subset of a transformed human fibroblast cDNA library in the Okayama-Berg vector. One of these vectors [pcD-p(ADPR)P; 3.6 kb] was tested in transient transfection experiments in COS cells. This cDNA insert contained the complete coding sequence for polymerase as indicated by the following criteria: A 3-fold increase in in vitro activity was noted in extracts from transfected cells compared to mock or pSV2-CAT transfected cells. A 6-fold increase in polymerase activity in pcD-p(ADPR)P transfected cell extracts compared to controls was observed by "activity gel" analysis on gels of electrophoretically separated proteins at 116 kDa. A 10- to 15-fold increase in newly synthesized polymerase was detected by immunoprecipitation of labeled transfected cell extracts. Using pcD-p(ADPR)P as probe, it was observed that the level of poly(ADP-ribose) polymerase mRNA was elevated at 5 and 7 hr of S phase of the HeLa cell cycle, but was unaltered when artificial DNA strand breaks are introduced in HeLa cells by alkylating agents.


Investigating high school students' conceptualizations of the biological basis of learning.
Students go to school to learn. How much, however, do students understand about the biological basis of this everyday process? Blackwell et al. (1) demonstrated a correlation between education about learning and academic achievement. Yet there are few studies investigating high school students' conceptions of learning. In this mixed-methods research study, written assessments were administered to 339 high school students in an urban school district after they completed their required biology education, and videotaped interviews were conducted with 15 students. The results indicated that the majority of students know little about the biological basis of learning, even with prompting, and they recall having learned little about it in school. Students appear to believe that people control their own ability to learn, and some have developed personal hypotheses to describe the learning process. On written assessments, 75% of participants demonstrated a nonbiological framework for learning, and, during interviews, 67% of participants revealed misconceptions about the biological basis of learning. Sample quotes of these interviews are included in this report, and the implications of these findings are discussed.


Diverticular disease of the large bowel in Singapore. An autopsy survey.
One thousand fourteen consecutive large intestines were removed at autopsy from persons over the age of 14 years and examined for diverticular disease. Diverticulosis was encountered in 194 patients (19 percent). The lesion appeared early in life, after the second decade. Men were affected more frequently than women before the age of 60 years. Chinese men had significantly more diverticular disease than Malayan men (P less than 0.01) and Indian men (P less than 0.02). Chinese men also had significantly more diverticular disease than Chinese women. There was a predominance of right colon involvement, with the disease affecting especially the ascending colon and cecum. This pattern was observed in all three major ethnic groups, and in both the Singapore-born and foreign-born Singaporeans. The cause of right-sided diverticulosis is unknown. It appears that, while adoption of the western diet may influence the prevalence of diverticular disease, the site of predilection is determined more by racial or genetic predisposition. All diverticula examined histologically were false, including 39 (20 percent) solitary diverticula. The distribution of solitary diverticula was similar to that of multiple diverticulosis. It is suggested that solitary and multiple diverticulosis are part of the spectrum of the same disease.


Lateral Ramus Cortical Bone Plate in Alveolar Cleft Osteoplasty with Concomitant Use of Buccal Fat Pad Derived Cells and Autogenous Bone: Phase I Clinical Trial.
Tissue regeneration has become a promising treatment for craniomaxillofacial bone defects such as alveolar clefts. This study sought to assess the efficacy of lateral ramus cortical plate with buccal fat pad derived mesenchymal stem cells (BFSCs) in treatment of human alveolar cleft defects. Ten patients with unilateral anterior maxillary cleft met the inclusion criteria and were assigned to three treatment groups. First group was treated with anterior iliac crest (AIC) bone and a collagen membrane (AIC group), the second group was treated with lateral ramus cortical bone plate (LRCP) with BFSCs mounted on a natural bovine bone mineral (LRCP+BFSC), and the third group was treated with AIC bone, BFSCs cultured on natural bovine bone mineral, and a collagen membrane (AIC+BFSC). The amount of regenerated bone was measured using cone beam computed tomography 6 months postoperatively. AIC group showed the least amount of new bone formation (70 ± 10.40%). LRCP+BFSC group demonstrated defect closure and higher amounts of new bone formation (75 ± 3.5%) but less than AIC+BFSC (82.5 ± 6.45%), suggesting that use of BFSCs within LRCP cage and AIC may enhance bone regeneration in alveolar cleft bone defects; however, the differences were not statistically significant. This clinical trial was registered at clinicaltrial.gov with NCT02859025 identifier.


Developmental expression of p63 in the mouse testis.
p63 is a member of the p53 gene family and have structural similarities with p53. p63 encodes for multiple isotypes either with N-terminal transactivation domain (TAp63) or without it (DeltaNp63). In the mammalian testis, it has been shown that p53 plays important roles in the regulation of germ cell apoptosis and meiosis. However, little is known for the physiological function of p63 in the mammalian spermatogenesis. To investigate the potential roles of p63 in the developing mouse testis, we examined the expression pattern of p63 in the mouse testis from birth to adulthood. In addition to the TAp63 mRNA which was continuously expressed in the developing testis, transcripts encoding DeltaNp63 was detected at specific stages of testicular development by RT-PCR, from postnatal day 1 to day 7 and from 3 weeks to 4 weeks after birth. Western blot analysis of whole testis lysates with anti-p63 antibody revealed an approximately 68 kD band throughout development and a less abundant protein at 60 kD in the earlier period of postnatal development. Immunopositive reactions for p63 were observed as early as 10 days after birth and p63 protein was localized to the nuclei of spermatocytes and round spermatids. These findings strongly suggest that p63 might be involved in the regulation of proliferation and differentiation of spermatogenic cells in the developing mouse testis.


Novel substituted 4-phenyl-[1,3]dioxanes: potent and selective orexin receptor 2 (OX(2)R) antagonists.
Orexins, also termed hypocretins, consist of two neuropeptide agonists (orexin A and B) interacting with two known G-protein coupled receptors (OX(1)R and OX(2)R). In addition to other biological functions, the orexin-2 receptor is thought to be an important modulator of sleep and wakefulness. Herein we describe a series of novel, selective OX(2)R antagonists consisting of substituted 4-phenyl-[1,3]dioxanes. One such antagonist is compound 9, 1-(2,4-dibromo-phenyl)-3-((4S,5S)-2,2-dimethyl-4-phenyl-[1,3]dioxan-5-yl)-urea, which is bound by the OX(2)R with a pK(i) of 8.3, has a pK(b) of 7.9, and is 600-fold selective for the OX(2)R over the OX(1)R.


Anatomical and Topochemical Aspects of Japanese beech (Fagus crenata) Cell Walls After Treatment with the Ionic Liquid, 1-Ethylpyridinium Bromide.
Changes in the ultrastructure and chemical components, and their distribution in Japanese beech (Fagus crenata), during the ionic liquid 1-ethylpyridinium bromide ([EtPy][Br]) treatment were examined at the cellular level by light microscopy, scanning electron microscopy, and confocal Raman microscopy. Each of the tissues, including wood fibers, vessels and parenchyma cells treated with [EtPy][Br] showed specific morphological characteristics. Furthermore, lignin can be preferentially liquefied and eluted in [EtPy][Br] from the cell walls when compared to polysaccharides. However, the delignification was heterogeneous on the cell walls as lignin maintained a relatively high-concentration at the compound middle lamella, cell corners, inner surface of the secondary wall, and pits after [EtPy][Br] treatment.


Selective neural cell adhesion molecule signaling by Src family tyrosine kinases and tyrosine phosphatases.
Nerve growth cone guidance is a highly complex feat, involving coordination of cell adhesion molecules, trophic factor gradients, and extracellular matrix proteins. While navigating through the developing nervous system, the growth cone must integrate diverse environmental signals into a singular response. The repertoire of growth cone responses to these extracellular cues includes axonal growth, fasciculation, and synaptic stabilization, which are achieved through dynamic changes in the cytoskeleton and modulation of gene expression. It has become evident that interactions between cell adhesion molecules can activate intracellular signaling pathways in neurons. Such signaling pathways are just beginning to be defined for the axonal growth promoting molecules L1 and NCAM which are members of the immunoglobulin (Ig) superfamily. Recent findings have revealed that L1 and NCAM induce neurite outgrowth by activating intracellular signaling pathways in the growth cone mediated by two different members of the src family of nonreceptor protein tyrosine kinases (PTKs), pp60(c-src) and p59(fyn5,6). Growth cones display diverse morphologies and variable motility on these different cell adhesion molecules, which are likely to be generated by src kinases. In this review we will address novel features of nonreceptor PTKs of the src family which dictate their distinctive molecular interactions with cell adhesion molecules and signaling components.


Observations of linear aggregation behavior in rotifers (Brachionus calyciflorus).
Linear aggregation is present in some animals, such as the coordinated movement of ants and the migration of caterpillars and spinylobsters, but none has been reported on rotifers. The rotifers were collected and clone cultured in the laboratory at 25 ± 1°C, under natural light (light intensity ~130 lx, L:D = 14:10). The culture medium(pH = 7.3) was formulated as described by Suga et al., and rotifers were fed on the micro algae Scenedesmus obliquus grown in HB-4 medium to the exponential growth stage. When density was high (150 individuals ml-1), the behavior of rotifers was observed using a stereo microscope (Motic ES-18TZLED). In this paper, linear aggregation in Brachionus calyciflorus was found for the first time, and experiments were carried out to verify the correlation between linear aggregation and culture density of B. calyciflorus. With the increase of density, the number of aggregations increase, the number of individuals in the aggregation increased, and the maintenance time of the aggregation was also increased. Therefore, we speculate that the formation of aggregates is related to density and may be a behavioral signal of density increase, which may transmit information between density increase and formation of dormant eggs.


Tolterodine extended release with or without tamsulosin in men with lower urinary tract symptoms including overactive bladder symptoms: effects of prostate size.
Some men with lower urinary tract symptoms (LUTS) including overactive bladder (OAB) symptoms may benefit from antimuscarinic therapy, with or without an alpha-adrenergic antagonist. To evaluate the safety and efficacy of tolterodine extended release (ER), tamsulosin, or tolterodine ER+tamsulosin in men meeting symptom entry criteria for OAB and prostatic enlargement trials, stratified by prostate size. Subjects with an International Prostate Symptom Score (IPSS) >or=12; frequency and urgency, with or without urgency urinary incontinence; postvoid residual volume (PVR) <200 mL; and maximum urinary flow rate (Q(max)) >5 mL/s were randomized to receive placebo, tolterodine ER (4 mg), tamsulosin (0.4 mg), or tolterodine ER+tamsulosin for 12 wk. Data were stratified by median baseline prostate volume (<29 mL vs >or=29 mL). Endpoints included week 12 changes in bladder diary variables, IPSS scores, and safety variables. Among men with larger prostates, tolterodine ER+tamsulosin significantly improved frequency (p=0.001); urgency (p=0.006); and IPSS total (p=0.001), storage (p<0.001), and voiding scores (p<0.013). Tamsulosin significantly improved IPSS voiding scores (p=0.030). Among men with smaller prostates, tolterodine ER significantly improved frequency (p=0.016), UUI episodes (p=0.036), and IPSS storage scores (p=0.005). Tolterodine ER+tamsulosin significantly improved frequency (p=0.001) and IPSS storage scores (p=0.018). Tamsulosin significantly improved nocturnal frequency (p=0.038) and IPSS voiding (p=0.036) and total scores (p=0.044). There were no clinically or statistically significant changes in Q(max) or PVR; incidence of acute urinary retention (AUR) was low in all groups (<or=2%). Men with smaller prostates and moderate-to-severe LUTS including OAB symptoms benefited from tolterodine ER. Therapy with tolterodine ER+tamsulosin was effective regardless of prostate size. Tolterodine ER, with or without tamsulosin, was well tolerated and not associated with increased incidence of AUR.


Ferric Pyrophosphate Forms Soluble Iron Coordination Complexes with Zinc Compounds and Solubilizing Agents in Extruded Rice and Predicts Increased Iron Solubility and Bioavailability in Young Women.
Co-extrusion of ferric pyrophosphate (FePP) with solubilizers, citric acid/trisodium citrate (CA/TSC), or ethylenediaminetetraacetic acid (EDTA) sharply increases iron absorption. Whether this can protect against the inhibition of iron absorption by phytic acid (PA) is unclear. Sodium pyrophosphate (NaPP) may be a new enhancer of iron absorption from FePP. Our objectives were to 1) investigate the ligand coordination of iron, zinc, and solubilizers in extruded rice and test associations with iron solubility and absorption, 2) assess whether co-extrusion of FePP + CA/TSC rice can protect against inhibition of iron absorption by PA; 3) determine the effect of zinc oxide (ZnO) compared with zinc sulfate (ZnSO4), and 4) quantify iron absorption from FePP + NaPP rice. We produced labeled 57FePP rice cofortified with ZnSO4 and EDTA, CA/TSC or NaPP, and FePP + EDTA rice with ZnO. We used electron paramagnetic resonance (EPR) to characterize iron-ligand complexes. We measured in vitro iron solubility and fractional iron absorption (FIA) in young women (n = 21, age: 22 ± 2 y, BMI: 21.3 ± 1.5 kg/m2 geometric mean plasma ferritin, 28.5 μg/L) compared with ferrous sulfate (58FeSO4). FIA was compared by linear mixed-effect model analysis. The addition of zinc and solubilizers created new iron coordination complexes of Fe(III) species with a weak ligand field at a high-spin state that correlated with solubility (r2 = 0.50, P = 0.02) and absorption (r2 = 0.72, P = 0.02). Phytic acid reduced FIA from FePP + CA/TSC rice by 50% (P < 0.001), to the same extent as FeSO4. FIA from FePP + EDTA + ZnO and FePP + EDTA + ZnSO4 rice did not significantly differ. Mean FIAs from FePP + EDTA + ZnSO4, FePP + CA/TSC + ZnSO4, and FePP + NaPP + ZnSO4 rice were 9% to 11% and did not significantly differ from each other or from FeSO4. Rice extrusion of FePP with solubilizers resulted in bioavailable iron coordination complexes. In the case of FePP + CA/TSC, PA exerted similar inhibition of FIA as with FeSO4. FePP + NaPP could be a further viable solubilizing agent for rice fortification. This study was registered at clinicaltrials.gov as NCT03703739.


Energy costs of carbon dioxide concentrating mechanisms in aquatic organisms.
Minimum energy (as photon) costs are predicted for core reactions of photosynthesis, for photorespiratory metabolism in algae lacking CO2 concentrating mechanisms (CCMs) and for various types of CCMs; in algae, with CCMs; allowance was made for leakage of CO2 from the internal pool. These predicted values are just compatible with the minimum measured photon costs of photosynthesis in microalgae and macroalgae lacking or expressing CCMs. More energy-expensive photorespiration, for example for organisms using Rubiscos with lower CO2-O2 selectivity coefficients, would be less readily accommodated within the lowest measured photon costs of photosynthesis by algae lacking CCMs. The same applies to the cases of CCMs with higher energy costs of active transport of protons or inorganic carbon species, or greater allowance for significant leakage from the accumulated intracellular pool of CO2. High energetic efficiency can involve a higher concentration of catalyst to achieve a given rate of reaction, adding to the resource costs of growth. There are no obvious mechanistic interpretations of the occurrence of CCMs algae adapted to low light and low temperatures using the rationales adopted for the occurrence of C4 photosynthesis in terrestrial flowering plants. There is an exception for cyanobacteria with low-selectivity Form IA or IB Rubiscos, and those dinoflagellates with low-selectivity Form II Rubiscos, for which very few natural environments have high enough CO2:O2 ratios to allow photosynthesis in the absence of CCMs.


Pro-Con Debate: Judicious Benzodiazepine Administration for Preoperative Anxiolysis in Older Patients.
In this Pro-Con commentary article, we discuss the risks and benefits of administering preoperative benzodiazepines to older patients to decrease preoperative anxiety. The Pro side first focuses on the critical importance of treating preoperative anxiety and that benzodiazepines are the best tool to achieve that goal. The competing argument presented by the Con side is that myriad options exist to treat preoperative anxiety without simultaneously increasing the risk for devastating complications such as postoperative delirium. Both sides call for more high-quality investigations to determine the most effective strategies for decreasing preoperative anxiety in older adults while improving outcomes and reducing morbidity.


Outcomes of Hypothermia in Addition to Decompressive Hemicraniectomy in Treatment of Malignant Middle Cerebral Artery Stroke: A Randomized Clinical Trial.
Moderate hypothermia in addition to early decompressive hemicraniectomy has been suggested to further reduce mortality and improve functional outcome in patients with malignant middle cerebral artery (MCA) stroke. To investigate whether moderate hypothermia vs standard treatment after early hemicraniectomy reduces mortality at day 14 in patients with malignant MCA stroke. This randomized clinical trial recruited patients from August 2011 through September 2015 at 6 German university hospitals with dedicated neurointensive care units. Of the patients treated with hemicraniectomy and assessed for eligibility, patients were randomly assigned to either standard care or moderate hypothermia. Data analysis was completed from December 2016 to June 2018. Moderate hypothermia (temperature, 33.0 ± 1.0°C) was maintained for at least 72 hours immediately after hemicraniectomy. The primary outcome was mortality rate at day 14 compared with the Fisher exact test and expressed as odds ratio (ORs) with 95% CIs. Rates of patients with serious adverse events were estimated for the period of the first 14 days after hemicraniectomy and 12 months of follow-up. Secondary outcome measures included functional outcome at 12 months. Of the 50 study participants, 24 were assigned to standard care and 26 to moderate hypothermia. Twenty-eight were male (56%); the mean (SD) patient age was 51.3 (6.6) years. Recruitment was suspended for safety concerns: 12 of 26 patients (46%) in the hypothermia group and 7 of 24 patients (29%) receiving standard care had at least 1 serious adverse event within 14 days (OR, 2.05 [95% CI, 0.56-8.00]; P = .26); after 12 months, rates of serious adverse events were 80% (n = 20 of 25) in the hypothermia group and 43% (n = 10 of 23) in the standard care group (hazard ratio, 2.54 [95% CI, 1.29-5.00]; P = .005). The mortality rate at day 14 was 19% (5 of 26 patients) in the hypothermia group and 13% (3 of 24 patients) in the group receiving standard care (OR, 1.65 [95% CI, 0.28-12.01]; P = .70). There was no significant difference regarding functional outcome after 12 months of follow-up. In patients with malignant MCA stroke, moderate hypothermia early after hemicraniectomy did not improve mortality and functional outcome compared with standard care, but may cause serious harm in this specific setting. http://www.drks.de, identifier DRKS00000623.


Serum Vitamin D Levels in Relation to Hypertension and Pre-hypertension in Adults: A Systematic Review and Dose-Response Meta-Analysis of Epidemiologic Studies.
Findings of observational studies that evaluated the association of serum vitamin D status and high blood pressure were contradictory. This meta-analysis of epidemiologic studies assessed the relation of serum vitamin D levels to hypertension (HTN) and pre-hypertension in adults. We conducted a systematic search of all published articles up to March 2021, in four electronic databases (MEDLINE (PubMed), Web of Science (ISI), Embase and Scopus), and Google scholar. Seventy epidemiologic studies (10 prospective cohort, one nested case-control, and 59 cross-sectional investigations) that reported relative risks (RRs), odds ratios (ORs), hazard ratios, or prevalence ratios with 95% CIs for HTN or pre-hypertension in relation to serum vitamin D concentrations in adults were included in the analysis. In prospective studies, a 16% decrease in risk of hypertension was observed in participants with high levels of serum vitamin D compared to low levels (RR: 0.84; 95%CI: 0.73, 0.96; 12 effect sizes). Dose-response analysis in prospective studies revealed that each 25 nmol/L increase in serum vitamin D concentrations resulted in 5% reduced risk of HTN (RR: 0.95; 95% CI: 0.90, 1.00). Also, a significant nonlinear relationship between serum vitamin D levels and HTN was found (Pnonlinearity < 0.001). In cross-sectional investigations, highest vs. lowest level of serum vitamin D was related to reduced odds of HTN (OR: 0.84; 95%CI: 0.79, 0.90; 66 effect sizes) and pre-hypertension (OR: 0.75; 0.95%CI: 0.68, 0.83; 9 effect sizes). Dose-response analysis in these studies showed that each 25 nmol/L increase in serum vitamin D levels was related to a significant 6% reduction in odds of hypertension in all populations (RR: 0.94; 95%CI: 0.90, 0.99) and 3% in studies with representative populations (RR: 0.97; 95%CI: 0.95, 0.99). This meta-analysis of epidemiologic studies disclosed that serum vitamin D concentrations were inversely related to the risk of HTN in adults, in a dose-response manner in both prospective cohort and cross-sectional studies.Systematic Review Registration: http://www.crd.york.ac.uk/Prospero, identifier: CRD42021251513.


[Congenital cutaneous aplasia. Apropos of 3 new cases located in the vertex].
Aplasia cutis congenita is a rare malformation characterized by absence of skin. We report three new cases, localized on the vertex with one appearing as a familial form and requiring an emergent surgical repair with a favorable outcome. After a review of the literature, the authors discuss nosological aspects and etiological problems which are still not resolved. It seems that vascular differentiation of the skin could play an associated role. As regards of treatment, different attitudes are possible and are exposed, with a preference for surgery which is the method of choice for the authors.