Methodologic considerations for research in traditional (alternative) medicine.
The widepsread use, in the United States and other western countries, of alternative medical practices often derived from traditional systems of health has intensified the need to evaluate their safety and effectiveness. These practices tend to generate polarized attitudes of either acceptance or rejections. Opponents reject them because, they claim, good scientific research has not supported their use. Proponents insist that current scientific methodologies are not appropriate to evaluate these practices. This article briefly examines these issue, suggesting that the answer lies between these 2 extreme positions. Various methodologic issues are considered, and suggestions are made to adapt scientific methodology, where appropriate, to respect the particularities of alternative medicine.


Motor outcomes after neonatal arterial ischemic stroke related to early MRI data in a prospective study.
We aimed to correlate early imaging data with motor outcomes in a large, homogeneous, cohort of infants with neonatal (diagnosed before 29 days of life) arterial ischemic stroke (AIS). From a prospective cohort of 100 children with neonatal AIS, we analyzed the MRI studies performed within the 28 first days of life for 80 infants evaluated at 2 years of age. The relationships between infarction location and corticospinal tract (CST) involvement and motor outcomes were studied Seventy-three infarctions involved the middle cerebral artery (MCA) territory. Of those, 50 were superficial infarctions, 5 deep infarctions, and 18 mixed infarctions. The CST was involved in 24 cases. Nineteen patients with MCA infarctions (26% [95% confidence interval: 16%-34%]) developed hemiplegia. Mixed infarctions (P<.0001) and CST involvement (P<.0001) were highly predictive of hemiplegia. In contrast, 88% of children with isolated superficial MCA infarctions did not exhibit impairment. Accurate prediction of motor outcomes can be obtained from early MRI scans after neonatal AIS. The absence of involvement of the CST resulted in normal motor development in 94% of cases. CST involvement resulted in congenital hemiplegia in 66% of cases.


Dynamic changes in soluble suppression of tumorigenicity 2 levels predict major adverse cardiovascular events in patients with ST‑segment elevation myocardial infarction.
Introduction:The predictive value of soluble suppression of tumorigenicity 2 (sST2) for the occurrence of major adverse cardiovascular events (MACEs) in patients with ST‑segment elevation myocardial infarction (STEMI) remains unclear. We aimed to investigate the role of sST2 in predicting MACEs in STEMI patients after primary percutaneous coronary intervention (pPCI). A total of 350 patients were enrolled in this study. The levels of sST2, N‑terminal pro-B‑type natriuretic peptide (NT‑proBNP), cardiac troponin I (TnI), and creatine kinase-MB (CK‑MB) were measured on admission as well as 24 hours and 5 days after pPCI. The end point was the incidence of MACEs. Compared with the values on admission, sST2 levels increased 24 hours post pPCI and decreased significantly at day 5 after the procedure in the whole cohort. The pattern of sST2 level changes between the 3 time points was similar in the MACE and MACE‑free groups. Notably, the change in the sST2 level from admission to 24 hours post pPCI (Δ1sST2) was significantly higher in the MACE group. After multivariable adjustment, Δ1sST2 was an independent risk factor for MACEs, with an area under the curve of 0.621 (95% CI, 0.547-0.695). Patients with a greater Δ1sST2 had a significantly higher incidence of composite MACEs, coronary revascularization, and cardiac rehospitalization. However, the change in sST2 levels from admission to 5 days post pPCI, as well as the dynamic changes in NT‑proBNP, TnI, and CK‑MB levels had no predictive value. The increase in plasma sST2 levels from admission to 24 hours post pPCI has a potential value for independently predicting the incidence of coronary revascularization and cardiac rehospitalization at 1 year in patients with STEMI.


Osteogenicity of titanium implants coated with calcium phosphate or collagen type-I in osteoporotic rats.
This study hypothesized that modification of titanium implant surface, e.g. by the deposition of inorganic/organic coatings, can significantly improve the implant-bone response compared in osteoporotic vs. healthy conditions. After osteoporosis was induced in 15 female Wistar rats by ovariectomy (OVX) and confirmed by in vivo micro-CT analysis, implants coated with calcium phosphate (CaP) or collagen type-I and non-coated implants were placed into bilateral femoral condyles. Another 15 sham-operated rats served as controls. Twelve weeks after implantation, micro-CT bone volume (%BV) and histomorphometrical bone area (%BA) were lower around control implants in osteoporotic rats (BV = 60.4%, BA = 43.8%) compared to sham-operated rats (BV = 74.0%, BA = 62.0%). Interestingly, CaP and collagen type-I surface coatings enhanced bone-to-implant contact (%BIC) compared to non-coated implants in osteoporosis (51.9%, 58.2%) as well as in sham-operated (69.7%, 64.4%) groups. The study confirmed that an osteoporotic condition has a significant effect on the amount of bone present in close vicinity to implants. Evidently, the use of osteogenic surface coatings has a favorable effect on the bone implant interface in both osteoporotic and sham-operated conditions.


Orbital Hydatid Cyst Causing Papilledema and Proptosis in an Adult.
Hydatid cyst is an infectious disease caused by Echinococcus granulosus, primarily involving the liver and lungs. The orbit is an extremely rare site for involvement with hydatid cyst. We present a 36-year-old man with unilateral visual loss, proptosis, and papilledema caused by an orbital hydatid cyst.


Generation and characterization of Csrp1 enhancer-driven tissue-restricted Cre-recombinase mice.
Cell type-specific genetic modification using the LoxP/Cre system is a powerful tool for genetic analysis of distinct cell lineages. Because of the unique arterial smooth muscle-restricted expression of a 5.0 kb cysteine-rich protein (Csrp1) enhancer (Lilly et al.,2001, Dev Biol 240:531-547), we hypothesized that a transgenic Cre line would prove useful for the smooth muscle lineage-specific genetic manipulation. Here we describe a transgenic mouse line, ECsrp1(Cre), where Cre is initially specifically expressed in arterial smooth muscle cells. Use of the ROSA26R reporter allele confirmed that Cre-mediated recombination in vascular smooth muscle cells began at approximately E10.0 and was highly proficient. Subsequently, Cre is expressed in restricted skeletal and nonvascular smooth muscle lineages. This lineage tracing data is important for future conditional knockout studies to understand where and when Cre-mediated deletion occurs and where Cre-expressing daughter cells finally localize. Additionally, we crossed the ECsrp1(Cre) mice to the ROSA26(-eGFP-DTA) diphtheria toxin A-expressing mice to genetically ablate ECsrp1(Cre) expressing cells. This ECsrp1(Cre) transgenic line should thus prove useful for genetic analysis of diverse aspects of cardiovascular morphogenesis and as a general smooth muscle lineage deletor line.


Tribenuron-methyl-resistant Descurainia sophia L. exhibits negative cross-resistance to imazethapyr conferred by a Pro197Ser mutation in acetolactate synthase and reduced metabolism.
Descurainia sophia L. is one of the most notorious weeds infesting winter wheat in China. Mutations at Pro197 in acetolactate synthase (ALS) results in resistance of D. sophia to tribenuron-methyl and cross-resistance to many ALS inhibitors. Negative cross-resistance to imazethapyr was observed in tribenuron-methyl-resistant (TR) D. sophia with the Pro197Ser mutation in a previous study. In the present research, another TR D. sophia with the Pro197Ser mutation was obtained. To explore the mechanisms of negative cross-resistance, the ALS sensitivity, the absorption and metabolism of imazethapyr in tribenuron-methyl-susceptible (TS) and TR D. sophia were studied. The TR D. sophia population with the Pro197Ser mutation (pHB23) displayed negative cross-resistance to imazethapyr and no cross-resistance to imazamox and imazapic. In contrast, TR D. sophia populations with other Pro197 mutations had no or low resistance to imazethapyr. The ALS in the pHB23 population was more susceptible to imazethapyr than that in the TS population. There was no difference in the absorption of imazethapyr, imazamox, and imazapic between TS and pHB23 plants. However, the metabolism of imazethapyr in TS D. sophia was faster than that in pHB23 plants up to 1 week after treatment. There was no significant difference in the metabolism of imazamox and imazapic between TS and pHB23 plants. The TR D. sophia population with the Pro197Ser mutation exhibited negative cross-resistance to imazethapyr, which was likely due to reduced metabolism and increased sensitivity of ALS to imazethapyr. © 2021 Society of Chemical Industry.


Hypopituitarism after radiotherapy for extracranial head and neck cancers.
The purpose of this study was to investigate the incidence of radiotherapy-induced primary and secondary hypopituitarism. Three hundred twelve patients treated with radiotherapy for extracranial head and neck tumors between 1964 and 2000 were evaluated. Radiotherapy doses to the hypothalamus and pituitary were estimated by reconstructing treatment plans. Clinical hypopituitarism was observed in 44 (14.1%) patients after a median interval of 5.6 years. Hypothalamic dysfunction was reported in 14 patients after a median interval of 4.4 years. Neither fractionation nor adjuvant chemotherapy significantly impacted clinical hypopituitarism on multivariate analysis, but total dose to the pituitary was significant (p = .0228). Twenty-three of 68 (33.8%) patients tested for hypopituitarism demonstrated subclinical hypopituitarism. The 5- and 10-year rates of freedom from clinical hypopituitarism were 93% and 72%. The 5- and 10-year rates of freedom from subclinical hypopituitarism were 85% and 65%. Clinical and subclinical manifestations of late radiation toxicity were observed in the hypothalamic-pituitary axis.


Increased plasma adiponectin concentrations in poorly controlled patients with phenylketonuria normalize with a strict diet: evidence for catecholamine-mediated adiponectin regulation and a complex effect of phenylketonuria diet on atherogenesis risk factors.
Adiponectin (Adpn), an adipose tissue-derived hormone, prevents endothelial inflammation and early atherogenesis. Classic phenylketonuria (PKU), an inborn error of phenylalanine (Phe) metabolism, results in a reduction of catecholamine biosynthesis and requires treatment with lifelong low-Phe diet to prevent mental dysfunction and allow proper intellectual development. In this study, we evaluated the effect of the quality of PKU diet on plasma Adpn concentrations and related biochemical indices of endothelial dysfunction and atherogenesis. Patients with PKU were divided into groups A (n = 18), who were on a strict diet, and B (n = 18), who were on a loose diet, after evaluation of their 30-day dietetic diaries and measurement of Phe blood concentrations. Twenty healthy children of similar ages and body mass indexes served as controls (group C). Group A patients had normal circulating catecholamines and Adpn and decreased tumor necrosis factor alpha concentrations and low-density lipoprotein cholesterol/apolipoprotein B ratio compared with groups B and C. Despite these favorable parameters, however, homocysteine concentration was twice as high in group A compared with groups B and C. Interestingly, group B patients under loose dietary control had significantly elevated Adpn concentrations compared with groups A and C and increased tumor necrosis factor alpha and an unfavorable lipid profile, but normal levels of homocysteine. These data support the hypothesis that catecholamines inhibit Adpn secretion and that the elevated Adpn of the poorly controlled patients might moderate their risk for endothelial dysfunction and atherogenesis. Homocysteine production appears to be unfavorably affected by a strict PKU diet, diverging from the rest of the atherogenesis risk factors, which were improved in the well-controlled patients.


Problem-based ACLS instruction: a model approach for undergraduate emergency medical education.
The optimal format for teaching advanced cardiac life support (ACLS) to medical students and other groups with little emergency medicine experience has not been studied extensively. We report an ACLS provider course that was taught to sophomore medical students using a self-directed, problem-based learning model. The traditional two-day provider course format was replaced by a series of clinical problems that emphasized various aspects of the ACLS curriculum. Students then met weekly with an ACLS instructor who served as a tutor to discuss the problem. A specific set of learning objectives for the entire ACLS curriculum was developed into a study unit index and given to students at the beginning of the course. Enhanced practice time was offered to students in the form of traditional teaching stations and skills laboratories. Students were tested using standard ACLS criteria. The students in the problem-based course achieved a higher pass rate on the written test and skills stations than senior medical students did in a standard two-day course during the same time period. The problem-based format with enhanced practice time would appear to be an effective alternative for groups that need to acquire the basic skills needed in a resuscitation attempt but have little previous experience in this area.


Kaempferol Identified by Zebrafish Assay and Fine Fractionations Strategy from Dysosma versipellis Inhibits Angiogenesis through VEGF and FGF Pathways.
Natural products are a rich resource for the discovery of therapeutic substances. By directly using 504 fine fractions from isolated traditional Chinese medicine plants, we performed a transgenic zebrafish based screen for anti-angiogenesis substances. One fraction, DYVE-D3, was found to inhibit the growth of intersegmental vessels in the zebrafish vasculature. Bioassay-guided isolation of DYVE-D3 indicates that the flavonoid kaempferol was the active substance. Kaempferol also inhibited the proliferation and migration of HUVECs in vitro. Furthermore, we found that kaempferol suppressed angiogenesis through inhibiting VEGFR2 expression, which can be enhanced by FGF inhibition. In summary, this study shows that the construction of fine fraction libraries allows efficient identification of active substances from natural products.


Histamine, leukotriene D4 and platelet-activating factor in guinea pig passive cutaneous anaphylaxis.
The involvement of histamine, leukotriene D4 (LTD4) and platelet-activating factor (PAF) in cutaneous anaphylaxis was investigated in a guinea pig model. When given alone, the H1 receptor antagonist chlorpheniramine, the LTD4/E4 antagonist LY171883 and the PAF antagonist WEB2086 were unable to inhibit increased microvascular plasma protein leakage in passive cutaneous anaphylaxis (PCA) reactions, as monitored by the extravasation of intravenously injected 125I-albumin. Furthermore the H2 receptor antagonist cimetidine and the serotonin antagonist methysergide were unable to reduce PCA responses when given alone or in combination with chlorpheniramine. In marked contrast, combinations of antagonists were able to reduce plasma leakage significantly. A combination of chlorpheniramine, LY171883 and WEB2086 virtually abolished plasma leakage during the PCA response, but did not influence the plasma protein leakage induced by intradermal injection of bradykinin. These results demonstrate that these allergic reactions involve several mediators and that the inability of an individual mediator antagonist to reduce responses does not necessarily rule out a role for that mediator.


Direct antiglobulin test negative autoimmune hemolytic anemia associated with autoimmune hepatitis.
A case of direct antiglobulin test(DAT)-negative autoimmune hemolytic anemia (AIHA) associated with autoimmune hepatitis (AIH) is presented. A 54-year-old female was admitted with liver dysfunction and anemia. AIH was diagnosed based on the diagnostic criteria of the International Autoimmune Hepatitis Group. The patient was DAT-negative, and exhibited all the clinical features of warm type AIHA and elevated levels of red blood cell-associated IgG. Marked improvement of subjective symptoms, the return to normal of hematological and liver test values, and a decrease in the level of RBC-associated IgG were observed after the start of corticosteroid therapy. Although an association of AIH and AIHA is rarely reported, the measurement of RBC-associated IgG is recommended in cases of AIH with DAT-negative anemia, as both disorders are autoimmune in nature.


Prediction of boron concentrations in blood from patients on boron neutron capture therapy.
In boron neutron capture therapy, blood boron concentration is the key factor to calculate radiation dose, however, blood sampling is difficult during neutron irradiation. The prediction of blood boron concentrations for BNCT treatment planning has been prospectively investigated using patient data obtained at first craniotomy after the infusion of a low dose of sodium undecahydroclosododecaborate. The boron biodistribution data showed a biexponential pharmacokinetic profile. If the final boron concentration at 6 or 9 hours after the end of the infusion is within the 95% confidence interval of the prediction, direct prediction from biexponential fit will reduce the error of blood boron concentrations during irradiation to around 6%. Actual boron concentrations during BNCT were reasonably and accurately predictable from the test data.


Bis(μ-pyridinium-2-carboxyl-ato-κO:O')bis-[triaqua-(sulfato-κO)manganese(II)].
The asymmetric unit of the title compound, [Mn(2)(SO(4))(2)(C(6)H(5)NO(2))(2)(H(2)O)(6)], comprises half of a centrosymmetric dimer. The Mn(II) atom is coordinated by two O atoms of the monodentate carboxyl-ate ligand, an O atom of the sulfate anion in axial position and three water mol-ecules in a distorted octa-hedral geometry. In the crystal, mol-ecules are connected through N-H⋯O and O-H⋯O hydrogen bonds, forming a three-dimensional network. The crystal structure is further stabilized by inter-molecular π-π inter-actions [centroid-centroid distance = 3.842 (2) Å].


A Genetic Etiology Identified for a Form of Familial Polyvalvular Dysplasia.
This case presents a family with multiple individuals diagnosed with congenital heart disease (CHD) secondary to a novel TAK1-binding protein 2 pathogenic variant. This case advocates the use of cardiovascular genetic testing in individuals with CHD as part of a comprehensive approach to managing infants with CHD. (Level of Difficulty: Advanced.).


Creativity in Parkinson's disease as a function of right versus left hemibody onset.
Creativity is heavily dependent on divergent thinking and divergent thinking appears to be strongly dependent on fontal lobe function. Since patients with Parkinson's disease (PD) often have evidence of frontal lobe dysfunction we wanted to learn if these patients have a reduction of creativity, as well as learning if the side of onset (right versus left) influences the type (verbal versus visuospatial) of decrement in creativity. Participants of this study were patients with right (RHO) or left (LHO) onset PD as well as matched controls. All subjects were given the Abbreviated Torrance Test of Creative Thinking for Adults (ATTA), a widely used test to assess creativity that examines Fluency, Originality, Flexibility and Elaboration. Subjects were also assessed with the Controlled Word Association Test (COWAT). When compared to controls the patients with RHO, but not LHO, had a decrease of verbal creative fluency. Patients with PD often have a decrease on the COWAT, but performance on the COWAT did not differ between the RHO and the LHO patients. This suggests that patients with PD who have RHO have a decrease in verbal creativity and this decrement does not appear to be related to decreased fluency.


Cisplatin plus weekly CPT-11/docetaxel in advanced esophagogastric cancer: a phase I study with pharmacogenetic assessment of XPD, XRCC3 and UGT1A1 polymorphisms.
A multicenter phase I trial to establish the recommended dose of CPT-11/docetaxel plus cisplatin in advanced esophagogastric cancer patients and to correlate the efficacy and toxicity with genetic polymorphisms in DNA repair genes (XPD and XRCC3) and the UGT1A1 gene. Four dose levels with a fixed dose of cisplatin (60 mg/m(2)), day 1, and dose-escalation of CPT-11 (50-70 mg/m(2)) and docetaxel (25-30 mg/m(2)), days 1 and 8, every 3 weeks were planned. Polymorphisms of XPD (Asp312Asn and Lys751Gln), XRCC3 (Thr241Met) and UGT1A1*28 were examined in baseline peripheral blood. Twenty-eight patients were included at three different dose levels. Dose-limiting toxicities were febrile neutropenia and diarrhea; the recommended dose was established at CPT-11 60 mg/m(2) and docetaxel 25 mg/m(2) plus cisplatin 60 mg/m(2). Objective response was observed in 13 patients (50%). Median time to progression was 6.6 months, and median survival was 11.3 months. Median time to progression was 9.7 months for patients harboring the XRCC3 Met241Met genotype versus 8.4 months for patients with Thr241Met and 3.1 months for those with Thr241Thr (P = .04). CPT-11/docetaxel plus cisplatin is active in patients with advanced esophagogastric cancer. XRCC3 Met241Thr polymorphisms could be a useful marker to predict prognosis in patients treated with a cisplatin-based chemotherapy. However, these results are required to be confirmed with a great number of patients.


Association Between Exposure to Heavy Metals and Systemic Sclerosis: the Levels of Al, Cd, Hg, and Pb in Blood and Urine of Patients.
Systemic sclerosis (SSc) is a multisystem connective tissue disease; exogenous factors-including heavy metals-may have a role in the disease pathogenesis. In this context, a study on the quantification of Al, Cd, Hg, and Pb in blood and urine of 27 SSc patients and 30 controls was carried out. Main findings were that Al was significantly depleted in blood and increased in urine of SSc patients respect to controls; and Pb was found slightly increased in blood and significantly decreased in SSc group. In addition, higher Hg levels in urine were found in SSc subjects with the higher severity of the disease. Females showed the most marked differences in the levels of blood Al, blood Pb, and urine Cd between patients and controls. Smoking, hobby, ingestion of contaminated food, job exposure may contribute to the bodily levels of Al, Hg, Pb in SSc patients. The results indicated that low, chronic, and multiple exposures to heavy metals-also through habits, diet, and environment-may influence the risk for SSc.


Proteolysis of Xenopus Cip-type CDK inhibitor, p16Xic2, is regulated by PCNA binding and CDK2 phosphorylation.
Cell division is positively regulated by cyclin-dependent kinases (CDKs) partnered with cyclins and negatively regulated by CDK inhibitors. In the frog, Xenopus laevis, three types of CDK inhibitors have been described: p27Xic1 (Xic1) which shares sequence homology with both p21Cip1 and p27Kip1 from mammals, p16Xic2 (Xic2) which shares sequence homology with p21Cip1, and p17Xic3 (Xic3) which shares sequence homology with p27Kip1. While past studies have demonstrated that during DNA polymerase switching, Xic1 is targeted for protein turnover dependent upon DNA, Proliferating Cell Nuclear Antigen (PCNA), and the ubiquitin ligase CRL4Cdt2, little is known about the processes that regulate Xic2 or Xic3. We used the Xenopus interphase egg extract as a model system to examine the regulation of Xic2 by proteolysis and phosphorylation. Our studies indicated that following primer synthesis during the initiation of DNA replication, Xic2 is targeted for DNA- and PCNA-dependent ubiquitin-mediated proteolysis and that Cdt2 can promote Xic2 turnover. Additionally, during interphase, Xic2 is phosphorylated by CDK2 at Ser-98 and Ser-131 in a DNA-independent manner, inhibiting Xic2 turnover. In the presence of double-stranded DNA ends, Xic2 is also phosphorylated at Ser-78 and Ser-81 by a caffeine-sensitive kinase, but this phosphorylation does not alter Xic2 turnover. Conversely, in the presence or absence of DNA, Xic3 was stable in the Xenopus interphase egg extract and did not exhibit a shift indicative of phosphorylation. During interphase, Xic2 is targeted for DNA- and PCNA-dependent proteolysis that is negatively regulated by CDK2 phosphorylation. During a response to DNA damage, Xic2 may be alternatively regulated by phosphorylation by a caffeine-sensitive kinase. Our studies suggest that the three types of Xenopus CDK inhibitors, Xic1, Xic2, and Xic3 appear to be uniquely regulated which may reflect their specialized roles during cell division or early development in the frog.


Investigation and evaluation of membrane fouling in a microbial fuel cell-membrane bioreactor systems (MFC-MBR).
Two membrane bioreactors with and without adding an electric circuit (named as MFC-MBR and C-MBR, respectively) were established to investigate the effects of micro-electric field on membrane fouling. With the aeration rate of 1.5 L/min, the synergistic effect of aeration and micro-electric field was the best in reducing membrane fouling and COD in treatment of a simulated phenol wastewater. Compared with C-MBR, the running time of MFC-MBR was extended for 16 days. Scanning electron microscope (SEM) and energy-dispersive X-ray detector (SEM-EDX) demonstrated that less foulants were attached to the membrane and the attachment was loosend in MFC-MBR. The decreased absolute value of zeta potential indicated repulsion among the negatively-charged sludge particles was reduced and flocculation of the sludge was improved, which alleviated the membrane fouling. The soluble microbial products (SMP) and loosely-bound extracellular polymeric substances (LB-EPS) were also decreased in MFC-MBR. It was found that migration and neutralization of the negatively-charged particles, and degradation of microorganisms contributed to the alleviation of membrane fouling. Moreover, the decreases of carbohydrates in LB-EPS led to higher protein/carbohydrates (PN/PS) ratio, which was a key parameter for alleviating membrane fouling. Meanwhile, the increase of tightly bound extracellular polymeric substances (TB-EPS) could also slow down membrane fouling. Because TB-EPS can be used as a binder to strengthen the flocculation of sludge particles.


Determination of prostaglandin E(2) by on-line solid-phase extraction-liquid chromatography with ultraviolet detection for microsomal prostaglandin E(2) synthase-1 inhibitor screening.
A rapid, robust and selective on-line solid-phase extraction-liquid chromatographic method with ultra-violet detection (on-line SPE-LC-UV) for microsomal prostaglandin E(2) synthase-1 (mPGES-1) inhibitor screening was developed and validated. Disrupted A549 cells were used as mPGES-1 source and the formation of prostaglandin E(2) (PGE(2)) out of the substrate prostaglandin H(2) (PGH(2)) was determined at 195 nm. Direct on-line sample clean up was achieved by automated column switch (C18 trap column) prior isocratic separation using a C18 analytical column. The on-line SPE-LC-UV method was accurate, precise and reproducible in the range of 71-1763 ng/ml for PGE(2) and met the generally accepted criteria for bioanalytical methods. The method was successfully applied to determine the IC(50) value of the known mPGES-1 inhibitor NS-398.


Performance of alginate films for retention of L-(+)-ascorbic acid.
In view of acting as controlled delivery systems for nutritional supplementation, therapy or antioxidant activity at interfaces, alginate films of different copolymer composition and glycerol plasticizer levels were developed in the presence of Ca(2+) for achieving higher stability of L-(+)-ascorbic acid (AA). The ability of the alginate network to preserve AA from hydrolysis, tested by storage under vacuum at 25 °C, only decreased with the relative humidity (RH) increase when alginates were mainly constituted by guluronic-guluronic acid blocks (GG), whereas also decreased with the glycerol level increase when mannuronic-mannuronic acid (MM) and/or alternating guluronic-mannuronic (GM+MG) flexible blocks were present in higher proportions. This result could be probably related to the lower capability of the latter alginate block compositions to immobilize water in the network as they are not able to constitute Ca(2+) mediated junction zones where water molecules are highly retained. Films also studied under air storage showed that even at less favorable conditions of RH and glycerol levels, both GG and GM+MG enriched alginate networks in general preserved AA from oxidation. It also demonstrated that hydrolysis is the principal way by which AA is lost when supported in films.


Improving Patient Safety: Implementing Dose Monitoring Software in Fluoroscopically Guided Interventions.
To assess whether dose monitoring software can be successfully implemented in fluoroscopically guided interventions and to provide dose data based on levels of complexity. After launching the software (DoseWatch; GE Healthcare Systems, Buc, France), data were collected for 6 months and analyzed by means of kerma-area product (KAP; Gy/cm(2)), cumulative air kerma (KA,R; Gy), and fluoroscopic time (minutes). Data analysis was executed by level of complexity as graded by the operators. Complexity grading was based on factors such as tortuosity and calcification of vessel, variant anatomy, and patient cooperation. The software successfully transferred dose data of 357 fluoroscopically guided procedures. KAP was 0.238-400 Gy/cm(2) with mean, median, and 75th percentile values of 46.0 Gy/cm(2), 163.2 Gy/cm(2), and 541.1 Gy/cm(2) (KA,R, 0.013-4.1 Gy; mean, median, 75th percentile, 0.48 Gy, 0.97 Gy, 3.98 Gy). Highest dose values were seen in transarterial chemoembolization (KAP mean, median, 75th percentile, 229.5 Gy/cm(2), 216.4 Gy/cm(2), 299.9 Gy/cm(2); KA,R mean, median, 75th percentile, 1.9 Gy, 1.2 Gy, 1.7 Gy). Analysis revealed that the level of complexity strongly correlated with KAP (r = 0.88; P < .001) whereas there was no direct correlation of KAP and fluoroscopy time. During the same intervention, KA,R and fluoroscopy time increased with level of complexity, but the correlation was not statistically significant. Implementation of dose monitoring software in fluoroscopically guided interventions can be successfully accomplished, and it facilitates data comparison.


NAM7 nuclear gene encodes a novel member of a family of helicases with a Zn-ligand motif and is involved in mitochondrial functions in Saccharomyces cerevisiae.
The yeast nuclear gene NAM7 was previously isolated within a genomic fragment of 7.7 kb (1 kb = 10(3) bases or base-pairs), having the ability to suppress mitochondrial intronic mutations defective in RNA splicing. We have identified and sequenced the region on the insert corresponding to the NAM7 gene. A long open reading frame has been revealed which could code for a protein of 971 amino acids. Comparison of the NAM7 putative protein with data libraries did not reveal any strong similarity with known proteins. However, the NAM7 protein contains several motifs typical for proteins interacting with nucleic acids: (1) five motifs diagnostic for a superfamily of helicases appear in the same order and with similar distances; (2) the N-terminal portion possesses potential Zn-ligand structures belonging to the C chi superfamily. Deletion of the chromosomal copy of NAM7 gene leads to a partial impairment in respiratory growth that is particularly striking at low temperature. Southern blot analysis of DNA extracted from a nam7 :: URA3 deleted strain revealed the presence of a second gene whose sequence is related to that of the NAM7 gene and which could participate in the same process.


Difficult memory task during postural tasks of various difficulties in young and older people: a pilot study.
This study examined the effects of a difficult and individually tailored additional cognitive task on postural stability and electromyographic (EMG) activities of the ankle dorsi- and plantar-flexors, in young and older individuals performing postural tasks of varying difficulties. Eight young (mean age=24 years) and eight older (74 years) men took part in the investigation. Centre of pressure velocity and surface EMG of ankle joint muscles were both examined during various postural conditions. The main findings suggested that high levels of muscle activity were a characteristic of age-related declines in postural stability. Moreover, during the complex posture, the postural instability, as well as the EMG activity of the ankle joint muscles, was decreased in older adults when the difficult memory task was added. Regarding young participants, the performance in the cognitive task was significantly improved during the complex posture compared to the easy one. These findings showed that the execution of a second task would make it possible to improve the performance in the original task. This pilot study seemed to show that, depending on age, the task of highest priority would be the cognitive one for young adults and the postural one for older people.


Occupational Attainment Among Parents in Germany and the US 2000-2016: The Role of Gender and Immigration Status.
In many OECD countries, women are underrepresented in high status, high paying occupations and overrepresented in lower status work. One reason for this inequity is the "motherhood penalty," where women with children face more roadblocks in hiring and promotions than women without children or men with children. This research focuses on divergent occupational outcomes between men and women with children and analyzes whether parental gender gaps in occupational status are more extreme for immigrant populations. Using data from the Luxembourg Cross-National Data Center, I compare changes in gendered occupational segregation from 2000 to 2016 in Germany and the USA among immigrant and native-born parents. Multinomial logistic regression models and predicted probabilities show that despite instituting policies intended to reduce parental gender inequality in the workforce, Germany fares worse than the USA in gendered occupational outcomes overall. While the gap between mothers' and fathers' probabilities of employment in high status jobs is shrinking over time in Germany, particularly for immigrant mothers, Germany's gender gaps in professional occupations are consistently larger than gaps in the US. Likewise, gender gaps in elementary/labor work participation are also larger in Germany, with immigrant mothers having a much higher likelihood of working in labor/elementary occupations than any other group-including US immigrant women. These findings suggest that work-family policies-at least those implemented in Germany-are not cure-all solutions for entrenched gender inequality. Results also demonstrate the importance of considering the interaction between gender and other demographic characteristics-like immigrant status-when determining the potential effectiveness of proposed work-family policies.


Determination of human plasma kininogen by a single radial immunodiffusion method and the bradykinin equivalent.
An SRI method is presented for the quantitation of native human plasma kininogen using a monospecific high avidity antiserum prepared against the conformational determinants of kininogen heavy chain (HC antigen). The SRI value of total human plasma kininogen averaged 0.260 +/- 0.052 g/l (+/- 2 SD) using a standard curve of normal human plasma in each assay (measuring range 0.016-0.260 g/l). The SRI data, confirmed by RIA, were compared with determination of the bradykinin equivalent by bioassay 4.30 +/- 0.052 mg/l (+/- 2 SD), generally accepted as a measure of total plasma kininogen. The SRI method does not discriminate between LMr and HMr kininogen but detects an increase of total kininogen independently of bradykinin release as a consequence of activated proteolysis. It is suggested that the SRI method can be applied to study levels of kininogen in clinical research.


Reduced receptor editing in lupus-prone MRL/lpr mice.
The initial B cell repertoire contains a considerable proportion of autoreactive specificities. The first major B cell tolerance checkpoint is at the stage of the immature B cell, where receptor editing is the primary mode of eliminating self-reactivity. The cells that emigrate from the bone marrow have a second tolerance checkpoint in the transitional compartment in the spleen. Although it is known that the second checkpoint is defective in lupus, it is not clear whether there is any breakdown in central B cell tolerance in the bone marrow. We demonstrate that receptor editing is less efficient in the lupus-prone strain MRL/lpr. In an in vitro system, when receptor-editing signals are given to bone marrow immature B cells by antiidiotype antibody or after in vivo exposure to membrane-bound self-antigen, MRL/lpr 3-83 transgenic immature B cells undergo less endogenous rearrangement and up-regulate recombination activating gene messenger RNA to a lesser extent than B10 transgenic cells. CD19, along with immunoglobulin M, is down-regulated in the bone marrow upon receptor editing, but the extent of down-regulation is fivefold less in MRL/lpr mice. Less efficient receptor editing could allow some autoreactive cells to escape from the bone marrow in lupus-prone mice, thus predisposing to autoimmunity.


Efficient structure-factor modeling for crystals with multiple components.
Diffraction intensities from a crystallographic experiment include contributions from the entire unit cell of the crystal: the macromolecule, the solvent around it and eventually other compounds. These contributions cannot typically be well described by an atomic model alone, i.e. using point scatterers. Indeed, entities such as disordered (bulk) solvent, semi-ordered solvent (e.g. lipid belts in membrane proteins, ligands, ion channels) and disordered polymer loops require other types of modeling than a collection of individual atoms. This results in the model structure factors containing multiple contributions. Most macromolecular applications assume two-component structure factors: one component arising from the atomic model and the second one describing the bulk solvent. A more accurate and detailed modeling of the disordered regions of the crystal will naturally require more than two components in the structure factors, which presents algorithmic and computational challenges. Here an efficient solution of this problem is proposed. All algorithms described in this work have been implemented in the computational crystallography toolbox (CCTBX) and are also available within Phenix software. These algorithms are rather general and do not use any assumptions about molecule type or size nor about those of its components.


Measurement of transmembrane peptide interactions in liposomes using Förster resonance energy transfer (FRET).
Present day understanding of the thermodynamic properties of integral membrane proteins (IMPs) lags behind that of water-soluble proteins due to difficulties in mimicking the physiological environment of the IMPs in order to obtain a reversible folded system. Despite such challenges faced in studying these systems, significant progress has been made in the study of the oligomerization of single span transmembrane helices. One of the primary methods available to characterize these systems is based on Förster resonance energy transfer (FRET). FRET is a widely used spectroscopic tool that provides proximity data that can be fitted to obtain the energetics of a system. Here we discuss various technical aspects related to the application of FRET to study transmembrane peptide oligomerization in liposomes. The analysis is based on FRET efficiency relative to the concentration of the peptides in the bilayer (peptide:lipid ratio). Some important parameters that will be discussed include labeling efficiency, sample homogeneity, and equilibration. Furthermore, data analysis has to be performed keeping in mind random colocalization of donors and acceptors in liposome vesicles.


Activation of T lymphocytes results in an increase in H-2-encoded neuraminidase.
The endogenous neuraminidase activity of various mouse lymphoid subpopulations and tissue compartments was examined by a sensitive fluorometric assay. These analyses indicated that activated T lymphocytes possessed a significantly higher level of intracellular neuraminidase than activated B or resting T or B lymphocytes. Examination of the level of neuraminidase in bone marrow, thymus, lymph node, and unfractionated spleen indicated that these lymphoid tissues contained significantly less neuraminidase than was detected in stimulated T cells. Kinetic studies revealed that the majority of the increase in neuraminidase activity occurred between 24 and 48 h following stimulation. Analysis of activated T lymphocytes prepared from a panel of inbred mouse strains indicated that cells from mice of the H-2v haplotype, which possess the Neu-1a allele and are deficient in liver neuraminidase, exhibited a level of activity which was significantly lower than that detected in stimulated T cells from other mouse strains. These results indicate that the endogenous neuraminidase activity of T lymphocytes increases upon stimulation, and that the level of this enzyme activity in lymphoid cells is also controlled by the Neu-1 locus, which is located in the H-2 region of the major histocompatibility complex.


A "wire-whip" catheter for selective catheterization of aortic branches.
A multipurpose "wire-ship" catheter has been developed for selective catheterization of branches arising from the aorta. The catheter tip is formed in three dimensions to allow simple selective catheterization and to provide improved stability during injection of contrast media by power injector or by hand. For successful catheterization it is essential to match the diameter of the catheter coil to the aortic lumen at the specific level to be studied; consequently, five standard sizes of coil diameter from 10--18 mm are currently produced. With an additional side hole in the coil, semiselective angiograms may be obtained. The wire-whip catheter has been used in over 200 angiographic examinations. The renal, celiac, superior and inferior mesenteric circulations have been most commonly studied, but other aortic branches such as the bronchial, intercostal, phrenic, and lumbar arteries have been catheterized as well. There have been no serious complications.


Evolving trends in combined modality therapy for pancreatic cancer.
Only 5%-15% of patients with pancreatic adenocarcinoma undergo potentially curative resection. Evidence that postoperative adjuvant therapy improves outcome is limited to a single randomized trial utilizing split-course chemoradiation. More aggressive regimens have developed and are associated with, at best, a modest improvement in patient outcome. The potentially significant morbidity associated with pancreaticoduodenectomy, which can compromise the delivery of postoperative chemoradiation, has led to the investigations of preoperative regimens. Although such an approach is feasible, its ultimate impact warrants further evaluation. Among the 4% of patients who present with unresectable or locally advanced disease, combined modality therapy has produced the most promising results. However, only modest improvements in survival have so far been achieved. Combined modality therapy with radioisotope implantation appears to have the greatest potential for improving local control and survival in these patients. Intraoperative radiation therapy (IORT) may be associated with lower morbidity than radioisotope implantation, but its impact may be limited by radiobiological disadvantage associated with single-dose boost therapy. The problem of distant metastasis remains significant. New chemotherapeutic agents have the potential to produce better results than those achieved with 5-fluorouracil. Continued advances in surgery, radiation, and systemic therapy should lead to the increased use of modern combined modality interventions with an associated further improvement in patient outcome.


The serotonin-2C agonist Lorcaserin delays intravenous choice and modifies the subjective and cardiovascular effects of cocaine: A randomized, controlled human laboratory study.
Lorcaserin is a modestly selective agonist for 2C serotonin receptors (5-HT2CR) approved for weight-loss therapy. This class can attenuate cue-induced responding and drug taking in preclinical studies, but effects in humans have not been reported. We evaluated effects of single 10 mg doses of lorcaserin on the subjective and reinforcing effects of cocaine, using a randomized, double-blind, within-subject, cross-over design. Male, non-treatment-seeking, regular cocaine users received either single doses of oral placebo (n = 9) or lorcaserin (n = 9), followed by low- or high- doses of intravenous cocaine (0.23 or 0.46 mg/kg-injection). They were then allowed to self-administer the lower dose of cocaine. Cocaine was well tolerated after lorcaserin pretreatment. Oral lorcaserin did not modify the number of cocaine injections self-administered. However, it prolonged the time over which participants made intravenous choices relative to the duration of monetary (cash) decisions. Lorcaserin increased ratings of 'high' and 'stimulated' after low-dose cocaine or vehicle, but decreased craving for cocaine after intravenous vehicle. It also caused small but significant increases in heart rate following noncontingent injections of intravenous placebo or cocaine. When active cocaine was self-administered, lorcaserin decreased heart rate after selection of a monetary choice, but increased it following an intravenous choice. Combined treatment with cocaine and lorcaserin was safe in a limited number of subjects, but did not diminish cocaine-motivated behavior or drug-induced 'high'. Some positive subjective effects of cocaine were enhanced by lorcaserin, and it delayed intravenous choices and decreased craving under some conditions. Effects on heart rate depended on the type of reinforcer being self-administered. clinicaltrials.gov Identifier, NCT02680288.


Spontaneous pneumomediastinum as an unusual complication of COVID-19 pneumonia.
Spontaneous pneumomediastinum is to consider in COVID-19 patients with progressive respiratory deterioration. It possibly reflects extensive alveolar injury and prompts close monitoring. Although generally self-limiting, it could be lifeߚthreatening.


Pyrazolopyridinones as functionally selective GABAA ligands.
2,5-Dihydro-3H-pyrazolo[4,3-c]pyridin-3-ones are GABAA receptor benzodiazepine binding site ligands, which can exhibit functional selectivity for the alpha3 subtype over the alpha1 subtype. SAR studies to optimize this functional selectivity are described.


The associations of body mass index with physical and mental aspects of health-related quality of life in Chinese patients with type 2 diabetes mellitus: results from a cross-sectional survey.
This study aimed to determine the associations of various clinical factors with generic health-related quality of life (HRQOL) scores among Hong Kong Chinese patients with type 2 diabetes mellitus (T2DM) in the outpatient primary care setting using the short-form 12 (SF-12). A cross-sectional survey of 488 Chinese adults with T2DM recruited from a primary care outpatient clinic was conducted from May to August 2008. Data on the standard Chinese (HK) SF-12 Health Survey and patients' socio-demographics were collected from face-to-face interviews. Glycaemic control, body mass index (BMI), chronic co-morbidities, diabetic complications and treatment modalities were determined for each patient through medical records. Associations of socio-demographic and clinical factors with physical component summary (PCS-12) and mental component summary scores (MCS-12) were evaluated using multiple linear regression. The socio-demographic correlates of PCS-12 and MCS-12 were age, gender and BMI. After adjustment for socio-demographic variables, the BMI was negatively associated with PCS-12 but positively associated with MCS-12. The presence of diabetic complications was associated with lower PCS-12 (regression coefficient:-3.0 points, p < 0.05) while being on insulin treatment was associated with lower MCS-12 (regression coefficient:-5.8 points, p < 0.05). In contrast, glycaemic control, duration of T2DM and treatment with oral hypoglycaemic drugs were not significantly associated with PCS-12 or MCS-12. Among T2DM subjects in the primary care setting, impairments in the physical aspect of HRQOL were evident in subjects who were obese or had diabetic complications whereas defects in the mental aspect of HRQOL were observed in patients with lower BMI or receiving insulin injections.


Foot-and-mouth disease virus degrades Rab27a to suppress the exosome-mediated antiviral immune response.
Foot-and-mouth disease (FMD) is a highly contagious infection caused by foot-and-mouth disease virus (FMDV). Exosomes are extracellular vesicles that mediate antiviral immune responses in host cells and could be used by pathogens to evade host cell immune responses. Whether FMDV affects exosome secretion or whether exosomes derived from FMDV-infected cells mediate host cell antiviral immune responses is not yet clarified. In this study, the exosomes were identified and extracted from FMDV-infected PK-15 cells, and it was found that FMDV inhibits exosome secretion. Further investigation revealed that FMDV suppresses exosomes by degrading Rab27a via the autophagy-lysosome pathway. Also, microRNA (miRNA) differential analysis was performed in exosomes, which revealed that miRNA-136 was highly differentially expressed in exosomes and may be the key miRNA that inhibits the proliferation of FMDV. In summary, these results showed that host cells take advantage of exosomes to mediate their antiviral immune response, while FMDV evades exosome-mediated immune responses by degrading the exosome molecular switch, Rab27a.


Prenatal diagnosis of Meckel-Gruber syndrome in a pregnancy obtained with ICSI.
The association of occipital encephalocele, cleft palate, postaxial polydactyly, polycystic kidneys, and hepatic cysts is well known as Meckel-Gruber syndrome (MGS). Nowadays, the diagnosis of MGS is usually performed prenatally by ultrasound findings. MGS was previously described following in vitro fertilization. We report a case of MGS diagnosed at 17 weeks in a pregnancy obtained with intra-cytoplasmic sperm injection (ICSI).


Voice problems due to virilization in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
Congenital adrenal hyperplasia (CAH) is an autosomal recessive inherited disorder in which the lack of 21-hydroxylase results in cortisol and aldosterone insufficiency and an overproduction of adrenal androgens. High levels of androgens in women may cause virilization of the larynx and a masculine voice. The purpose of the present study was to investigate subjective voice problems due to virilization in women with CAH. Participants were 42 women with CAH between 25 and 71 years of age, and 43 age-matched female healthy control subjects. All patients, but two, were in good disease control. A validated Swedish version of the Voice Handicap Index (VHI) and questions related to voice virilization were used. Endocrine data were obtained from medical files. Patients scored significantly higher on VHI when the results were divided into no/mild, moderate and severe voice handicap as compared with the control subjects. They rated significantly higher for 'dark voice' and for 'being perceived as a man on the phone' compared with controls. Seven per cent of the women with CAH had voice problems clearly related to voice virilization. High ratings of dark voice were significantly associated with long periods of under-treatment with glucocorticoids and higher bone mineral density but not with severity of mutation. Subjective voice problems due to voice virilization may occur in women with CAH. This further emphasizes the importance of avoiding long periods of increased androgen levels to prevent irreversible voice changes. For these patients, we recommend referral to voice assessment and treatment.


Improved 3D quantitative mapping of blood volume and endothelial permeability in brain tumors.
We describe a new method to allow simultaneous mapping of endothelial permeability and blood volume in intracranial lesions. The technique is based on a tumor leakage profile during the first pass (fp) of contrast bolus calculated from the time-dependent plasma-contrast concentration function (PCCF) in three-dimensional (3D) T1-weighted dynamic studies. The performance of the method has been evaluated by comparing results with those obtained from more conventional methods in patients with primary brain neoplasms. The new permeability maps (k(fp)) are visually compatible with those calculated using a conventional multicompartment model (k(tran)). Quantitatively, the new maps are free from overestimation of k(tran) due to first-pass effects. The new blood volume maps, which segment out the contamination of contrast leakage, agree closely with maps derived from susceptibility studies. The new method is fast, robust, and easy to perform. The method is suitable for use in clinical environments and is likely to be of benefit where longitudinal assessment of treatment response is required.


Some particular aspects of the microarchitecture of human coronary arteries.
The following light-microscopic features characterize the microarchitecture of human coronary arteries compared with other organ arteries of muscular type and similar size: (a) the rapid development of a diffuse thickened intima which in adolescents becomes the main layer of the coronary artery wall; (b) the slow post-natal increase in the number of circularly oriented rows of smooth muscle cells of the media; (c) the occurrence of numerous longitudinal muscle columns, particularly in arterial segments and branches which run from the base to the apex of the heart; (d) the complex organization of branching points, including the presence of large pads or cushions, a very thick intima and many longitudinal muscle columns, some of which exhibit a spiral course at the level of the branch mouths with the formation of muscle rings round the entrance orifices.


Immunohistochemical Characteristics of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma: A Systematic Review and Meta-Analysis.
Differentiating atypical fibroxanthoma (AFX) from pleomorphic dermal sarcoma (PDS) remains a challenge. Increasing the use of immunohistochemistry has led to the proposal of many immunomarkers that may aid in the diagnosis of AFX and PDS. In this meta-analysis, we investigate the immunohistochemical characteristics of AFX and PDS based on suggested immunomarkers in the literature. Second, we identify potential distinctive markers found in the tumors' respective immunohistochemical profiles. We included studies using immunomarkers on at least 10 consecutive patients with clinically and histopathologically verified AFX or PDS. The positive rates of the immunomarkers were pooled across the included studies with random-effects models. The immunomarkers were further categorized by a priori-chosen cutoffs in positive rates as positive markers (>90%) or negative markers (<10%). Differences between AFX and PDS were compared with Wald tests. We included 45 studies (1516 tumors) reporting on 35 immunomarkers. CD10 was positive in 94% (95% confidence interval, 87-99) of AFX cases and 100% (95% confidence interval, 99-100) of PDS cases. In accordance with the literature, both AFX and PDS were mainly negative for epithelial markers, melanocytic markers, markers of smooth muscle differentiation, and endothelial markers. None of the examined immunomarkers could distinguish AFX from PDS. Our results suggest that CD10 is a useful positive immunomarker for both AFX and PDS. We found no difference in immunohistochemical profile when comparing AFX with PDS. Our analysis suggests that CD10, AE1/AE3, CK5/CK6, p63, S100, SOX10, desmin, SMA, CD31, and ERG could be used to differentiate AFX and PDS from other spindle cell neoplasms.


Heterotopic pancreas in surgically resected stomach.
The heterotopic pancreas collected from the surgically resected stomachs were studied clinico-pathologically. The number of cases of heterotopic pancreas were 64; 43 in the stomach and 21 in the duodenal bulbus. They were corresponded to 1.2% in the 5446 resected stomachs. The operated cases with this lesion were frequently found in the age of thirty to fifty with male predominance. Thirty eight cases of them were combined with other gastro-duodenal diseases, especially gastric or duodenal ulcers. About 90% of these lesions were found in the pylorus and antrum. They were situated frequently in the greater curvature, posterior and anterior wall, and rarely in the lesser curvature. Their size was ranged about 0.3 to 4.7 cm in diameter, and about 80% of them within 3 cm in diameter. Macroscopically, 49 polypoid, 8 nipple-like, 7 flat and 1 thickening folded lesions were found, respectively. The bridging folds were found in 9 cases, 13.8%. Microscopically, 30, 29 and 6 lesions of type I, II, and III types according to Heinrich's classification were found, respectively. The ulcer formation of the mucosal surface of the heterotopic pancreas was found at rate of 10%, and cystic transformation in about 6%.


Positive inotropic and negative chronotropic effect of pantethine on isolated cardiac muscle of guinea-pigs.
It was demonstrated that pantethine, a component of co-enzyme A, produces positive inotropic and negative chronotropic actions in isolated cardiac muscle preparations from guinea-pigs.


Contaminated and uncontaminated feeding influence perceived intimacy in mixed-sex dyads.
It was expected that viewers watching adult mixed-sex pairs dining together will give higher ratings of the perceived intimacy and involvement of the pair if feeding is displayed while eating, especially if the feeding involves contaminated (i.e., with potential germ transfer) foods. Our hypotheses were tested using a design in which participants viewed five videotapes in varying order. Each video showed different mixed-sex pairs of actors sharing meal and included a distinct form of food sharing or none. These were shown to 50 small groups of young adults in quasi-random sequences to control for order effects. Immediately after each video, viewers were asked about the attractiveness, attraction and intimacy in the dyad they had just observed. As predicted, videos featuring contaminated feeding consistently produced higher ratings on involvement and attraction than those showing uncontaminated feeding which, in turn, mostly produced higher ratings on involvement and attraction than those showing no feeding behaviors.


Conservative management of fish bone-induced large bowel perforation: Case report.
Fish bone ingestion is one of the common medical complaint. Most foreign bodies passed safely through gastrointestinal tract (GIT) without any complications. The clinical presentation of foreign body ingestion is similar to other conditions such as diverticulitis. Most literatures focus on the surgical management of complications secondary to fish bone ingestion. In this case we report a case of an elder patient with complain of progressive abdominal pain. 71-year-old female, admitted to surgical ward with the complain of progressive abdominal pain. Physical examination revealed right upper quadrant tenderness with normal digital rectal examination. An abdominal X-ray was obtained and was not remarkable. Computed tomography (CT) chest, abdomen, and pelvis with contrast revealed proximal transverse colon wall thickening with reginal soft tissue thickening, inflammation and a radiopaque foreign body. Patient was managed conservatively by bowel rest, and antibiotics. Fish bone swallowing account for two third of these foreign bodies. Most of the foreign bodies pass through the gastrointestinal tract (GIT)without any significant harm or complications. The clinical presentation of perforation secondary to fish bone is nonspecific which may delay the diagnosis. The management can be either medical or surgical depend on many factors. Although, foreign body ingestion is one of the common complaints in the medical practice, its complications is extremely uncommon. However, improvement of medical imaging increased sensitivity and specify in detecting fish bone.


Two New Quinazoline Derivatives from the Moss Endophytic Fungus Aspergillus sp. and Their Anti-inflammatory Activity.
Two new quinazoline derivatives versicomides E (1) and F (2), and 10 known compounds (3-12) were isolated from the moss endophytic fungus Aspergillus sp. Their structures were determined on the basis of extensive spectroscopic data analysis and ECD calculations. Among them, the compound 7 (6-hydroxy-3-methoxyviridicatin) was first reported as a natural product. Inhibition on LPS-induced NO production in RAW 264.7 murine macrophages found that compounds 5, 7 and 8 showed significant inhibitory effects on NO production, with IC50 values of 49.85, 22.14 and 46.02 μM respectively.


Increased N-acetylaspartate in model mouse of Pelizaeus-Merzbacher disease.
To evaluate the N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) biochemical pathways in the brain of myelin synthesis-deficient (msd) mouse, a model of Pelizaeus-Merzbacher disease (PMD). We performed magnetic resonance imaging and proton magnetic resonance spectroscopy (¹H-MRS) of the thalamus for msd and wildtype mice with a 7.0 T magnet. NAA and NAAG were independently measured by high-performance liquid chromatography (HPLC). Immunohistochemical analysis using anti-Mbp, Gfap, Ng2, and NeuN antibodies were also performed. ¹H-MRS in msd mice revealed increased total NAA (tNAA, NAAþNAAG), creatine, glutamine, and glutamate and decreased choline (Cho). HPLC analysis revealed increases of both NAA and NAAG in the msd brains. Histologically, the msd brains revealed hypomyelination and astrogliosis. Oligodendrocyte progenitor cells and neurons were normal in number in the thalamus wherein ¹H-MRS was obtained. The evidence suggests that the neurochemical derangement in the msd mice may be a primary increase of NAA resulting in a secondary increase of NAAG. Increased tNAA with decreased Cho detectable on ¹H-MRS may be an important marker for PMD, and might be used to distinguish it from more common neurological disorders that have decreased tNAA.


Evaluating the Impact of a School-Based Youth-Led Health Education Program for Adolescent Females in Mumbai, India.
India's 120 million adolescent girls often have limited opportunities to receive health education, as health-related content in school curricula can be minimal, and the few existing external interventions for this demographic rarely cover multiple topics. This study conducted a program evaluation of Girls Health Champions, a school-based peer education intervention in Mumbai, India that educates girls about leading causes of adolescent morbidity and mortality, including nutrition, mental health, and sexual & reproductive health. Female participants ages 12 to 16 in the eighth, ninth, and tenth standards were recruited at five participating schools in Mumbai, India to learn a multi-topic health curriculum from their peers, with a subset of ninth standard participants in each school trained as the peer educators. Using a quasi-experimental design, participant survey data was collected three times during the 2016-2017 academic year: at baseline, immediately following the peer-led education sessions, and five months following these sessions. Outcomes of interest included change in knowledge levels and health attitudes following the intervention, as well as retention at mid-year. An additional outcome was the change in self-reported leadership skills of peer educators before and after participating. Compared to baseline, participants demonstrated statistically significant increases in knowledge levels (+48%, p < 0.001) and positive shifts in health-related attitudes (+42%, p < 0.001). These changes were maintained at mid-year (+29% for knowledge levels, p < 0.001; +37% for attitudes, p < 0.001). Findings were consistent when data was stratified by standard and peer educator status (peer educators versus non-peer educators). Peer educators also demonstrated a statistically significant increase in their interest in health promotion. This study demonstrates the effectiveness of the peer education delivery model and finds school-based, peer-led programs covering a range of adolescent health topics can significantly increase knowledge and shift attitudes of program participants. Such benefits can accrue to both peer educators and non-peer educator program participants.


Structural change of soft tissue anterior cruciate ligament reconstructions with cross-pin fixation between immediate and postoperative 8 weeks: a study with use of magnetic resonance imaging.
There is some controversy regarding the optional method for proximal fixation in anterior cruciate ligament reconstruction surgery using soft tissue grafts. Concern about the strength of fixation has limited rehabilitation during the early postoperative period. Graft slippage occurs after cross-pin femoral fixation during the early healing period when the strength of the tendon-to-bone interface is lowest. Case series; Level of evidence, 4. Coronal and sagittal T2-weighted magnetic resonance images of arthroscopically reconstructed anterior cruciate ligaments performed in 18 consecutive knees were evaluated. The images were taken along the tunnel direction an average of 4 days (after the hemovac removal) and 8 weeks (recovery >120 degrees range of motion) after surgery. The distance was measured from the uppermost point of the graft to the upper border of the superior cross pin. To reduce the intra- and interobserver bias, the measurements were taken twice by 2 orthopaedic surgeons for all patients. Interrater and intrarater reliability were determined twice by 2 orthopaedic surgeons. The intrarater (0.88 and 0.93) and interrater (0.79 and 0.81) agreement ranged from 0.79 to 0.93. One of the 18 patients showed complete breakage of the 2 cross pins 8 weeks after surgery, even though the pins were intact 4 days postoperatively. From an analysis of the remaining 17 patients, there was no significant difference in the coronal and sagittal measurements taken at postoperative 4 days and 8 weeks (P = .170-.737) and all individual cases showed less than 3 mm slippage. The expansion mechanism of the cross pin works well during the early healing period. However, further studies on the long-term outcomes are required. In addition, further study on the strength of this fixation technique is needed because 1 of the 18 patients showed broken pins.


iPSCs derived from insulin resistant offspring of type 2 diabetic patients show increased oxidative stress and lactate secretion.
The genetic factors associated with insulin resistance (IR) are not well understood. Clinical studies on first-degree relatives of type 2 diabetic (T2D) patients, which have the highest genetic predisposition to T2D, have given insights into the role of IR in T2D pathogenesis. Induced pluripotent stem cells (iPSCs) are excellent tools for disease modeling as they can retain the genetic imprint of the disease. Therefore, in this study, we aimed to investigate the genetic perturbations associated with insulin resistance (IR) in the offspring of T2D parents using patient-specific iPSCs. We generated iPSCs from IR individuals (IR-iPSCs) that were offspring of T2D parents as well as from insulin-sensitive (IS-iPSCs) individuals. We then performed transcriptomics to identify key dysregulated gene networks in the IR-iPSCs in comparison to IS-iPSCs and functionally validated them. Transcriptomics on IR-iPSCs revealed dysregulated gene networks and biological processes indicating that they carry the genetic defects associated with IR that may lead to T2D. The IR-iPSCs had increased lactate secretion and a higher phosphorylation of AKT upon stimulation with insulin. IR-iPSCs have increased cellular oxidative stress indicated by a high production of reactive oxygen species and higher susceptibility to H2O2 -induced apoptosis. IR-iPSCs generated from offspring of diabetic patients confirm that oxidative stress and increased lactate secretion, associated with IR, are inherited in this population, and may place them at a high risk of T2D. Overall, our IR-iPSC model can be employed for T2D modeling and drug screening studies that target genetic perturbations associated with IR in individuals with a high risk for T2D.


Biological evaluation of 3-[(18)F]fluoro-α-methyl-D-tyrosine (D-[(18)F]FAMT) as a novel amino acid tracer for positron emission tomography.
3-[(18)F]Fluoro-α-methyl-L-tyrosine (L-[(18)F]FAMT) is a useful amino acid tracer for positron emission tomography (PET) imaging of malignant tumors. Because D-amino acids are not well distributed in non-target organs and are rapidly excreted in urine, the D-isomer of [(18)F]FAMT could allow clear PET imaging of tumors early after administration. In this study, we prepared 3-[(18)F]fluoro-α-methyl-D-tyrosine (D-[(18)F]FAMT) and evaluated its usefulness. D-[(18)F]FAMT was synthesized according to the method for preparation of L-[(18)F]FAMT. The in vitro and in vivo stability of [(18)F]FAMT were evaluated by high-performance liquid chromatography. Cellular uptake of [(18)F]FAMT was evaluated using LS180 colon adenocarcinoma cells. Biodistribution studies were performed in LS180 tumor-bearing mice, and the tumors were imaged using a small-animal PET scanner. The radiolabeling yield of D-[(18)F]FAMT was approximately 10 %, similar to that of L-[(18)F]FAMT. Over 95 % of D-[(18)F]FAMT remained intact in mice until 60 min after administration. D-[(18)F]FAMT was gradually taken up by the LS180 cells. Tumor uptake of D-[(18)F]FAMT was competitively inhibited by pretreatment with α-methyl-L-tyrosine, a selective substrate for the system L-amino acid transporter 1 (LAT1), suggesting the involvement of LAT1 in tumor uptake of D-[(18)F]FAMT. In biodistribution studies, D-[(18)F]FAMT showed rapid clearance from the blood, marked accumulation and retention in the tumor, and lower accumulation in non-target organs, especially kidney and pancreas, compared to L-[(18)F]FAMT. The amount of D-[(18)F]FAMT in the tumor was also reduced, and tumor-to-blood ratio and tumor-to-muscle ratio of D-[(18)F]FAMT were similar to those of L-[(18)F]FAMT at every time point. PET imaging with D-[(18)F]FAMT did not provide a clear image of the tumor early after administration. However, D-[(18)F]FAMT provided higher tumor-to-background contrast than L-[(18)F]FAMT. D-[(18)F]FAMT showed rapid blood clearance, low accumulation in non-target organs, and tumor-selective imaging compared with L-[(18)F]FAMT. Thus, D-[(18)F]FAMT could potentially serve as a novel PET tracer for imaging malignant tumors.


Preparation of biological material for X-ray microanalysis of diffusible elements. II. Comparison of different methods of drying ultrathin cryosections cut without a trough liquid.
The appearance of ultrathin, dry-cut cryosections of brown adipose tissue and liver was found to be strongly dependent upon adequate freeze-drying. If freeze-drying was inadequate, diffusion of substances could be demonstrated and freezing damage was not apparent. Diffusion was manifested as an electron dense film over structural features such as triglyceride droplet profiles and the edges of the section; when this film was thick, X-ray signals for P, S, Cl, K and Ca could be detected from it, in different proportions to those found in the section. The frequency and intensity of diffusion were lowered by decreasing the temperature in the cryochamber from about 200 K +/- 5 K to 163 K +/- 5 K by forced evaporation of liquid N2 using an extra heater. The lowest incidence of diffusion was obtained in conjunction with this device, by leaving the sections in the cryochamber for at least 2 h during drying, either over a drying agent or under moderate vacuum. Such sections showed a narrow zone (A) at the edge that lacked obvious ice-crystal damage, a thicker zone (B) of moderate ice-crystal damage and the bulk of the interior (zone C) severely damaged by freezing. Qualitatively different, reproducible X-ray spectra could be obtained from ultrastructural features even in areas showing some signs of diffusion.


Molecular epidemiology of COVID-19 in Oman: A molecular and surveillance study for the early transmission of COVID-19 in the country.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been proven to be lethal to human health, which affects almost every corner of the world. The objectives of this study were to add context to the global data and international genomic consortiums, and to give insight into the efficiency of the contact tracing system in Oman. We combined epidemiological data and whole-genome sequence data from 94 samples of SARS-CoV-2 in Oman to understand the origins, genetic variation, and transmissibility. The whole-genome size of sequence data was obtained through a customized SARS-COV-2 research panel. Amplifier methods ranged from 26 Kbp to 30 Kbp and were submitted to GISAID. The study found that P323L (94.7%) is the most common mutation, followed by D614G (92.6%) Spike protein mutation. A unique mutation, I280V, was first reported in Oman and was associated with a rare lineage, B.1.113 (10.6%). In addition, the study revealed a good agreement between genetic and epidemiological data. Oman's robust surveillance system was very efficient in guiding the outbreak investigation processes in the country, the study illustrates the future importance of molecular epidemiology in leading the national response to outbreaks and pandemics.


Dynamic contrast-enhanced MRI radiomics nomogram for predicting axillary lymph node metastasis in breast cancer.
The goal of this study is to develop and validate a radiomics nomogram integrating the radiomics features from DCE-MRI and clinical factors for the preoperative diagnosis of axillary lymph node (ALN) metastasis in breast cancer patients. A total of 432 patients with breast cancer were enrolled in this retrospective study and divided into a training cohort (n = 296) and a validation cohort (n = 136). Radiomics features were extracted from the second phase of dynamic contrast enhanced (DCE) MRI images. The least absolute shrinkage and selection operator (LASSO) regression method was used to screen optimal features and construct a radiomics signature in the training cohort. Multivariable logistic regression analysis was used to establish a radiomics nomogram model based on the radiomics signature and clinical factors. The predictive performance of the nomogram was quantified with respect to discrimination and calibration, which was further evaluated in the independent validation cohort. Fourteen ALN metastasis-related features were selected to construct the radiomics signature, with an area under the curve (AUC) of 0.847 and 0.805 in the training and validation cohorts, respectively. The nomogram was established by incorporating the histological grade, multifocality, MRI report lymph node status and radiomics signature and showed good calibration and excellent performance for ALN detection (AUC of 0.907 and 0.874 in the training and validation cohorts, respectively). The decision curve, which demonstrated the radiomics nomogram, displayed promising clinical utility. The radiomics nomogram can be used as a noninvasive and reliable tool to assist clinicians in accurately predicting ALN metastasis in breast cancer preoperatively.


Effectiveness and Safety of Regdanvimab in Patients With Mild-To-Moderate COVID-19: A Retrospective Cohort Study.
Regdanvimab has decreased the time to clinical recovery from coronavirus disease 2019 (COVID-19) and lowered the rate of oxygen therapy according to the results from phase 2/3 randomized controlled trial. More information is needed about the effects and safety of regdanvimab. We analyzed data for patients with high-risk mild or moderate COVID-19 being admitted to Busan Medical Center between December 1, 2020 and April 16, 2021. A propensity score (PS) matched analysis was conducted to compare patients treated with and without regdanvimab. The primary outcome was in-hospital death or disease aggravation which means the need for oxygen therapy (low- or high-flow oxygen therapy and mechanical ventilation) and secondary outcomes comprised the length of hospital stay and adverse reactions. Among 1,617 selected patients, 970 (60.0%) were indicated for regdanvimab. Of these, 377 (38.9%) were administered with regdanvimab. Among a 1:1 PS-matched cohort of 377 patients each treated with and without regdanvimab, 19 (5%) and 81 (21.5%) reached the composite outcome of death, or disease aggravation, respectively (absolute risk difference, -16.4%; 95% confidence interval [CI], -21.1, -11.7; relative risk difference, 76.5%; P < 0.001). Regdanvimab significantly reduced the composite outcome of death, or disease aggravation in univariate (odds ratio [OR], 0.194; 95% CI, 0.112-0.320; P < 0.001) and multivariable-adjusted analyses (OR, 0.169; 95% CI, 0.095-0.289; P < 0.001). The hospital stay was shorter for the group with than without regdanvimab. Some hematological adverse reactions were more frequent in the group without regdanvimab, but other adverse reactions did not significantly differ between the groups. Regdanvimab was associated with a significantly lower risk of disease aggravation without increasing adverse reactions.


Determining the IgG concentrations in bovine colostrum and calf sera with a novel enzymatic assay.
Immune protection in newborn calves relies on a combination of the timing, volume and quality of colostrum consumed by the calf after birth. Poor quality colostrum with inadequate immunoglobulin concentration contributes to failed transfer of passive immunity in calves, leading to higher calf morbidity and mortality. Therefore, estimating colostrum quality and ensuring the transfer of passive immunity on farm is of critical importance. Currently, there are no on-farm tools that directly measure immunoglobulin content in colostrum or serum. The aim of this study was to apply a novel molecular assay, split trehalase immunoglobulin G assay (STIGA), to directly estimate immunoglobulin content in dairy and beef colostrum and calf sera, and to examine its potential to be developed as on-farm test. The STIGA is based on a split version of trehalase TreA, an enzyme that converts trehalose into glucose, enabling the use of a common glucometer for signal detection. In a first study, 60 dairy and 64 beef colostrum and 83 dairy and 84 beef calf sera samples were tested with STIGA, and the resulting glucose production was measured and compared with radial immunodiffusion, the standard method for measuring immunoglobulin concentrations. Pearson correlation coefficients between the methods were determined and the sensitivity, specificity, and accuracy of the test were calculated for different colostrum quality and failed transfer of passive immunity cut-off points. The correlations of the STIGA measured by colorimetric enzymatic reaction compared to radial immunodiffusion for dairy and beef colostrum were 0.72 and 0.73, respectively, whereas the correlations for dairy and beef sera were 0.9 and 0.85, respectively. Next, STIGA was tested in a blinded study with fresh colostrum and serum samples where the correlation coefficient was 0.93 and 0.94, respectively. Furthermore, the performance of STIGA followed by glucometer readings resulted in correlations with radial immunodiffusion of 0.7 and 0.85 for dairy and beef colostrum and 0.94 and 0.83 for dairy and beef calf serum. A split TreA assay was validated for measurement of the immunoglobulin content of colostrum and calf sera using both a lab-based format and in a more user-friendly format compatible with on-farm testing.


Improving the Stratification of Patients With Intermediate-risk Prostate Cancer.
Intermediate-risk prostate cancer (IR PCa) phenotypes may vary from favorable to unfavorable. National Comprehensive Cancer Network (NCCN) criteria help distinguish between those groups. We studied and attempted to improve this stratification. A total of 4048 (NCCN favorable: 2015 [49.8%] vs. unfavorable 2033 [50.2%]) patients with IR PCa treated with radical prostatectomy were abstracted from an institutional database (2000-2018). Multivariable logistic regression models predicting upstaging and/or upgrading (Gleason Grade Group [GGG] IV-V and/or ≥ pT3 or pN1) in IR PCa were developed, validated, and directly compared with the NCCN IR PCa stratification. All 4048 patients were randomly divided between development (n = 2024; 50.0%) and validation cohorts (n = 2024; 50.0%). The development cohort was used to fit basic (age, prostate-specific antigen, clinical T stage, biopsy GGG, and percentage of positive cores [all P < .001]) and extended models (age, prostate-specific antigen, clinical T stage, biopsy GGG, prostate volume, and percentage of tumor within all biopsy cores [all P < .001]). In the validation cohort, the basic and the extended models were, respectively, 71.4% and 74.7% accurate in predicting upstaging and/or upgrading versus 66.8% for the NCCN IR PCa stratification. Both models outperformed NCCN IR PCa stratification in calibration and decision curve analyses (DCA). Use of NCCN IR PCa stratification would have misclassified 20.1% of patients with ≥ pT3 or pN1 and/or GGG IV to V versus 18.3% and 16.4% who were misclassified using the basic or the extended model, respectively. Both newly developed and validated models better discriminate upstaging and/or upgrading risk than the NCCN IR PCa stratification.


Optimized sliding surface predictive control of a voltage source inverter with improved steady-state performance.
In this paper, an optimized sliding surface predictive control of a three-phase voltage source inverter is introduced. In power electronics, the model predictive control method (MPC) is broadly used and applied to a wide range of energy conversion systems. However, analyzing the stability of the MPC is not a straightforward task, and Lyapunov-based approaches are used to examine the stability characteristics in most cases. MPC is a nonlinear control technique, and the traditional frequency-domain stability tools cannot be used to examine the closed-loop stability. Therefore, a poor design of the MPC without considering the stability may worsen the system performance. Even the norm choice of the objective function leads to closed-loop instability, for example, ℓ1 norm is not a sufficient choice to guarantee the global asymptotical stability. Even though ℓ1 norm offers a low computational burden during the online optimization process, the system may suffer from closed-loop instability. For all these reasons, a stability-guaranteed objective function design procedure is proposed in this paper. The proposed objective function selection process is based on the sliding-mode control theory. The objective function is reformulated as a sliding surface function, and the switching combination that satisfies the sliding mode control stability criteria is selected as an optimum input. The mathematical concepts are experimentally validated, and the results demonstrate the potency of the proposed strategy.


Prolonged cognitive-motor impairments in children and adolescents with a history of concussion.
We investigated whether children and adolescents with concussion history show cognitive-motor integration (CMI) deficits. Asymptomatic children and adolescents with concussion history (n = 50; mean 12.84 years) and no history (n = 49; mean: 11.63 years) slid a cursor to targets using their finger on a dual-touch-screen laptop; target location and motor action were not aligned in the CMI task. Children and adolescents with concussion history showed prolonged CMI deficits, in that their performance did not match that of no history controls until nearly 2 years postevent. These CMI deficits may be due to disruptions in fronto-parietal networks, contributing to an increased vulnerability to further injury. Current return-to-play assessments that do not test CMI may not fully capture functional abilities postconcussion.


Effects of dorsal root section on spinocervical tract neurones in the cat.
1. In nine cats, dorsal roots L(6) and L(7) were sectioned under pentobarbitone anaesthesia using strict aseptic precautions. In two cats all lumbosacral roots except L(6) were sectioned under similar conditions. 27-75 days after the dorsal rhizotomies, under chloralose anaesthesia, neurones of the spinocervical tract (s.c.t.) were recorded electrophysiologically both extracellularly and intracellularly, their response properties and receptive fields were analysed, and they were injected with horseradish peroxidase (HRP). Twenty-five cells were recorded extracellularly and twenty were recorded intracellularly and stained with the enzyme.2. Of the twenty neurones stained with HRP, one was located in caudal L(5), eleven in L(6) and eight in L(7). Five cells had no receptive field, either before or after current injection, two cells had no field before injection but after current injection responded to either electrical stimulation of peripheral nerve or to brusque tapping on the limb; six neurones responded only to tapping before current injection and two of these showed a more clearly defined receptive field after current injection; six neurones had a receptive field and responded with impulses to hair movement and/or pressure within a well-defined area but this area was surrounded by skin from which excitatory post-synaptic potentials could be elicited; only one neurone had an apparently normal receptive field.3. Of the twenty-five neurones recorded extracellularly, eleven had no receptive field, four responded only to tapping on the limb, three had receptive fields consisting of an area of low threshold plus an area responding to brusque or noxious mechanical stimulation, and seven neurones had apparently normal receptive fields.4. Neurones with no observable receptive fields were either silent with no resting activity, or had very low rates of background activity consisting of isolated single impulses or short bursts of impulses. No neurones in de-afferented segments had high rates of background activity.5. There were no alterations in the normal somatotopy of the dorsal horn. All fifteen s.c.t. neurones injected with HRP and which had a localizable receptive field had fields appropriately located in the somatotopic map. There were no electro-physiological signs of inappropriate connexions.6. The dendritic trees of fifteen neurones injected with HRP were reconstructed. With the exception of one cell which appeared grossly disorganized (but which was the one cell with an apparently normal receptive field), there were no obvious differences between the dendritic trees of de-afferented cells and normal cells from the same and other cats. Their dendritic trees had similar rostro-caudal, medio-lateral and dorso-ventral extents to normal cells, and appeared to exhibit similar degrees of branching. There was a suggestion that de-afferented neurones had rather more of their dorsally-directed distal dendrites invading lamina II than normal cells, but the sample size was too small to make this more than a possibility.7. It is concluded that after dorsal rhizotomy, s.c.t. neurones lose part or all of their afferent input and that within 75 days do not show any signs of new or inappropriate connexions.


Differential response of linear and angular psoralens in PUVA-induced apoptosis in HL-60 cells.
Treatment of cells with UVA radiation in combination with linear psoralens induces a cell-cycle block and subsequent apoptosis, whereas angular derivatives produce apoptosis without affecting the cellular cycle.


The reliability of surrogate information about oral contraceptive use, smoking, height and weight collected from men about their wives.
Ninety-nine female hospital patients and their husbands were asked to complete separate questionnaires about the woman's history of using oral contraceptives as well as her height, weight and cigarette smoking habits. The questionnaires were completed in the presence of a research nurse to ensure that there was no discussion. Reports of height, weight and smoking status showed a good agreement between the women and their husbands. Husbands usually reported accurately on whether the woman was a current or past user of oral contraceptives, but most of them were unable to name the brand of oral contraceptive that was used, or give an estimate of the duration of use.


Laparoscopic Greater Curvature Plication for the Treatment of Obesity: a Systematic Review.
During the last decade, laparoscopic greater curvature plication (LGCP) has been used as a bariatric procedure for the treatment of obesity, regarded as less invasive and less expensive than other surgical bariatric procedures. We aimed to systematically review the literature and highlight recent clinical data regarding outcomes of LGCP in the treatment of obesity. A comprehensive research of Pubmed database on LGCP was performed. The search was conducted on the first of May 2020 and was not limited to any date range. Outcomes of interest were surgical technique, postoperative complications, weight loss outcomes, comorbidities improvement or resolution, and revisional surgeries after technical failure or weight regain. Fifty-three articles were eligible for inclusion, with 3103 patients undergoing LGCP (mean age: 13.8-55 years). Mean preoperative body mass index (BMI) ranged from 31.2 to 47.8 kg/m2. Mean operative time ranged from 48 to 193 min. Length of hospital stay ranged from 0.75 to 7.2 days. Most studies provided postoperative follow-up up to 12 months. Mean percentage of excess weight loss (%EWL) ranged from 30.2 to 71.1% and 35 to 77.1% at 6 and 12 months post-LGCP, respectively. Only one study followed patients for more than 10 years and mean %EWL at 1, 5, and 10 years was 67%, 55%, and 42%, respectively. LGCP seems to be an acceptable surgical procedure for the treatment of obesity, especially in centers having a low medical budget. However, most existing comparative studies report superiority of LSG regarding weight loss.


Gasdermin Pore Forming Activities that Promote Inflammation from Living and Dead Cells.
Gasdermins are proteins that can self-assemble into membrane channels (also known as pores). These pores can serve as conduits for the secretion of cytosolic molecules, with the most commonly studied being members of the interleukin-1 family of cytokines. However, gasdermin pore forming activities must be tightly regulated, as the channels that they form can lead to a lytic form of cell death known as pyroptosis. Recent studies have revealed multiple mechanisms that control gasdermin activities within cells and identified gasdermin proteins in organisms as diverse as bacteria, humans and yeast. In this Review, we discuss the molecular and cellular mechanisms that regulate gasdermin pore formation. These mechanisms of gasdermin regulation likely explain the flexibility of these proteins to display cell type specific (and potentially organism specific) functions.


Regulation of N-glycosylation. Long term effect of cyclic AMP mediates enhanced synthesis of the dolichol pyrophosphate core oligosaccharide.
The influence of 8-bromo-cAMP on N-glycosylation in JEG-3 choriocarcinoma cells was investigated using the octanoyl-tripeptide (OTP; N-octanoyl-asparagyl-125I-tyrosyl-threonine amide) as glycosyl acceptor. In cells pretreated with 8-bromo-cAMP (2.5 nM to 1 mM), the amount of glycosylated OTP released into the culture medium was increased up to 35-fold. Under the same conditions, a 23-fold higher quantity of the glycoprotein hormone human chorionic gonadotropin was secreted. Preincubation of 10-90 min with 250 microM 8-bromo-cAMP caused only a 2-fold increase of the total amount of glycosylated OTP, whereas it was approximately 20-fold higher when the pretreatment was extended to 40 h. This strongly suggests involvement of gene activation rather than cAMP-mediated phosphorylation. The specific activity of the oligosaccharyltransferase, as well as the mRNA levels of ribophorin I and II (presumptive subunits of the enzyme), remained unchanged. In pulse-chase experiments, [3H]mannose incorporation into dolichol-linked Glc3Man9(GlcNAc)2 was up to 20-fold higher in cells pretreated with 8-bromo-cAMP (250 microM, 40 h). The radioactivity was chased from the lipid-linked oligosaccharide pool and shifted to the glycoprotein fraction 10 times more rapidly in the pretreated cells. The flux of [3H]mannose through the dolichol phosphate mannose pool was only slightly affected by the 8-bromo-cAMP pretreatment. Our investigations show that the oligosaccharyltransferase activity in JEG-3 cells is not rate-limiting. N-Glycosylation seems to be controlled by the amount of lipid-linked core oligosaccharide. The size of the lipid-linked core oligosaccharide pool, as well as the flux through, is markedly increased by pretreatment with 8-bromo-cAMP.


Protein/Polysaccharide Composite toward Multi-in-One Toxin Removal in Blood with Self-Anticoagulation and Biocompatibility.
Biocompatible adsorbents play an essential role in hemoperfusion. Nevertheless, there are no hemoperfusion adsorbents that can simultaneously remove small and medium toxins, including bilirubin, urea, phosphor, heavy metals, and antibiotics. This bottleneck significantly impedes the miniaturization and portability of hemoperfusion materials and devices. Herein, a biocompatible protein-polysaccharide complex is reported that exhibits "multi-in-one" removal efficacy for liver and kidney metabolism wastes, toxic metal ions, and antibiotics. Through electrostatic interactions and polysaccharide-mediated coacervation, adsorbents can be prepared by simply mixing lysozyme (LZ) and sodium alginate (SA) together in seconds. The LZ/SA absorbent presented high adsorption capacities for bilirubin, urea, and Hg2+ of up to 468, 331, and 497 mg g-1 , respectively, and the excellent anti-protein adsorption endowed LZ/SA with a record-high adsorption capacity for bilirubin in the interference of serum albumin to simulate the physiological environment. The LZ/SA adsorbent also has effective adsorption capacity for heavy metals (Pb2+ , Cu2+ , Cr3+ , and Cd2+ ) and multiple antibiotics (terramycin, tetracycline, enrofloxacin, norfloxacin, roxithromycin, erythromycin, sulfapyrimidine, and sulfamethoxazole). Various adsorption functional groups exposed on the adsorbent surface significantly contribute to the excellent adsorption capacity. This fully bio-derived protein/alginate-based hemoperfusion adsorbent has great application prospects in the treatment of blood-related diseases.


Guidance of neural regeneration on the biomimetic nanostructured matrix.
Biomimetic materials are used for creating microsystems to control cell growth spatially and elicit specific cellular responses by combining complex biomolecules with nanostructured surfaces. Intercellular cell-to-cell and cell-to-extracellular matrix (ECM) interactions in biomimetic materials have demonstrated potential in the development of drug discovery platforms and regeneration medicine. In this study, we developed a biomimetic nanostructured matrix by using various ECM molecular layers to create a biomimetic and biocompatible environment for realizing neuronal guidance in neural regeneration medicine. Silicon-based substrates possessing nanostructures were modified using different ECM proteins and peptides to develop a biomimetic and biocompatible environment for studying neural behaviors in adhesion, proliferation, and differentiation. The substrates were flat glass, flat silicon wafers (FWs), and nanorod-structured wafers prepared using wet etching. The three substrates were then functionalized using laminin-1 peptide, PA22-2-contained active isoleucine-lysine-valine-alanine-valine (IKVAV) peptide, and poly-d-lysine (PDL), separately. When PC12 cells were cultured and differentiated on the modified substrates, the cells were able to elongate the neurites on the glass and FW, which was coated with three types of peptide. More differentiated neurons were observed on the nanorod-structured wafers coated with laminin than on those coated with IKVAV or PDL. For achieving directional guidance of neurite outgrowth, substrates exhibiting a grating pattern of nanorods were partially collapsed by the pulling force of water, leaving few nanorods, which support the net form of laminin on the surface. Furthermore, we fabricated the topological nanostructure-patterned wafer coated with laminin and successfully manipulated the extension and direction of neurites by using more than 80 μm of a single soma. This approach demonstrates potential as a facile and efficient method for guiding the direction of single axons and for enhancing neurite outgrowth in studies on nerve regenerative medicine.


Cadmium and lead adsorption by a natural polysaccharide in MF membrane reactor: experimental analysis and modelling.
In the present work, Pb(2+) and Cd(2+) adsorption onto a natural polysaccharide has been studied in membrane reactors. The process involves a stirred semi-batch reactor for the adsorption step and a microfiltration (MF) process in order to confine the particles. Due to their lower affinity for the biosorbent, Cd(2+) ions were found to breakthrough the process faster than Pb(2+) cations. The experimental results showed the technical feasibility of the pilot. A mass balance model based on the Langmuir equilibrium isotherm was used to describe the adsorption process. This relation is able to predict experimental data under different operating conditions: the adsorbent and metal concentrations, and the permeate flow rate. Based on these results, it is demonstrated that the biosorbent studied represents an interesting low-cost solution for the treatment of metal ions polluted waters.