Developmental consequences of karyokinesis without cytokinesis during the first mitotic cell cycle of bovine parthenotes.
Bovine parthenogenetic embryos and bovine embryos produced by in vitro fertilization were compared for chromosomal complement and developmental potential. Oocytes (n = 1885) were matured in vitro, fertilized (n = 1151) or activated (n = 734) by exposure to 5 microM ionomycin for 4 min, and then treated with 1.9 mM 6-dimethylaminopurine for 5 h to inhibit protein kinase functions and promote mitosis. Mean cleavage rates at 48 h were 76.3+/-4.7% for fertilization and 60.1+/-4.2% for activation (p < 0.05). A similar percentage of embryos had reached the blastocyst stage on Day 8 post fertilization/postactivation (16.4+/-3.3%) and (15.8+/-1.0%), respectively. Blastocysts (n = 53) produced by in vitro fertilization had higher total cell numbers (116.9+/-5.5) than parthenotes (n = 71, 67.2+/-3.5 cells, p < 0.05). Differential staining indicated a significant reduction in the number of blastomeres allocated to both the inner cell mass and trophectodermal lineages in parthenotes (p < 0.05). All parthenotes (n = 65) were polyploid or mixoploid, with observed karyotypes of 4n (61.53%), 2n/4n (30.76%), 2n/8n (4.61%), and 3n (3.07%). In contrast, only 9 control blastocysts (n = 53) revealed abnormal metaphases (16.9%). At 6 h postactivation (hpa), 70.7% of parthenotes (n = 65) demonstrated a fully formed pronucleus; and at 10 hpa (n = 86), 89% had completed pronuclear formation. Pronuclear DNA replication was observed by 6 hpa and resulted in the formation of a second pronucleus in 76.9% of activated oocytes (n = 104) by 24 hpa. These pronuclear kinetics lead to a high number of embryos with binucleate blastomeres upon cleavage. Thus, alterations in the DNA content (ploidy) of bovine parthenogenetic blastocysts reflect ongoing karyokinesis without cytokinesis during the first mitotic cell cycle after exposure to a protein kinase inhibitor.


Pharmacokinetic Analyses of Liposomal and Non-Liposomal Multivitamin/Mineral Formulations.
Recent research supports previous contentions that encapsulating vitamins and minerals with liposomes help improve overall bioavailability. This study examined whether ingesting a liposomal multivitamin and mineral supplement (MVM) differentially affects the appearance and/or clearance of vitamins and minerals in the blood compared to a non-liposomal MVM supplement. In a double-blind, randomized, and counterbalanced manner, 34 healthy men and women fasted for 12 h. Then, they ingested a non-liposomal (NL) or liposomal (L) MVM supplement and a standardized snack. Venous blood samples were obtained at 0, 2, 4, and 6 h after MVM ingestion and analyzed for a panel of vitamins and minerals. Plasma levels of vitamins and minerals and mean changes from baseline with 95% confidence intervals (CIs) were analyzed using general linear model statistics with repeated measures. The observed values were also entered into pharmacokinetic analysis software and analyzed through univariate analysis of variance with repeated measure contrasts. The results revealed an overall treatment x time interaction effect among the vitamins and minerals evaluated (p = 0.051, ηp2 = 0.054, moderate effect). Differences between treatments were also observed in volume distribution area (vitamin E, iron), median residence time (vitamin E, iron), volume distribution area (iron), volume of distribution steady state (vitamin A, E, iron), clearance rates (vitamin A, E), elimination phase half-life (vitamin E, iron), distribution/absorption phase intercept (vitamin A), and distribution/absorption phase slope and rate (vitamin C, calcium). Vitamin volume distribution was lower with liposomal MVM ingestion than non-liposomal MVM sources, suggesting greater clearance and absorption since similar amounts of vitamins and minerals were ingested. These findings indicate that coating a MVM with liposomes affects individual nutrient pharmacokinetic profiles. Additional research should evaluate how long-term supplementation of liposomal MVM supplements may affect vitamin and mineral status, nutrient function, and/or health outcomes.


Kainic acid lesions disrupt fear-mediated memory processing.
Previous research has shown that hippocampal lesions impair the expression of fear conditioning. This fear conditioning deficit may be due to memory impairment or a reduction in fear in lesioned animals. To address these possibilities, the authors examined unconditioned and conditioned fear in male Sprague-Dawley rats that had received intracerebroventricular (ICV) infusions of kainic acid (KA) 30 days prior to testing. Animals that had received bilateral ICV infusions of KA (1.0 microl of 0.8 mg/ml solution per side) exhibited cell loss that was primarily confined to the CA3 region of the dorsal hippocampus. Kainic acid lesions impaired contextual and cued fear conditioning but did not affect unconditioned fear in a light:dark test of anxiety. Moreover, animals with KA lesions did not habituate to the light:dark apparatus when tested over a 3-day period. These data suggest that decreases in fear conditioning produced by hippocampal lesions reflect a memory deficit and not a lack of fear.


Bone-Specific Enhancement of Antibody Therapy for Breast Cancer Metastasis to Bone.
Despite the rapid evolution of therapeutic antibodies, their clinical efficacy in the treatment of bone tumors is hampered due to the inadequate pharmacokinetics and poor bone tissue accessibility of these large macromolecules. Here, we show that engineering therapeutic antibodies with bone-homing peptide sequences dramatically enhances their concentrations in the bone metastatic niche, resulting in significantly reduced survival and progression of breast cancer bone metastases. To enhance the bone tumor-targeting ability of engineered antibodies, we introduced varying numbers of bone-homing peptides into permissive sites of the anti-HER2 antibody, trastuzumab. Compared to the unmodified antibody, the engineered antibodies have similar pharmacokinetics and in vitro cytotoxic activity, but exhibit improved bone tumor distribution in vivo. Accordingly, in xenograft models of breast cancer metastasis to bone sites, engineered antibodies with enhanced bone specificity exhibit increased inhibition of both initial bone metastases and secondary multiorgan metastases. Furthermore, this engineering strategy is also applied to prepare bone-targeting antibody-drug conjugates with enhanced therapeutic efficacy. These results demonstrate that adding bone-specific targeting to antibody therapy results in robust bone tumor delivery efficacy. This provides a powerful strategy to overcome the poor accessibility of antibodies to the bone tumors and the consequential resistance to the therapy.


Options for the intensification of insulin therapy when basal insulin is not enough in type 2 diabetes mellitus.
In the early treatment of type 2 diabetes mellitus (T2DM), the addition of a basal insulin, such as insulin glargine, to existing oral therapy can help patients attain recommended glycaemic control targets, including haemoglobin A(1c) (HbA(1c)) <7% and fasting blood glucose <5.5 mmol/l (<100 mg/dl). For patients close to but not at target, the management of postprandial glucose excursions with a rapid-acting insulin, such as insulin glulisine, can provide further improvements in glycaemic control. In this review, the options for intensifying insulin therapy with the addition of one or more daily doses of prandial insulin are discussed. In addition, the advantages/disadvantages of choosing a basal-bolus vs. a premixed insulin strategy are discussed. A conceptually simple approach for the treatment of T2DM is for optimization of the basal insulin dose (added to oral antidiabetic drugs) to target fasting glycaemia followed by the addition of a single prandial dose of rapid-acting insulin to target the largest glucose excursion. A second and third dose of prandial insulin can then be added if HbA(1c) remains above target and to manage postprandial glucose excursions at other meals. Prospective studies are underway to further examine this concept and determine the benefit of this approach not only on overall glycaemic control but also on cardiovascular risk.


Mucosal vaccines: novel strategies and applications for the control of pathogens and tumors at mucosal sites.
The mucosal immune system displays several adaptations reflecting the exposure to the external environment. The efficient induction of mucosal immune responses also requires specific approaches, such as the use of appropriate administration routes and specific adjuvants and/or delivery systems. In contrast to vaccines delivered via parenteral routes, experimental, and clinical evidences demonstrated that mucosal vaccines can efficiently induce local immune responses to pathogens or tumors located at mucosal sites as well as systemic response. At least in part, such features can be explained by the compartmentalization of mucosal B and T cell populations that play important roles in the modulation of local immune responses. In the present review, we discuss molecular and cellular features of the mucosal immune system as well as novel immunization approaches that may lead to the development of innovative and efficient vaccines targeting pathogens and tumors at different mucosal sites.


Serum CA125, CA199 and CEA Combined Detection for Epithelial Ovarian Cancer Diagnosis: A Meta-analysis.
To evaluate the diagnostic value of combination detection of serum cancer antigen 125 (CA125), carbohydrate antigen 19-9 (CA199) and carci noembryonic antigen(CEA) in patients with epithelial ovarian cancer by pooling the open published studies according to meta-analysis method. Diagnostic studies related to combination detection of serum CA125, CA199 and CEA in patients with epithelial ovarian cancer were electronic searched in the databases of PubMed, Cochrane, Google scholar, EMBASE, ISI Web of Knowledge and CNKI by two independent reviewers. The combined diagnostic sensitivity, specificity, positive likely hood ratio (+LR), negative likely hood ratio (-LR), diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC) were pooled by Med DiSc1.4 software. Twelve prospective diagnostic publications were finally fulfilled the inclusion criteria and were included in this meta-analysis. The pooled diagnostic sensitivity specificity, positive likely hood ratio, negative likely hood ratio, diagnostic odds ratio, and AUC were 0.90 (95%CI: 0.80 to 0.92), 0.83 (95%CI: 0.80 to 0.86), 5.35(95%CI:3.90 to 7.33), 0.13 (95%CI: 0.10 to 0.16), 48.53 (95%CI: 29.91 to 78.72) and 0.92 (95%C: 0.89 to 0.94) respectively by fixed or random effect model. No publication bias was found according to the funnel plot and line regression test (t=-1.34, P=0.21). Combination detection serum CA125, CA199 and CEA was a promising biomarker forepithelial ovarian cancer diagnosis with relative high sensitivity and specificity.


[Psychological findings in a group of patients with perioral dermatitis].
Female patients suffering from perioral dermatitis were given the Raven Test, two personality inventories (MMPI and FPI) and the Rorschach Test. The results of these four tests show statistically significant differences from controls, indicating emotional immaturity combined with high intelligence level, inability to achieve satisfactory interpersonal relationships contrasting with an overemphasis upon social conformity, and a tendency to 'hysteriform' reactions.


Divergence of desiccation-related traits in two Drosophila species of the takahashii subgroup from the western Himalayas.
Drosophila nepalensis is more abundant under colder and drier montane habitats in the western Himalayas compared with Drosophila takahashii, but the mechanistic basis of such a climatic adaptation is largely unknown. We tested the hypothesis that divergence in the physiological basis of desiccation-related traits is consistent with species-specific adaptations to climatic conditions. Drosophila nepalensis showed approximately twofold higher desiccation resistance, hemolymph content as well as carbohydrate content than D. takahashii despite a modest difference in rate of water loss (0.3% h(-1)). Water loss before succumbing to death (dehydration tolerance) was much higher in D. nepalensis (82.32%) than in D. takahashii (∼50%). A greater loss of hemolymph water under desiccation stress until death is associated with higher desiccation resistance in D. nepalensis. In both species, carbohydrates were utilized under desiccation stress, but a higher level of stored carbohydrates was evident in D. nepalensis. Further, we found increased desiccation resistance in D. nepalensis through acclimation whereas D. takahashii lacked such a response. Thus, species-specific divergence in water-balance-related traits in these species is consistent with their adaptations to wet and dry habitats.


Delayed coronary perforation four days after percutaneous coronary intervention with subsequent cardiac tamponade: A case report.
Coronary artery perforation (CAP) is a rare but lethal complication of percutaneous coronary interventions (PCIs), and its incidence has been increasing with advances in PCI techniques. Delayed CAP presents a highly challenging complication, as it occurs 30 min-9 days after intervention, making subsequent diagnosis and treatment difficult. We present the case of a 63-year-old male patient who underwent PCI for an obtuse marginalis II because of posterior wall myocardial infarction. Following 4 days of uneventful postoperative stay, the patient developed angina pectoris and hypotension 4 h after reinitiation of anticoagulant therapy with edoxaban. Angiography revealed distal vessel perforation from a side branch of the obtuse marginalis II. The vessel was occluded using autologous fat embolization via a microcatheter, resulting in complete sealing of the perforation. After discharge, 4 weeks after the infarction, the patient started rehabilitation therapy. Distal vessel perforations are typically caused by wire damage. In our case, we also suspected distal wire perforation, which was initially not recognized possibly due to distal occlusion through the thrombotic material. The temporal correlation between the re-initiation of anticoagulant therapy and the occurrence of cardiac tamponade suggests that the thrombotic material was resolved due to the former. The management of delayed CAP does not differ from that of CAP; thus, this rare complication should be considered even days after PCI as it could prove lethal if not recognized early.


Concurrent generation of nitric oxide and superoxide damages surfactant protein A.
The conditions under which nitric oxide (.NO) may modulate or promote lung injury have not been identified. We hypothesized that .NO-induced injury results from peroxynitrite, formed by the reaction of .NO with superoxide. The simultaneous generation of .NO and superoxide by 3-morpholinosydnonimine (SIN-1, 0.1-2 mM) resulted in oxidation of dihydrorhodamine, a marker of peroxynitrite production, and a dose-dependent decrease in the ability of SP-A to enhance lipid aggregation. Western blot analysis of SIN-1 exposed SP-A samples, overlaid with a polyclonal antibody against nitrotyrosine, were consistent with nitration of SP-A tyrosine residues. Superoxide dismutase (100 U/ml), L-cysteine (5 mM), xanthine oxidase (10 mU/ml) and xanthine (500 microM), or urate (100 microM) prevented the SIN-1-induced dihydrorhodamine oxidation and injury to SP-A. .NO alone, generated by S-nitroso-N-acetylpenicillamine plus 100 microM L-cysteine, or superoxide and hydrogen peroxide, generated by pterin and xanthine oxidase in the absence of iron, did not damage SP-A or oxidize dihydrorhodamine. We concluded that peroxynitrite, but not .NO or superoxide and hydrogen peroxide, in concentrations likely to be encountered in vivo, caused nitrotyrosine formation and decreased the ability of SP-A to aggregate lipids.


Ion channels regulate energy homeostasis and the progression of metabolic disorders: Novel mechanisms and pharmacology of their modulators.
The progression of metabolic diseases, featured by dysregulated metabolic signaling pathways, is orchestrated by numerous signaling networks. Among the regulators, ion channels transport ions across the membranes and trigger downstream signaling transduction. They critically regulate energy homeostasis and pathogenesis of metabolic diseases and are potential therapeutic targets for treating metabolic disorders. Ion channel blockers have been used to treat diabetes for decades by stimulating insulin secretion, yet with hypoglycemia and other adverse effects. It calls for deeper understanding of the largely elusive regulatory mechanisms, which facilitates the identification of new therapeutic targets and safe drugs against ion channels. In the article, we critically assess the two principal regulatory mechanisms, protein-channel interaction and post-translational modification on the activities of ion channels to modulate energy homeostasis and metabolic disorders through multiple novel mechanisms. Moreover, we discuss the multidisciplinary methods that provide the tools for elucidation of the regulatory mechanisms mediating metabolic disorders by ion channels. In terms of translational perspective, the mechanistic analysis of recently validated ion channels that regulate insulin resistance, body weight control, and adverse effects of current ion channel antagonists are discussed in details. Their small molecule modulators serve as promising new drug candidates to combat metabolic disorders.


General practice and professional coordination.
In a satellite city in South Australia, 17 miles from Adelaide, a controlled experiment in which a social worker from a local community agency has been placed in a four-man practice is demonstrating one way in which new forms of professional coordination can evolve out of already existing services. Through daily face-to-face contact, doctors, and social worker, as well as other surgery staff members, are learning ways of cooperating in unravelling the many mixed medical and psychosocial problems that present in a general practice setting. There are indications that community response to the innovation is positive because the doctors develop an assurance in making referrals, and people see the service as an extension of a known service in an already familiar setting.


[Studies on photoluminescence spectra of polyfluorene under modulation of electric field].
The photoluminescence of polyfluorene thin film modulated by an electric field are studied. The results show that the photoluminescence from polyfluorene film can obviously quenched by the extra electric field, which is attributed to the electric field-induced dissociation of photogeneration excitons. The dependence of the exciton dissociation rate constant on the intensity of electric filed is fitted. The average hopping distance of element charge is 0.68 nm in PFO. This volume is comparable with the reported results in Alq3 and polymers. The spectral dependence of the factor of EFIQP is given. The dissociation of hot-exciton is deduced, which influences on the spectral dependence of the EFIQP factor slightly.


Are silymarin and N-acetylcysteine able to prevent liver damage mediated by multiple factors? Findings against ethanol plus LPS-induced liver injury in mice.
This study investigated the effect of N-acetylcysteine (NAC) and silymarin (SIL) in the liver of mice exposed to ethanol and lipopolysaccharides (LPS). Mice were divided into four groups (n = 6): naive, vehicle, NAC (200 mg/kg), and SIL (200 mg/kg). Treatments were given orally (po) once daily for 10 days. Liver injury was induced by administration of ethanol (30%, po) for 10 days, once daily, followed by a single administration of LPS (2 mg/kg, ip) 24 h before euthanasia. After the treatment period, animals were euthanized, and liver and blood samples were collected. NAC, but not SIL, prevented the increase in oxalacetic glutamic transaminase (OGT) and pyruvic glutamic transaminase (PGT) serum levels. NAC and SIL did not restore levels of reduced glutathione or hepatic malonaldehyde. The treatments with NAC or SIL showed no difference in the activity of glutathione S-transferase, superoxide dismutase, and catalase compared to vehicle group. Myeloperoxidase and N-acetylglucosaminidase activities are increased, as well as the IL-6 and IL-10 levels in the liver. The treatment with NAC, but not SIL, reduced the N-acetylglucosamines activity and the IL-6 and IL-10 amount in the liver. Histological findings revealed microsteatosis in the vehicle group, which was not prevented by SIL but was partially reduced in animals receiving NAC. Unlike other liver injury models, NAC (200 mg/kg) or SIL (200 mg/kg) did not positively affect antioxidant patterns in liver tissue of animals exposed to ethanol plus LPS, but NAC treatment displays anti-inflammatory properties in this model.


Feasibility of Online Neuromodulation Using Transcranial Alternating Current Stimulation in Schizophrenia.
Abnormalities in resting and event-related brain oscillations are known to be associated with cognitive deficits in schizophrenia. Transcranial alternating current stimulation (tACS) modulates these rhythms across the neuronal circuits and could have a potential therapeutic role in psychiatric disorders. In this report, we describe, for the first time, application of online tACS in a schizophrenia patient with working memory deficits. This case report supports the feasibility and potential utility of online tACS in schizophrenia, which needs further systematic research.


Detecting infection hotspots: Modeling the surveillance challenge for elimination of lymphatic filariasis.
During the past 20 years, enormous efforts have been expended globally to eliminate lymphatic filariasis (LF) through mass drug administration (MDA). However, small endemic foci (microfoci) of LF may threaten the presumed inevitable decline of infections after MDA cessation. We conducted microsimulation modeling to assess the ability of different types of surveillance to identify microfoci in these settings. Five or ten microfoci of radius 1, 2, or 3 km with infection marker prevalence (intensity) of 3, 6, or 10 times background prevalence were placed in spatial simulations, run in R Version 3.2. Diagnostic tests included microfilaremia, immunochromatographic test (ICT), and Wb123 ELISA. Population size was fixed at 360,000 in a 60 x 60 km area; demographics were based on literature for Sub-Saharan African populations. Background ICT prevalence in 6-7 year olds was anchored at 1.0%, and the prevalence in the remaining population was adjusted by age. Adults≥18 years, women aged 15-40 years (WCBA), children aged 6-7 years, or children≤5 years were sampled. Cluster (CS), simple random sampling (SRS), and TAS-like sampling were simulated, with follow-up testing of the nearest 20, 100, or 500 persons around each infection-marker-positive person. A threshold number of positive persons in follow-up testing indicated a suspected microfocus. Suspected microfoci identified during surveillance and actual microfoci in the simulation were compared to obtain a predictive value positive (PVP). Each parameter set was referred to as a protocol. Protocols were scored by efficiency, defined as the most microfoci identified, the fewest persons requiring primary and follow-up testing, and the highest PVP. Negative binomial regression was used to estimate aggregate effects of different variables on efficiency metrics. All variables were significantly associated with efficiency metrics. Additional follow-up tests beyond 20 did not greatly increase the number of microfoci detected, but significantly negatively impacted efficiency. Of 3,402 protocols evaluated, 384 (11.3%) identified all five microfoci (PVP 3.4-100.0%) and required testing 0.73-35.6% of the population. All used SRS and 378 (98.4%) only identified all five microfoci if they were 2-3 km diameter or high-intensity (6x or 10x); 374 (97.4%) required ICT or Wb123 testing to identify all five microfoci, and 281 (73.0%) required sampling adults or WCBA. The most efficient CS protocols identified two (40%) microfoci. After limiting to protocols with 1-km radius microfoci of 3x intensity (n = 378), eight identified all five microfoci; all used SRS and ICT and required testing 31.2-33.3% of the population. The most efficient CS and TAS-like protocols as well as those using microfilaremia testing identified only one (20%) microfocus when they were limited to 1-km radius and 3x intensity. In this model, SRS, ICT, and sampling of adults maximized microfocus detection efficiency. Follow-up sampling of more persons did not necessarily increase protocol efficiency. Current approaches towards surveillance, including TAS, may not detect small, low-intensity LF microfoci that could remain after cessation of MDA. The model provides many surveillance protocols that can be selected for optimal outcomes.


Brain and spinal cord revascularization by omental transposition.
It has been learned over the years that placement of the pedicled omentum onto the brain and the spinal cord results in the rapid development of blood vessels that penetrate directly, vertically and deeply into the underlying CNS structure. Rapid clinical changes in some patients following omental transposition to the CNS raised the question as to whether the changes might be due not only to increased vascular perfusion, but to neurochemicals within omental tissue. Subsequent studies have shown that the omentum incorporates in its tissue neurotransmitters, nerve growth substances, gangliosides and angiogenic factors of high activity. These neurochemical and angiogenic substances are undoubtedly involved in some manner in the ability of axons in a transected spinal cord to grow at 1 mm/day and apparently make appropriate connections with distal spinal cord target tissue.


Single-mode laser by parity-time symmetry breaking.
Effective manipulation of cavity resonant modes is crucial for emission control in laser physics and applications. Using the concept of parity-time symmetry to exploit the interplay between gain and loss (i.e., light amplification and absorption), we demonstrate a parity-time symmetry-breaking laser with resonant modes that can be controlled at will. In contrast to conventional ring cavity lasers with multiple competing modes, our parity-time microring laser exhibits intrinsic single-mode lasing regardless of the gain spectral bandwidth. Thresholdless parity-time symmetry breaking due to the rotationally symmetric structure leads to stable single-mode operation with the selective whispering-gallery mode order. Exploration of parity-time symmetry in laser physics may open a door to next-generation optoelectronic devices for optical communications and computing.


The upregulation of plasticity-related proteins following TBI is disrupted with acute voluntary exercise.
Following traumatic brain injury (TBI), the brain undergoes a period of metabolic and neurochemical alterations that may compromise the reactivity of neuroplasticity-related molecular systems to physiological stimulation. In order to address the molecular mechanisms underlying plasticity following TBI and the effects of physical stimulation in the acute phase of TBI, levels of intracellular signaling molecules were assessed following voluntary exercise. Lateral fluid percussion injury (FPI) and sham-operated (Sham) rats were housed with or without access to a running wheel (RW) from postsurgery day 0 to 6. Parietal and occipital cortical tissues were analyzed for brain-derived neurotrophic factor (BDNF) using an enzyme-linked immunoabsorbant assay (ELISA). In addition, synapsin I, phospho-synapsin I, cyclic-AMP response-element-binding protein (CREB), phospho-CREB, calcium-calmodulin-dependent protein kinase II (CAMKII), mitogen-activated protein (MAP) kinase I and II (MAPKI and MAPKII), and protein kinase C (PKC) were analyzed by western blot. Results from this study indicated that FPI alone lead to significant increases in synapsin I, CAMKII, and phosphorylated (P) MAPKI (p44) and MAPKII (p42). Exercise in the sham operates led to significant cortical increases of CREB and synapsin I. However, in the FPI rats, the response to exercise was opposite to that seen in the shams in that exercise resulted in significant decreases of CREB, synapsin I, PKC, CAMKII, MAPKI, and MAPKII. Indeed, all the observed proteins in the acutely exercised FPI rats tended to be lower compared to the FPI sedentary (Sed) rats. These results indicate that intracellular signaling proteins are increased during the first week following FPI and that premature voluntary exercise may compromise plasticity.


Coexistence of incontinentia pigmenti and neonatal herpes simplex virus infection.
We present a female infant with classic clinical and histologic features of stage I incontinentia pigmenti with coexistent neonatal herpes simplex virus infection. The diagnosis of a heritable cutaneous condition does not exclude the possibility of a coexistent infection and, given the similar clinical presentation of neonatal vesicular eruptions, accurate diagnoses may require skin biopsy and culture.


Usage of reaction kinetics data stored in databases - a modeler's point of view.
Computational approaches to biochemistry like modeling and simulation are dependent on the availability of kinetic information. This information can either be directly derived from experimental data generated by collaborators or has to be digged up from literature, often both. More recently, data stored in databases has started to be a valuable addition as a source of enzyme kinetic data. In order to faciliate modeling and simulation, various tools have been developed in recent years. However, automatizing steps in setting up, analyzing or simulating models requires the data to be in defined formats. Crucial points are addressed below.


Skin rash as early presentation of Guillain-Barré syndrome.
We report an unusual case of Guillain-Barre syndrome in a 36-year old gentleman, diagnosed based on clinical presentation, CSF analysis and nerve study tests findings, who presented to our department for elective cystoscopy and discovered at the day of surgery to have macular skin rash over the trunk and upper limbs, surgery was postponed. Then and after 12 hours he started to develop the classical manifestations of Guillain-Barre syndrome. Asymptomatic skin rash should carefully be investigated as it could be an early presentation of a serious condition.


The physiological role of copper and the problems of copper nutritional deficiency.
The paper deals with recent achievements concerning the physiological role of copper in the human organism. The problem of copper supplementation of the human diet is discussed. An outlook is given on the contemporary theories referring to the role of copper in nutrition. Special attention has been paid to the copper-containing enzymes and copper-dependent enzymes as well as to the problem of nutritional copper deficiencies. This paper shows the necessity of copper for: --"cleaning" of the organism from the excesses of free radicals, biogenic amines and cholesterol --the proper synthesis of hemoglobin, elastin, collagen and probably thyroid hormones --providing the energy formed in the respiratory chain and needed for biochemical syntheses and proper physical activity.


Fructose-enriched diet induces inflammation and reduces antioxidative defense in visceral adipose tissue of young female rats.
The consumption of refined, fructose-enriched food continuously increases and has been linked to development of obesity, especially in young population. Low-grade inflammation and increased oxidative stress have been implicated in the pathogenesis of obesity-related disorders including type 2 diabetes. In this study, we examined alterations in inflammation and antioxidative defense system in the visceral adipose tissue (VAT) of fructose-fed young female rats, and related them to changes in adiposity and insulin sensitivity. We examined the effects of 9-week fructose-enriched diet applied immediately after weaning on nuclear factor κB (NF-κB) intracellular distribution, and on the expression of pro-inflammatory cytokines (IL-1β and TNFα) and key antioxidative enzymes in the VAT of female rats. Insulin signaling in the VAT was evaluated at the level of insulin receptor substrate-1 (IRS-1) protein and its inhibitory phosphorylation on Ser307. Fructose-fed rats had increased VAT mass along with increased NF-κB nuclear accumulation and elevated IL-1β, but not TNFα expression. The protein levels of antioxidative defense enzymes, mitochondrial manganese superoxide dismutase 2, and glutathione peroxidase, were reduced, while the protein content of IRS-1 and its inhibitory phosphorylation were not altered by fructose diet. The results suggest that fructose overconsumption-related alterations in pro-inflammatory markers and antioxidative capacity in the VAT of young female rats can be implicated in the development of adiposity, but do not affect inhibitory phosphorylation of IRS-1.


Induction of differentiation and covalent binding to proteins by the synthetic retinoids Ch55 and Am80.
all-trans-Retinoic acid (RA) is a potent inducer in vitro of the differentiation of the human acute myeloid leukemia cell line HL60. A mechanism for RA-induced differentiation of HL60 cells may involve retinoylation (RA acylation) which is a post-translational modification of proteins occurring in many eukaryotic cell lines. Here, we found that differentiation by the synthetic retinoid (E)4-[3-(3,5-di-tert-butylphenyl)-3-oxo-1-propenyl]-benzoic acid (Ch55) was dose-dependent in serum-free medium. The synthetic retinoid 4(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenylcarbamoyl) benzoic acid (Am80) did not induce differentiation. Ch55 bound covalently to proteins of HL60 cells. In contrast, covalent binding of Am80 to HL60 proteins was much lower. Two-dimensional gel electrophoresis patterns of proteins labeled covalently by RA and Ch55 were different with few proteins labeled by both retinoids. The level of retinoylation was increased by Am80 and combinations of RA with either Ch55 or Am80 synergistically induced differentiation of HL60 cells. These results suggest that covalent modification of proteins by a retinoid may play a role in inducing differentiation of HL60 cells. In addition, the synergy seen with combinations of RA and either Ch55 or Am80 suggests that some synthetic retinoids may be active because they displace RA from intracellular sites or because they inhibit RA catabolism.


Membrane acoustic metamaterial absorbers with magnetic negative stiffness.
A membrane absorber usually requires a large back cavity to achieve low-frequency sound absorption. This paper describes the design of a membrane acoustic metamaterial absorber in which magnetic negative stiffness is employed to reduce the size of the back cavity. As a baseline for the present research, analysis of a typical membrane sound absorber based on an equivalent circuit model is presented first. Then, a theoretical model is established by introducing negative stiffness into a standard absorber. It is demonstrated that a small cavity with negative stiffness can achieve the acoustic impedance of a large cavity and that the absorption peak is shifted to lower frequencies. Experimental results from an impedance tube test are also presented to validate this idea and show that negative stiffness can be employed to design compact low-frequency membrane absorbers.


Permeability of dog lung endothelium to sodium, diols, amides, and water.
Bolus injection of T-1824-albumin, test indicator, and tritiated water into a jugular vein of the anesthetized dog and sequential sampling of blood from a carotid artery yielded multiple-indicator outflow patterns for the lung. Permeability-surface products of the test indicator for the lung endothelial barrier were obtained by comparison of test indicator with T-1824-albumin on the upslope of the test-indicator curve and correction for backdiffusion. The derived endothelial permeability coefficients, based on surface area/wet lung weight-500 cm2/g (mean +/- 2 SE, 10(-5) cm s(-1)), were: sodium ion, 2.9 +/- 0.8; ethylene glycol, 7.3 +/- 1.5; 1, 3-propranediol, 7.9 +/- 3.2; 1, 2-propanediol, 10 +/- 4; 1, 4-butanediol, 14 +/- 8; 1, 5-pentanediol, 21 +/- 6; 1, 6-hexanediol, 41 +/- 11; formamide, 16 +/- 9; acetamide, 13 +/- 4; propionamide, 31 +/- 12; butyramide, 42 +/- 24; valeramide, 79 +/- 12; tritiated water, 150 +/- 50. The backdiffusion correction varies from 8% for sodium to 75% for valeramide. A parallel-pathway model of blood-tissue passive exchange of small nonelectrolyte solutes is compatible with these results, with a lipid pathway through endothelial cells and an aqueous pathway possibly through interendothelial clefts.


Bone marrow transplantation and approaches to avoid graft-versus-host disease (GVHD).
Haematopoietic stem cell transplantation (HSCT) offers promise for the treatment of haematological and immune disorders, solid tumours, and as a tolerance inducing regimen for organ transplantation. Allogeneic HSCTs engraftment requires immunosuppression and the anti-tumour effects are dependent upon the immune effector cells that are contained within or generated from the donor graft. However, significant toxicities currently limit its efficacy. These problems include: (i) graft-versus-host disease (GVHD) in which donor T cells attack the recipient resulting in multi-organ attack and morbidity, (ii) a profound period of immune deficiency following HSCT, and (iii) donor graft rejection. Currently available methods to prevent or treat GVHD with systemic immunosuppression can lead to impaired immune recovery, increased opportunistic infections, and higher relapse rates. This review will provide an overview of GVHD pathophysiology and discuss the roles of various cells, pathways, and factors in the GVHD generation process and in the preservation of graft-versus-tumour effects. Variables that need to be taken into consideration in attempting to extrapolate preclinical results to the clinical paradigm will be highlighted.


Structural studies of Vgamma2Vdelta2 T cell phosphoantigens.
Human gammadelta T cells containing the Vgamma2Vdelta2 (Vgamma9Vdelta2) T cell receptor are stimulated by a broad variety of small, phosphorus-containing antigenic molecules called phosphoantigens. The structures of several species present in both Mycobacteria (TUBags1-4) and in Escherichia coli have been reported to contain a formyl-alkyl diphosphate core. Here we report the synthesis of the lead member of the series, 3-formyl-1-butyl diphosphate. This compound has low activity for gammadelta T cell stimulation, unlike its highly active isomer (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate, necessitating a revision of the structure of TUBag1. Likewise, the structure of the species identified as the pentyl analog (TUBag 2) is revised to 6-phosphogluconate. These results indicate that neither TUBag1 nor the m/e 275 species proposed for TUBag2 are 3-formyl-1-alkyl diphosphates, leading to the conclusion that none of the natural phosphoantigens (TUBags1-4) possess the structures reported previously.


Executive dysfunctions across adulthood: measurement properties and correlates of the DEX self-report questionnaire.
Difficulties in executive processes can disturb daily life functioning. Using data obtained from two independent community-dwelling samples (n(1) = 468, n(2) = 669, 18-97 years), we examined the factor structure of the Dysexecutive Functioning Questionnaire (DEX) and explored the frequencies and potential correlates of self-reported executive difficulties. Our results revealed that executive problems are parsimoniously described with one underlying factor. Everyday executive dysfunctions were moderately frequent throughout adulthood. Reports of executive problems were associated with individual difference characteristics including age, subjective health, personality, affect, and cognition. We also found that, although executive functions are known to decline with advancing adult age, younger age groups reported more problems than older groups, an effect that was partially mediated by a negative affect factor. We discuss implications for the validity of the instrument as well as directions for future research on executive functioning difficulties in everyday life.


Ultrasonography and CT examination of ovarian follicular development in 'Testudo graeca' during 1 year in captivity.
The Greek or Mediterranean tortoise (Testudo graeca), commonly known as the spur-thighed tortoise, is a species of tortoise in the family Testudinidae that is found in North Africa, Western Asia and Europe. Several species of this genus are under threat in the wild, mainly from habitat destruction therefore, accurate information about the sexual cycle and the exact time of follicular development can be effective in successful reproduction planning and preventing species extinction. The experimental part of this study is focused on the evaluation of the reproductive apparatus of tortoises and development of follicles in ovaries during 1 year by ultrasonography and computed tomography. Ultrasonography and CT scanning was carried out on 10 female 'T. Graeca' tortoises which were maintained at Tehran Eram Zoo from November 2021 to November 2022 (1 year). Ultrasonography and CT exams were performed on all animals. In the first study, on 28 November 2021, the ovarian cycle was characterized by the presence of previtellogenic follicles and atretic follicles. The numbers of follicles were best demonstrated on CT examination. Ultrasonography and CT scan in the second study showed no change in type of follicles from previous study. In the third study, atretic follicles were more than previtellogenic follicles, whereas in the fourth one, the numbers of previtellogenic follicles were more than atretic follicles. In following, at 6 and 29 June 2022, the absence of atretic follicles and just presence of previtellogenic follicles were observed. On 20 July 2022, the presence of a few number of atretic follicles and more previtellogenic follicles were noticed. On 30 July 2022, the absence of atretic follicles and presence of previtellogenic follicles and, for the first time, preovulatory follicles were obvious. In four following studies the absence of atretic follicles and the presence of previtellogenic follicles were diagnosed. In the last study, the absence of atretic follicles and the presence of preovulatory and previtellogenic follicles were observed. In current study, the reproductive cycle of female T. Graeca is evaluated during 1 year in captivity with ultrasonography and CT scan. It can be concluded that in captivity, the reproductive cycle does not result in the formation of eggs or calcareous shells and atretic follicles in the study year continued as before; so this should be highly considered in captivity breeding programmes. This study also revealed that among imaging modalities, CT scan is the best modality for detecting the shape, size, type and numbers of the follicles for further evaluation of location and shape of the follicles.


An Arabidopsis gene network based on the graphical Gaussian model.
We describe a gene network for the Arabidopsis thaliana transcriptome based on a modified graphical Gaussian model (GGM). Through partial correlation (pcor), GGM infers coregulation patterns between gene pairs conditional on the behavior of other genes. Regularized GGM calculated pcor between gene pairs among approximately 2000 input genes at a time. Regularized GGM coupled with iterative random samplings of genes was expanded into a network that covered the Arabidopsis genome (22,266 genes). This resulted in a network of 18,625 interactions (edges) among 6760 genes (nodes) with high confidence and connections representing approximately 0.01% of all possible edges. When queried for selected genes, locally coherent subnetworks mainly related to metabolic functions, and stress responses emerged. Examples of networks for biochemical pathways, cell wall metabolism, and cold responses are presented. GGM displayed known coregulation pathways as subnetworks and added novel components to known edges. Finally, the network reconciled individual subnetworks in a topology joined at the whole-genome level and provided a general framework that can instruct future studies on plant metabolism and stress responses. The network model is included.


Production of an active recombinant thrombomodulin derivative in transgenic tobacco plants and suspension cells.
Thrombomodulin is a membrane-bound protein that plays an active role in the blood coagulation system by binding thrombin and initiating the protein C anticoagulant pathway. Solulin is a recombinant soluble derivative of human thrombomodulin. It is used for the treatment of thrombotic disorders. To evaluate the production of this pharmaceutical protein in plants, expression vectors were generated using four different N-terminal signal peptides. Immunoblot analysis of transiently transformed tobacco leaves showed that intact Solulin could be detected using three of these signal peptides. Furthermore transgenic tobacco plants and BY2 cells producing Solulin were generated. Immunoblot experiments showed that Solulin accumulated to maximum levels of 115 and 27 microg g(-1) plant material in tobacco plants and BY2 cells, respectively. Activity tests performed on the culture supernatant of transformed BY2 cells showed that the secreted Solulin was functional. In contrast, thrombomodulin activity was not detected in total soluble protein extracts from BY2 cells, probably due to inhibitory effects of substances in the cell extract. N-terminal sequencing was carried out on partially purified Solulin from the BY2 culture supernatant. The sequence was identical to that of Solulin produced in Chinese hamster ovary cells, confirming correct processing of the N-terminal signal peptide. We have demonstrated that plants and plant cell cultures can be used as alternative systems for the production of an active recombinant thrombomodulin derivative.


Empirical evaluation of language modeling to ascertain cancer outcomes from clinical text reports.
Longitudinal data on key cancer outcomes for clinical research, such as response to treatment and disease progression, are not captured in standard cancer registry reporting. Manual extraction of such outcomes from unstructured electronic health records is a slow, resource-intensive process. Natural language processing (NLP) methods can accelerate outcome annotation, but they require substantial labeled data. Transfer learning based on language modeling, particularly using the Transformer architecture, has achieved improvements in NLP performance. However, there has been no systematic evaluation of NLP model training strategies on the extraction of cancer outcomes from unstructured text. We evaluated the performance of nine NLP models at the two tasks of identifying cancer response and cancer progression within imaging reports at a single academic center among patients with non-small cell lung cancer. We trained the classification models under different conditions, including training sample size, classification architecture, and language model pre-training. The training involved a labeled dataset of 14,218 imaging reports for 1112 patients with lung cancer. A subset of models was based on a pre-trained language model, DFCI-ImagingBERT, created by further pre-training a BERT-based model using an unlabeled dataset of 662,579 reports from 27,483 patients with cancer from our center. A classifier based on our DFCI-ImagingBERT, trained on more than 200 patients, achieved the best results in most experiments; however, these results were marginally better than simpler "bag of words" or convolutional neural network models. When developing AI models to extract outcomes from imaging reports for clinical cancer research, if computational resources are plentiful but labeled training data are limited, large language models can be used for zero- or few-shot learning to achieve reasonable performance. When computational resources are more limited but labeled training data are readily available, even simple machine learning architectures can achieve good performance for such tasks.


Extension of hydrogen borrowing alkylation reactions for the total synthesis of (-)-γ-lycorane.
The total synthesis of (-)-γ-lycorane (10 steps) and synthesis of (±)-γ-lycorane (8 steps) was completed from cyclohexenone. A new two step hydrogen borrowing alkylation of an aziridinyl alcohol, coupled with a Ph* (Me5C6) deprotection/cyclisation procedure was developed for de novo formation of the fused 6,5 heterocyclic ring. This work is one of the first examples of hydrogen borrowing C-C bond formation being used as a key step in a total synthesis project.


[ENT medical findings in obstructive sleep apnea syndromes].
Correlations between the manifestation of obstructive sleep apnoea syndrome (OSAS) and anatomical or functional changes in the upper respiratory tract remain controversial. The correlation between obstruction of the upper respiratory tract and the degree of sleep apnoea syndrome was investigated in 60 patients with obstructive sleep apnoea (diagnosed by polysomnography) and in 55 healthy controls. After clinical examination, rhinomanometry and determination of the size of the lower jaw and oropharynx, the motility of the pharyngeal walls during Mueller's manoeuvre was evaluated by flexible endoscopy. No significant anatomical or functional differences were observed between OSAS patients and healthy controls. There was no correlation between the degree of OSAS (expressed by the apnoea index) and pharyngeal size. Although no specific statement concerning diagnosis or degree of OSAS can be made on the basis of an otolaryngological examination, OSAS patients should always undergo otolaryngological examination to exclude pharyngeal disease.


Difference in the breakfast habits of overweight/obese and normal weight schoolchildren.
The aim of the present study was to analyse the differences between the breakfast habits of obese/overweight (O) (those with body mass index [BMI] above the 75th percentile) and normal weight schoolchildren (N) (those with BMI equal to or below the 75th percentile). A seven consecutive days "food record" was used to record the intake of foods at breakfast and throughout the rest of the day. O subjects, and in particular female O subjects, omitted breakfast more frequently and took significantly smaller quantities of cereals than did N subjects. The energy supplied by breakfast, measured as a percentage of energy expenditure, was significantly lower in O subjects (17.0 +/- 8.5% in males and 14.6 +/- 6.1% in females) than in N subjects (20.9 +/- 9.4% in males and 17.6 +/- 6.5% in females). With respect to the energy and nutrients supplied by breakfast, O subjects took lower quantities of carbohydrates, thiamin, niacin, pyridoxine, vitamin D and iron than did N subjects. The energy profiles of O subjects breakfasts were more imbalanced than those of N subjects. A significant difference was seen between the amounts of energy supplied by carbohydrates. Without doubt, O subjects have less satisfactory breakfast habits than N subjects. This might be a reflection of whole diet that is less adequate, however, it is possible that an inadequate breakfast contributes to the making of poor food choices over the rest of the day, and, in the long term, to an increased risk of obesity.


Refinement Impairments of Verbal-Performance Intelligent Quotient in Children Exposed to Fluoride Produced by Coal Burning.
To explore the relationship between total intelligence quotient (IQ), verbal intelligence quotient (VIQ), performance intelligence quotient (PIQ), and fluoride exposure in children aged 8-12 years in coal-burning fluorosis area of Dafang County, Guizhou Province, China. The Wechsler Intelligence Scale for Children Revised in China (WISC-CR) was used to test the total IQ, VIQ, and PIQ in 99 children aged 8-12 years (55 in dental fluorosis group and 44 in control group). The differences in the intellectual levels between the two groups were compared, and the correlation between the intellectual level of children exposed to fluoride and the exposure dose of fluoride was analyzed. The VIQ, PIQ, and total IQ in the dental fluorosis group were 85.64 ± 16.53, 94.87 ± 12.73, and 88.51 ± 12.77, respectively, and these were lower than those in the control group (94.34 ± 16.04, 99.23 ± 12.44, and 96.64 ± 11.70, respectively). Significant difference was observed in VIQ and total IQ between the two groups (P = 0.002, P = 0.01), but not in the PIQ (P > 0.05). Each item of VIQ impairment (common sense, similar, arithmetic, vocabulary, and understanding) was significantly lower than those without VIQ impairment in the dental fluorosis group (P < 0.05). There was a significant difference in two items of building blocks and decoding between PIQ impairment and normal group (P < 0.05). Children with fluorosis in coal-burning areas had impaired IQ and obviously had impaired VIQ. Thus, the language learning ability should be strengthened in children exposed to fluorosis.


[Non-insulin therapy in diabetes mellitus].
Changes to nutritional habits, including the reduction of weight, are basic therapy principles for the treatment of diabetes mellitus. With overweight patients a reduction of energy intake is important. Patients with diabetes mellitus should eat plenty of carbohydrates, the intake of fat should be limited to a maximum of 35%. Patients treated with insulin must be made to calculate carbohydrate exchange units. Unless there are contraindications, diabetic patients should be encouraged to engage in physical exercise. Educating the patients is of major importance in the treatment of diabetics; this must be undertaken by trained personnel. All diabetic patients treated with oral antidiabetic drugs or insulin should be encouraged to measure their blood glucose levels themselves, in cases of insulin therapy this is an absolutely necessity. If with the aid of basic therapy measures, which include the control of fasting blood glucose, postprandial blood glucose and HbA1c levels, the aims of the therapy are not reached, this is an indication for the use of oral antidiabetic drugs. The drug should be chosen with the dominant pathophysiological disturbance in mind. In the case of increased fasting blood glucose values (hepatic insulin resistance leading to increased glucose production by the liver), after contraindications have been excluded, the use of metformin is recommended. If there are significantly increased postprandial blood glucose values (due to an early-insulin-secretion deficiency or severe insulin resistance), the use of alpha-glucosidase-inhibitors, metformin, sulphonylureas or glinides is indicated. With obese patients alphaglucosidaseinhibitors and metformin are the drugs of choice, with patients with BMI < 25 kg/m2 these are sulfonylureas or glinides. In cases of severe insulin resistance the use of glitazones in conjunction with metformin or sulphonylureas may be indicated.


Acupuncture methods for diabetic peripheral neuropathy: A protocol for a Bayesian network meta-analysis.
Many clinical trials and systematic reviews have suggested that acupuncture (include moxibustion) could be effective in the treatment of diabetic peripheral neuropathy (DPN). However, clinical practices vary greatly leads to different choices which are mainly based on personal experience. The aim of this Bayesian network meta-analysis is to compare the efficacy of different acupuncture methods for DPN. Randomized controlled trials on acupuncture treatment of DPN published before January of 2021 will be searched in 9 databases including Medline, Web of Science, PubMed, Cochrane Library, Excerpta Medica Database, Sinomed, China National Knowledge Infrastructure, WanFang, and China Science and Technology Journal Database. The methodological assessment performed using the risk of bias assessment tool of Cochrane, and the level of evidence quality for the main results will be evaluated by a recommended grading, evaluation, formulation, and evaluation system approach. Bayesian network meta-analysis will be conducted using STATA V.14.0 and WinBUGS V.1.4.3. The primary outcome involves: clinical efficacy. The secondary outcomes include: motor nerve conduction velocity, sensory nerve conduction velocity, Toronto clinical scoring system, Michigan neuropathy screening instrument, the modified Toronto Clinical Neuropathy Scale, the Utah early neuropathy scale, or the neuropathy disability score, and adverse reactions. To find the most effective acupuncture therapy for the treatment of DPN supported by evidence-based medicine.


Genistein as a neuroprotective antioxidant attenuates redox imbalance induced by beta-amyloid peptides 25-35 in PC12 cells.
Genistein (GEN), a principal component of soybean isoflavones, might possess the neuroprotective role through its antioxidant activity. However, the detailed mechanisms are unknown yet. The purpose of this study was to investigate whether GEN could alleviate oxidative damage induced by beta-amyloid peptides 25-35 (Abeta25-35) in PC12 cells. The PC12 cells were pre-incubated with or without GEN for 2h following incubation with Abeta25-35 for another 24h. MTT was used to assess the cell viability. Hoechst 33342 staining was applied to determine the apoptotic cells. Confocal laser scanning microscopy was implemented to examine the reactive oxygen species (ROS) levels. Mitochondrial membrane potential (MMP) was measured by flow cytometry. Reduced and oxidized glutathione (GSH/GSSG) ratio was analyzed by using assay kits. Western blot analysis was performed to assess the proteins expression of NF-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and gamma-glutamylcysteine synthetase (gamma-GCS). GEN attenuated the cytotoxicity and partially prevented apoptosis induced by Abeta25-35. GEN dramatically attenuated ROS levels induced by Abeta25-35 in PC12 cells. In addition, GEN significantly reversed the reduction of MMP caused by Abeta25-35 to maintain the normal levels of the cells. The GSH/GSSG ratio in GEN pretreated groups significantly increased compared to the groups without GEN pretreatment. GEN reversed Abeta25-35 induced down regulation of the protein expression of gamma-GCS, Nrf2 and HO-1. GEN could alleviate the oxidative stress caused by Abeta25-35 treatment and maintain redox balance in PC12 cells, which might be associated with the regulation of Nrf2/HO-1 signal pathway.


Associations between cognitive abilities and life satisfaction in the oldest-old. Results from the longitudinal population study Good Aging in Skåne.
Studies on the associations between cognitive abilities and life satisfaction (LS) in the oldest-old are few. The aim of this study was to explore whether abilities in six different cognitive domains could predict LS in the oldest-old 3 years later. The study population consisted of 681 individuals aged 78-98 years, drawn from the longitudinal population study "Good Aging in Skåne," which is part of a national survey (The Swedish National Study on Aging and Care). Scores on 13 cognitive tests were related to scores on Neugartens' LS index A (LSI-A) 3 years later. The cognitive tests were added into six different cognitive domains. A multiple regression analysis was constructed for each cognitive domain separately, with scores on the LSI-A as the dependent variable. The model was adjusted stepwise for sex, age, education, functional capacity, and depressive mood. Significant correlations were found between digit cancellation, word recall, verbal fluency (VF) A, VF animals, VF occupations, and mental rotations at baseline, as well as LSI-A at follow-up. The domains of spatial abilities (B = 0.453, P = 0.014) and processing speed (B = 0.118, P = 0.020) remained significantly associated with LSI-A 3 years later after adjustment. The cognitive domains of spatial abilities and processing speed predicted LS 3 years later in the oldest-old. Clinical implications are discussed.


Recruitment of ZipA to the division site by interaction with FtsZ.
ZipA is an essential cell division protein in Escherichia coli that is recruited to the division site early in the division cycle. As it is anchored to the membrane and interacts with FtsZ, it is a candidate for tethering FtsZ filaments to the membrane during the formation of the Z ring. In this study, we have investigated the requirements for ZipA localization to the division site. ZipA requires FtsZ, but not FtsA or FtsI, to be localized, indicating that it is recruited by FtsZ. Consistent with this, apparently normal Z rings are formed in the absence of ZipA. The interaction between FtsZ and ZipA occurs through their carboxy-terminal domains. Although a MalE-ZipA fusion binds to FtsZ filaments, it does not affect the GTPase activity or dynamics of the filaments. These results are consistent with ZipA acting after Z ring formation, possibly to link the membrane to FtsZ filaments during invagination of the septum.


Reassessment of Postural Stimulation Testing as a Simple Tool to Identify a Subgroup of Patients With Unilateral Primary Aldosteronism.
Adrenal vein sampling (AVS) represents the current diagnostic gold standard for differentiation between unilateral and bilateral primary aldosteronism (PA). Postural stimulation testing (PST) has been used to provide additional diagnostic information. This work aimed to evaluate the diagnostic utility of PST in the differential diagnosis of PA. This cohort study was conducted at a single tertiary reference center. We analyzed 106 PST performed between 2008 and 2020. Diagnosis of PA and cause of PA were determined according to the Endocrine Society Clinical Practice Guideline, taking into account results of saline infusion testing, AVS, preoperative imaging, and outcome after medical or surgical treatment. The suggested cutoffs for the diagnosis of unilateral PA were revisited and optimized for high specificity using receiver operating characteristics (ROC) analysis. A total of 106 patients had confirmed PA (unilateral PA: n = 55, bilateral PA: n = 29, AVS unsuccessful/declined by patients: n = 22). Based on decreased aldosterone plasma concentration of 28% or more after 4 hours in the upright position, the PST showed a sensitivity of 36.4% at a specificity of 100% to identify unilateral disease (area under the curve [AUC] = 0.72; 95% CI, 0.62-0.83; P = .001). In patients with valid testing (drop of cortisol of 10% or more after 4 hours, n = 53) the sensitivity of PST rose to 51.4% at a specificity of 100% (AUC = 0.77; 95% CI, 0.65-0.90; P = .001). The high specificity of 100% for the detection of unilateral PA in patients with decreased aldosterone by at least 28% after 4 hours makes PST a simple, noninvasive contribution to subtype differentiation in PA.


White blood cell counting at point-of-care testing: A review.
White blood cells, which are also called leukocytes, are found in the immune system that are involved in protecting the body against infections and foreign invaders. Conventional methods of leukocyte analysis provide valuable and accurate information to medical specialists. Analyzing and diagnosing of a disease requires a combination of multiple biomarkers, in some cases, however, such as personal health care, this will occupy some medical resources and causes unnecessary consumption. Traditional method (such as flow cytometer) for WBC counting is time and labor consuming. Compared to gold standard (flow-based fraction/micropore filtration) or improved filtration methods for WBC counting, this is still a lengthy and time consuming process and can lead to membrane fouling due to the rapid accumulation of biological materials. Therefore, the analysis of WBC counts requires more compact and efficient equipment. The microfluidic technologies, powered by different field (force, thermal, acoustic, optical, magnetic) and other methods for leukocyte counting and analysis, are much cost-efficient and can be used in in-home or in resource-limited areas to achieve Point-of-Care (POC). In this review, we highlight the mainstream devices that have been commercialized and extensively employed for patients for WBC counting, Next, we present some recent development with regards to leucocyte counting (mainly microfluidic technologies) and comment on their relative merits. We aim to focus and discuss the possibility of achieving POC and help researchers to tackle individual challenges accordingly. Finally, we offer some technologies in addition to previous detection devices, such as image recognition technology and cloud computing, which we believe have great potential to further promote real-time detection and improve medical diagnosis.


Biochemical characterization of Ia alloantigens in guinea pigs. I. Synthesis of Ia antigens by subsets enriched for B cells, T cells, or macrophages.
Peritoneal exudate cells from immune guinea pigs consist primarily of T lymphocytes (PEL) and M phi. After selection of PEL from animals immunized with ovalbumin by culture on specific antigen-pulsed syngeneic M phi, recovered T cells (selected PEL) are 75 to 95% Ia+ by both cytotoxicity and immunofluorescent analysis on the FACS using alloantisera to Ia from guinea pigs or mice. The subunit structure of the Ia molecules on T cells is similar to that of Ia molecules obtained from B cells, as determined by radiolabeling, immunoprecipitation, and analysis of gels. Incorporation of labeled amino acids into Ia by selected PEL was shown to be due to T cells because of the lack of effect of depletion of Ig+ cells, the elimination of incorporation with a monoclonal anti-lymphocyte antibody, and the negligible increase in radioactive Ia after addition of large numbers of peritoneal exudate M phi. Furthermore, when F1 (2 x 3) PEL are selected on parental M phi, the selected PEL express both parental (2 and 13) Ia specificities, which suggests that the Ia molecules are not adsorbed by T cells after their release by M phi. Evidence that synthesis by splenocytes is due to B cells was obtained by the results of deletion experiments with alpha Ig and C. Similarly, synthesis of Ia by populations of pulmonary alveolar M phi, which contain greater than 98% M phi as judged by morphology, adherence, and latex ingestion, was demonstrated to be due to M phi because of the lack of effect of removing T and B cells.


Transition in Longgu Surface Associated with Decoction Process of Keishikaryukotsuboreito.
We aim to attain the sustainable use of longgu and have investigated the significance of longgu in Keishikaryukotsuboreito (KRB) decoction. We have already reported that longgu alters compound profiles in KRB decoction and hypothesized that it does so by adsorbing foreign organic compounds into its superficial pores. In the present study, we focused on the adsorbability of organic materials onto longgu surface as the cause of component profile alteration. We analyzed the physical changes in longgu through the decoction process by measuring the adsorbed water on longgu surface. 1H magic angle spinning NMR (1H-MASNMR) spectroscopic analysis revealed that raw longgu (R-raw) as well as decocted longgu [whether single (R-r) or KRB (R-krb) decoction] adsorbed water. However, the amount of adsorbed water in R-krb was smaller than that in R-raw and R-r. The nitrogen adsorption isotherms of longgu samples indicated that longgu was macroporous. The Brunauer-Emmett-Teller (BET) surface area of R-krb was smaller than that of R-raw and R-r. Further, thermogravimetric analysis of longgu samples showed that R-krb adsorbed matter that R-raw and R-r did not adsorb. The above findings and the 1H-MASNMR analysis of heated longgu samples suggested that longgu adsorbed organic compounds into the pores. We considered that longgu adsorbed organic compounds during KRB decoction into its superficial pores through the decoction process.


Sexual healing: caring for patients recovering from myocardial infarction.
Sexuality is rarely addressed when patients are recovering from myocardial infarction (MI). This article discusses both nurses' and patients' attitudes to sexuality, and examines ways to increase nurses' awareness so that they can offer sexual advice and apply a truly holistic approach when caring for patients following an MI.


No signs of check-list fatigue - introducing the StOP? intra-operative briefing enhances the quality of an established pre-operative briefing in a pre-post intervention study.
The team timeout (TTO) is a safety checklist to be performed by the surgical team prior to incision. Exchange of critical information is, however, important not only before but also during an operation and members of surgical teams frequently feel insufficiently informed by the operating surgeon about the ongoing procedure. To improve the exchange of critical information during surgery, the StOP?-protocol was developed: At appropriate moments during the procedure, the leading surgeon briefly interrupts the operation and informs the team about the current Status (St) and next steps/objectives (O) of the operation, as well as possible Problems (P), and encourages questions of other team members (?). The StOP?-protocol draws attention to the team. Anticipating the occurrence of StOP?-protocols may support awareness of team processes and quality issues from the beginning and thus support other interventions such as the TTO; however, it also may signal an additional demand and contribute to a phenomenon akin to "checklist fatigue." We investigated if, and how, the introduction of the StOP?-protocol influenced TTO quality. This was a prospective intervention study employing a pre-post design. In the visceral surgical departments of two university hospitals and one urban hospital the quality of 356 timeouts (out of 371 included operation) was assessed by external observers before (154) and after (202) the introduction of the StOP?-briefing. Timeout quality was rated in terms of timeout completeness (number of checklist items mentioned) and timeout quality (engagement, pace, social atmosphere, noise). As compared to the baseline, after the implementation of the StOP?-protocol, observed timeouts had higher completeness ratings (F = 8.69, p = 0.003) and were rated by observers as higher in engagement (F = 13.48, p < 0.001), less rushed (F = 14.85, p < 0.001), in a better social atmosphere (F = 5.83, p < 0.016) and less noisy (F = 5.35, p < 0.022). Aspects of TTO are affected by the anticipation of StOP?-protocols. However, rather than harming the timeout goals by inducing "checklist fatigue," it increases completeness and quality of the team timeout.


Voltammetric aptasensor for thrombin by using a gold microelectrode modified with graphene oxide decorated with silver nanoparticles.
A sensitive electrochemical aptasensor was developed for the determination of thrombin. It is based on signal amplification by using graphene oxide (GO) decorated with silver nanoparticles (AgNP) and placed on a microelectrode. The graphene oxide decorated with silver nanoparticles (AgNP-GO) was synthesized by chemical reduction and then modified with a thrombin-binding aptamer 1 (TBA1; a 29-mer) carrying a 3'-terminal thiol group. It was immobilized on the AgNP-GO by self-assembled monolayer technique to form the signaling probe (TBA1-AgNP-GO). A capture thrombin-binding aptamer 2 (TBA-2; a 15-mer) carrying a 3'-terminal thiol group was self-assembled onto the surface of the gold electrode. After binding of thrombin and the signaling probe, a sandwich of type TBA2-thrombin-TBA1-AgNP-GO is formed. The square wave voltammetric signal of the AgNP is then recorded. The electrochemical oxidation signal (measured at 0.21 V vs. Ag/AgCl) increases linearly with the concentration of thrombin in the range from 0.05 nmol·L-1 to 5 nmol·L-1 with a detection limit of 0.03 nmol·L-1 (at S/N = 3). The aptasensor is highly specific and not affected by other proteins. It was successfully applied to the determination of thrombin in spiked human serum samples. Graphical abstract A sensitive electrochemical aptasensor for thrombin was developed based on the signal amplification of silver nanoparticles decorated graphene oxide at an ultramicroelectrode.


A computational modeling approach on three-digit number processing.
Recent findings indicate that the constituting digits of multi-digit numbers are processed, decomposed into units, tens, and so on, rather than integrated into one entity. This is suggested by interfering effects of unit digit processing on two-digit number comparison. In the present study, we extended the computational model for two-digit number magnitude comparison of Moeller, Huber, Nuerk, and Willmes (2011a) to the case of three-digit number comparison (e.g., 371_826). In a second step, we evaluated how hundred-decade and hundred-unit compatibility effects were moderated by varying the percentage of within-hundred (e.g., 539_582) and within-hundred-and-decade filler items (e.g., 483_489). From the results we predict that numerical distance as well as compatibility effects should indeed be modulated by the relevance of tens and units in three-digit number magnitude comparison: While in particular the hundred distance effect should decrease, we predict hundred-decade and hundred-unit compatibility effects to increase with the relevance of tens and units.


Evaluation of 5-hydroxytryptophol and other endogenous serotonin (5-hydroxytryptamine) analogs as substrates for UDP-glucuronosyltransferase 1A6.
Serotonin is a specific in vitro substrate for human UDP-glucuronosyltransferase (UGT) 1A6. In this study, the contribution of UGT1A6 to the glucuronidation of endogenous structural analogs of serotonin, including 5-hydroxytryptophol, N-acetylserotonin, and 6-hydroxymelatonin, was evaluated using available recombinant human UGT isoforms, human liver microsomes, and liver microsomes from animals that do not express functional UGT1A6 (Gunn rats and cats). Only UGT1A6 and UGT1A9 were found to glucuronidate 5-hydroxytryptophol at a concentration of 2 mM, although the glucuronidation rate with UGT1A6 was over 10 times that of UGT1A9. K(m) values for human liver microsomes (156, 141, and 134 microM) were most similar to that of expressed UGT1A6 (135 microM) but vastly different from that of UGT1A9 (3674 microM). 5-Hydroxytryptophol glucuronidation by human liver microsomes (n = 54) correlated well with serotonin glucuronidation (R(s) = 0.83) and UGT1A6 protein content (R(s) = 0.85). 5-Hydroxytryptophol also competitively inhibited serotonin glucuronidation by human liver microsomes (K(i) = 291 microM) and UGT1A6 (K(i) = 200 microM). N-acetylserotonin was glucuronidated most extensively by UGT1A6, although UGT1A9 and UGT1A10 showed moderate catalysis. 6-Hydroxymelatonin was glucuronidated largely by UGT1A9 and UGT1A10 but not at all by UGT1A6. Gunn rat liver glucuronidation rates for serotonin, 5-hydroxytryptophol, N-acetylserotonin, and 6-hydroxymelatonin were 11, 5, 32, and 3%, respectively, of that of normal rat liver. Cat liver microsomes did not glucuronidate serotonin, whereas relatively low activities were observed for the other indole substrates. In conclusion, these results indicate that human UGT1A6 plays a predominant role in the glucuronidation of 5-hydroxytryptophol and N-acetylserotonin, whereas 6-hydroxymelatonin is not a substrate for this enzyme.


Acute hemorrhagic edema of childhood (AHE)
Four patients with acute hemorrhagic edema (AHE) of childhood are presented. Two patients had associated pulmonary tuberculosis. AHE of childhood is a benign condition, characterized by inflammatory edema and ecchymotic purpura in a target or cockade pattern. Histology of the skin lesions shows typical leucocytoclastic vasculitis and the condition has therefore been considered a variant of Henoch-Schönlein purpura (HSP). However, because of its benign course, AHE should be considered as a separate entity.


Design of a compact synchrotron light source for medical applications at NIRS.
A synchrotron light source dedicated to medical applications is required to be compact for installation in limited spaces at hospitals. The NIRS storage ring, with a circumference of 44.8 m, is designed to accelerate electrons up to 1.8 GeV and to store a beam of 400 mA. The ring is composed of superconducting bending magnets for downsizing. A beam of 300 MeV is injected into the ring from a microtron operated at an L-band RF frequency. There are two superconducting multipole wigglers with nine poles and a maximum field of 8 T, which can produce a photon flux of about 1.4 x 10(13) photons s(-1) mrad(-1) (0.1% bandwidth)(-1) at 33 keV used for coronary angiography.


Screening for Prediabetes and Type 2 Diabetes: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.
Type 2 diabetes is common and is a leading cause of morbidity and disability. To review the evidence on screening for prediabetes and diabetes to inform the US Preventive Services Task Force (USPSTF). PubMed/MEDLINE, Cochrane Library, and trial registries through September 2019; references; and experts; literature surveillance through May 21, 2021. English-language controlled studies evaluating screening or interventions for prediabetes or diabetes that was screen detected or recently diagnosed. Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings; meta-analyses conducted when at least 3 similar studies were available. Mortality, cardiovascular morbidity, diabetes-related morbidity, development of diabetes, quality of life, and harms. The review included 89 publications (N = 68 882). Two randomized clinical trials (RCTs) (25 120 participants) found no significant difference between screening and control groups for all-cause or cause-specific mortality at 10 years. For harms (eg, anxiety or worry), the trials reported no significant differences between screening and control groups. For recently diagnosed (not screen-detected) diabetes, 5 RCTs (5138 participants) were included. In the UK Prospective Diabetes Study, health outcomes were improved with intensive glucose control with sulfonylureas or insulin. For example, for all-cause mortality the relative risk (RR) was 0.87 (95% CI, 0.79 to 0.96) over 20 years (10-year posttrial assessment). For overweight persons, intensive glucose control with metformin improved health outcomes at the 10-year follow-up (eg, all-cause mortality: RR, 0.64 [95% CI, 0.45 to 0.91]), and benefits were maintained longer term. Lifestyle interventions (most involving >360 minutes) for obese or overweight persons with prediabetes were associated with reductions in the incidence of diabetes (23 RCTs; pooled RR, 0.78 [95% CI, 0.69 to 0.88]). Lifestyle interventions were also associated with improved intermediate outcomes, such as reduced weight, body mass index, systolic blood pressure, and diastolic blood pressure (pooled weighted mean difference, -1.7 mm Hg [95% CI, -2.6 to -0.8] and -1.2 mm Hg [95% CI, -2.0 to -0.4], respectively). Metformin was associated with a significant reduction in diabetes incidence (pooled RR, 0.73 [95% CI, 0.64 to 0.83]) and reduction in weight and body mass index. Trials of screening for diabetes found no significant mortality benefit but had insufficient data to assess other health outcomes; evidence on harms of screening was limited. For persons with recently diagnosed (not screen-detected) diabetes, interventions improved health outcomes; for obese or overweight persons with prediabetes, interventions were associated with reduced incidence of diabetes and improvement in other intermediate outcomes.


Close distal margin is associated with locoregional rectal cancer recurrence: A multicenter study.
The importance of the radial margin for rectal cancer resection is well understood. However, surgeons have deemphasized the distal margin, accepting very close distal margins to perform sphincter-preserving surgery. We hypothesized that distal margins < 1 cm would be an independent risk factor for locoregional recurrence. The objective was to determine whether close distal margins are associated with increased locoregional recurrence risk. This was a multi-institutional retrospective cohort study conducted at six academic medical centers including patients who received low anterior resection surgery for primary rectal cancer between 2007 and 2018. Of 556 low anterior resection patients, the rate of close distal margin was 12.8% (n = 71), and the locoregional recurrence rate was 5.0% (n = 28). The locoregional recurrence rate for close distal margin cases was 9.9% (n = 7) compared to 4.3% (n = 21) for distal margins ≥1.0 cm. In multivariable analysis, the only factor significantly associated with locoregional recurrence was close distal margin (adjusted odds ratio: 2.80, confidence interval: 1.08-7.25, p = 0.035). Rectal cancer patients with close distal margins (<1 cm) following low anterior resection had a significantly higher risk for locoregional recurrence. Therefore, the decision to perform low anterior resection with margins < 1 cm should be taken with caution.


Patterns of stress response and tolerance based on transcriptome profiling of rice crown tissue under zinc deficiency.
Zinc (Zn) deficiency is the most prevalent micronutrient disorder in rice and leads to delayed development and decreased yield. Several studies have investigated how rice plants respond to Zn deficiency and examined the differences between Zn-efficient (ZE) and Zn-inefficient (ZI) genotypes. ZE genotypes reallocate more Zn to roots and are better at maintaining crown root development than ZI genotypes in response to Zn deficiency. However, little is known about the molecular mechanisms controlling these differences. Moreover, the role of the crown, the part of the stem from which crown roots emerge, has yet to be examined. In this study we highlight the molecular mechanisms triggered by early Zn deficiency in crown tissue through RNA sequencing of two contrasting groups of several ZE and ZI genotypes. This method allowed us to (i) identify several novel and well-known Zn transporters involved in Zn retranslocation from the crown to the shoot and roots in response to Zn deficiency; (ii) determine that Zn deficiency triggers the conversion of soluble sugars into starch; and (iii) detect several candidate genes possibly conferring Zn efficiency, including a monosaccharide transporter, a Zn finger domain-containing protein, a gibberellin-stimulated family protein and a plasma membrane polypeptide family protein.


Prediction of genetic gain in finite populations with heterogeneous predicted breeding values accuracies.
The algebraic expression of the genetic selection differential (expected genetic superiority of breeders after a selection on their Predicted Breeding Values) was derived when a limited number of individuals were selected from a limited sample of candidates on the basis of their predicted genetic value, with heterogeneous reliabilities. A formula is proposed for situations in which these reliabilities can be clustered in a few classes. We show that the expected genetic selection differential increases with the number of classes, the mean reliability being constant. In the panel of cases simulated, this increase reached up to 18% of the values obtained in the homogeneous situation. We used the proposed formulae to estimate selection differentials and compared it numerically with performing simulations. In terms of speed of computation, our algebraic formulae performed better than simulations in populations of limited size.


On the movement toward psychotherapy integration : the case of panic disorder.
The prospect of using psychotherapy integration to enhance therapeutic efficacy increases as clinical discussion and empirical inquiry mount. The authors review briefly the historical origins of integrative thought, discuss the new receptivity with which it is being met, and examine the clinical use of an integrative framework, using progress in the treatment of panic disorder as an example of the potential of integrative treatment strategies.


Expressions of SE-1, CD31 and CD105 in the vascular endothelial cells and serum of rat with hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide. In order to investigate the molecular biologic mechanism of HCC's development, we studied the expressions of SE-1, CD105 and CD31 in tumor endothelial cells (TECs) of HCC and in the serum of rats. We analyzed the expressions of SE-1, CD31 and CD105 in rat HCC tumor tissues using immunohistochemistry (IHC). Twenty HCC bearing rats and eighteen normal rats were examined for the expressions of SE-1, CD31 and CD105 antigens in serum by enzyme-linked immunosorbent assay (ELISA). SE-1, CD31 and CD105 antigens were detected both in HCC tissue and in normal liver tissue with higher expressions of CD31 and CD105 in HCC while the SE-1 antigen expression was higher in normal liver. Similarly, serum CD31 and CD105 in rats with HCC were significantly increased compared with normal rats (t = 2.8628, P = 0.0086; t = 4.4922, P < 0.0001, respectively). In contrast, SE-1 antigen in HCC rat serum was significantly decreased compared with normal rats (t = 3.4983, P = 0.0011). SE-1, CD31 and CD105 are closely related with liver tumor angiogenesis, which is similar to their performances in terms of their expressions in the serum.


[Nutritional physiology effect of dietary fats in the diet of growing pigs. 1. Effect of an isocaloric exchange of carbohydrate energy compared with fat energy on protein retention, in vitro synthesis of fat from glucose and on several blood parameters in piglets].
Three groups of male, castrated piglets of the German Landrace breed, weight range 3-30 kg, were used to study the relation between fattening performance and blood parameters when feeding rations containing different amounts of fat. The fat content of the rations was either 5% (group I), 18% (group II) or 35% (group III). Concomitantly with the increased metabolizable energy (ME) content of the ration the content of digestible protein (DP) was increased and the amount of feed reduced in order to guarantee an equal intake of ME and DP in all three groups. The digestibility of the crude nutrients and protein retention of the subjects were determined in nine subsequent trials each lasting 7 days. At a body weight of 27 kg the blood concentrations of insulin, glucose, free fatty acids, neutral lipids and cholesterol were determined at different times after feeding. In addition, an oral glucose tolerance test was made and the in-vitro synthesis of fat from glucose was measured. The apparent digestibility of fat amounted, unexpectedly, to approximately 94% on the high rat rations II and III. In all groups a significant positive relation between body weight and digestibility of the fat was determined. Despite equal daily intakes of ME in all groups, in group III daily weight gain and protein retention were 7% (p less than 0.01) and 4% (p less than 0.01) higher than in group I, respectively. Blood urea levels of group III were 67% (p less than 0.01) lower than in group I. The mean daily nitrogen retention of the three groups rose gradually from 4 g at a body weight of 5 kg to 16-17 g at a body weight of 25 kg. The feed conversion of group I was lower by 22 and 36% as compared to groups II and III, respectively. Highly significant differences were observed among either groups (p less than 0.01). It has been calculated that in group III the consumption of ME/kg weight gain was about 8% (p less than 0.05) lower than in the two other groups. According to the increased fat percentage of the rations, body protein content diminished from 17,1% in group I to 16,5 and 16% in groups II and III, respectively. Only the difference between groups I and III proved to be significant (p less than 0.05). In group I feed intake resulted in an increase in the insulin level by 55% (p less than 0.05) whereas glucose did not change significantly.(ABSTRACT TRUNCATED AT 400 WORDS)


Nontargeted Screening of Water Samples Using Data-Dependent Acquisition with Similar Partition Searching.
A rapid screening method for the detection of nontargeted compounds in surface water samples was developed using MS-MS high-resolution mass spectrometry and data-dependent acquisition. The key parameters for the acquisition method were optimized using five model compounds with diverse chemical characteristics. The parameter selection required optimization between the total number of precursor ions that could be selected in an LC-MS run, the quality of each MS (full range) spectrum, and the quality of each MS-MS fragmentation spectrum. After the acquisition method was optimized, 18 surface water samples from rivers, reservoirs, and effluents from wastewater treatment plants were analyzed, generating 41625 MS-MS spectra in about 14 h. The raw data were then converted into two generic formats using the open-access program MSConvert. A combinatorial approach, similar partition searching (SPS), was then used to putatively identify analytes from the accurate mass of each analyte (adjusted for the adduct mass) and the corresponding MS-MS spectra were obtained. In this approach, the structures of about 250000 common compounds, stored in a large database as mathematical partitions of their exact mass, were compared directly to each MS-MS spectrum. Compounds with a similar mass and retention time were grouped together and labeled as "Analytes", using an Excel Add-In. The isotope ratio data from the MS spectrum, the corresponding MS-MS spectra, and the putative identifications were then imported into an Access relational database to facilitate sorting, searching, filtering, and querying the results. This allowed final inspection to assess confidence of the identifications made through the nontargeted screening.


Differential regulation of hypothalamic pituitary corticotropin releasing hormone receptors during development of adjuvant-induced arthritis in the rat.
The expression of corticotropin releasing hormone (CRH) in the hypothalamic paraventricular nucleus (PVN) and CRH receptor mRNA in the PVN and anterior pituitary was studied during development of adjuvant-induced arthritis in Piebald-Viral-Glaxo rats, using in situ hybridization techniques. As previously shown with i.p. hypertonic saline injection, basal and immobilization stress-stimulated CRH mRNA levels in the PVN were significantly lower than in controls 14 days after adjuvant injection. However, 7 days after injection, preceding the onset of inflammation, the increase of CRH mRNA following immobilization was significantly higher than in control rats. In contrast to other chronic stress paradigms, inflammation stress failed to induce type-1 CRH receptor (CRH-R1) mRNA in the PVN, either at 7 days, or at 14 days after adjuvant injection, when inflammation is present. The ability of acute immobilization to induce CRH-R1 mRNA in the PVN was not affected 14 days after adjuvant injection but parallel to the CRH peptide mRNA response it was markedly potentiated at 7 days. Pro-opiomelanocorpin (POMC) mRNA levels in the anterior pituitary increased significantly 14 days after adjuvant injection, and they were unaffected by 1 h immobilization. While CRH binding in the pituitary decreased significantly 14 days after adjuvant injection, CRH-R1 mRNA was unchanged. This study shows biphasic hypothalamic responses to acute stress during development of adjuvant-induced arthritis, with enhanced CRH peptide and CRH-R1 mRNAs responses at 7 days, preceding the onset of inflammation, and blunted CRH mRNA responses at 14 days at the height of the inflammatory response. The lack of CRH receptor expression in the PVN in this model of chronic inflammation stress associated to low hypothalamic CRH peptide levels supports the view that positive feedback regulation by CRH is necessary to maintain enhanced CRH expression during chronic stress.


Radiological Imaging in Nail Unit Disorders (Part I) - Modalities Used.
The nail unit is a unique skin appendage, capable of mounting only a limited number of reaction patterns to a variety of insults. This makes it difficult to diagnose many nail conditions based on clinical features alone. Thus, diagnostic modalities have an important role to play in nail disorders. Emphasis is placed on non-invasive diagnostic methods, of which, radiological imaging forms an important part; however, it is a field largely under-explored with very few studies and reports available in the literature. This could be due to the problems encountered in nail unit radiology including its small size, complex anatomy, requirement for special high-frequency probes to reliably evaluate superficial structures, and non-familiarity with nail unit radiological features even amongst trained radiologists. Nevertheless, it plays a useful role in diagnosing nail disorders (especially tumors), localizing the changes, exploring differential diagnoses, estimating prognosis, and planning management. This article is aimed at collating scientific data pertaining to various radiological modalities used in the diagnosis of nail diseases. The advantages and limitations of various imaging techniques used for evaluating the nail unit, including digital radiographs, high-frequency ultrasound, ultrasound doppler (USD), computed tomography (CT), and magnetic resonance imaging (MRI), are discussed in the first part. The second part will discuss the features of common and uncommon nail diseases.


A unique dicentric X;Y translocation with Xq and Yp breakpoints: cytogenetic and molecular studies.
A 32-year-old woman presented with secondary amenorrhea and infertility. She was of normal height and her breasts were well developed, but she had streak gonads; there were no signs of virilization, and she showed no somatic stigmata of Turner syndrome. Chromosome analysis revealed a dicentric X;Y translocation with Xq and Yp breakpoints. Centromeric banding demonstrated a Y centromere and a "suppressed" X centromere. The karyotype of the patient was interpreted as 46,X,t(X;Y)(q22;p11). The Yp breakpoint was confirmed by DNA-hybridization studies with six probes detecting Y-specific sequences. These DNA-hybridization studies were consistent with the presence of the long arm, centromere, and much of the proximal short arm of the Y. The Y-DNA studies of this female also revealed the absence of the distal short arm of the Y chromosome, to which the testis-determining factor has previously been localized.


Poly[di-μ-aqua-diaqua-di-μ(6)-malonato-cobalt(II)dipotassium(I)].
In the title complex, [CoK(2)(C(3)H(2)O(4))(2)(H(2)O)(4)](n), the Co atom is located on a position with site symmetry 2/m, the K atom and one water mol-ecule are located on a mirror plane, and the malonate and one water mol-ecule are located on a twofold rotation axis. The K(I) atom is seven-coordinated by four carboxyl-ate O atoms from four malonate ligands and by three water O atoms, forming a distorted polyhedron. The Co(II) atom is in an almost octa-hedral environment formed by four carboxyl-ate O atoms from two malonate ligands and two water O atoms. The structure consists of layers parallel to (20[Formula: see text]) built up from edge-sharing KO(7) and CoO(6) polyhedra, which are connected by O-H⋯O hydrogen bonding including water mol-ecules into a three-dimensional network.


[Cataract in children after autologous bone marrow transplantation. A common, but curable complication].
Bone marrow transplantation (BMT) is an established treatment of hematological malignancies in children. With a rapidly increasing number of long-term survivors, more attention is focused on late sequelae to this therapy. Several cataractogenic factors are involved in BMT, such as ionizing irradiation, corticosteroid treatment, and chemotherapeutic agents. Lens opacity is therefore a potential late side-effect of BMT. The incidence and degree of cataract in 29 children who had undergone autologous or syngeneic BMT were recorded. Median follow-up was eight years (4-10 years). 21 children had received total body irradiation prior to BMT; they all developed cataract of the posterior subcapsular type after three years (median). Six children needed surgical repair in the form of intraocular lens implantation after extracapsular cataract extraction.


Electrocatalytic degradation of sulfamethylthiadiazole by GAC@Ni/Fe three-dimensional particle electrode.
In this work, GAC@Ni/Fe particle electrodes were prepared and employed for the degradation of sulfamethylthiadiazole (SMT) by three-dimensional electrocatalytic technology. The effects of particle electrode bi-metal loading ratio, cell voltage, particle electrode dosage, electrode plate spacing, and SMT initial concentration on SMT removal were studied. In addition, GAC@Ni/Fe particle electrode was analyzed by the scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffractometer (XRD), X-ray photoelectron spectrometer (XPS), and Fourier transform infrared spectrometer (FTIR) to characterize which indicated that a significant amount of iron-nickel oxide was formed on the surface of GAC@Ni/Fe particle electrode. The results indicated that when the nickel-iron loading ratio is 1:1, the SMT removal effect is the best, and the removal rate can reach 90.89% within 30 min. Compared with the granular activated carbon without bimetal, the removal efficiency is increased by 37.58%. The degradation of SMT in the GAC@Ni/Fe particle three-dimensional electrode reactor is the joint result of both direct oxidation and indirect oxidation. The contribution rates of direct oxidation of anode and particle electrode and indirect oxidation of ·OH in the degradation are 32%, 27%, and 41%, respectively. Based on the intermediate detected by ultra-high liquid chromatography and the calculation of bond energy of SMT molecule by Gauss software, the degradation pathway of SMT in the GAC@Ni/Fe three-dimensional electrode reactor is proposed. This research provides a green, healthy, and effective method for removing sulfonamide micro-polluted wastewater.