Incomplete reporting of enhanced recovery elements and its impact on achieving quality improvement.
Enhanced recovery (ER) protocols are used widely in surgical practice. As protocols are multidisciplinary with multiple components, it is difficult to compare and contrast reports. The present study examined compliance and transferability to clinical practice among ER publications related to colorectal surgery. PubMed, Embase and Cochrane Central Register databases were searched for current colorectal ER manuscripts. Each publication was assessed for the number of ER elements, whether the element was explained sufficiently so that it could be transferred to clinical practice, and compliance with the ER element. Some 50 publications met the reporting criteria for inclusion. A total of 22 ER elements were described. The median number of elements included in each publication was 9, and the median number of included patients was 130. The elements most commonly included in ER pathways were early postoperative diet advancement (49, 98 per cent) and early mobilization (47, 94 per cent). Early diet advancement was sufficiently explained in 43 (86 per cent) of the 50 publications, but only 22 (45 per cent) of 49 listing the variable reported compliance. The explanation for early mobilization was satisfactory in 41 (82 per cent) of the 50 publications, although only 14 (30 per cent) of 47 listing the variable reported compliance. Other ER elements had similar rates of explanation and compliance. The most frequently analysed outcome measures were morbidity (49, 98 per cent), length of stay (47, 94 per cent) and mortality (45, 90 per cent). The current standard of reporting is frequently incomplete. To transfer knowledge and facilitate implementation of pathways that demonstrate improvements in perioperative care and recovery, a consistent structured reporting platform is needed.


Increased resistance of the Chinese hamster mutant irs1 cells to monofunctional alkylating agents by transfection of the E. coli or mammalian N3-methyladenine-DNA-glycosylase genes.
Irs1 cells are mutants of the Chinese hamster cell line V79-4, and exhibit cross-sensitivity to various DNA-damaging agents, especially to the alkylating compounds methyl methanesulfonate and ethyl methanesulfonate. To test whether this sensitivity was due to the persistence of alkylated residues in DNA, we have transfected irs1 cells with the pMSG expression vector containing two coding sequences for enzymes of different origin, either the E. coli AlkA gene, coding for 3-methyladenine-DNA-glycosylase II, or rat APDG cDNA, encoding alkylpurine-DNA-glycosylase. The two coding sequences for the repair enzymes were ligated in the pMSG vector, under the control of the MMTV-LTR promoter, which is responsive to glucocorticoid regulation. The presence of the AlkA gene or of the APDG cDNA in the transfected cells was detected by Southern blot analysis and the transcription of these foreign sequences was checked by Northern hybridization of the cellular RNA. The transfected irs1 cells treated with [3H]dimethylsulfate removed the 3-methyladenine residues more efficiently from their DNA than the control cells. Irs1 cells harboring the AlkA or the APDG gene become about 2- and 3-fold more resistant to the toxic effect of methyl methanesulfonate, respectively. However, a 3-fold resistance to ethyl methanesulfonate was only observed in irs1 cells harboring the mammalian APDG cDNA.


Estimation of body weight in Indian elephants (Elephas maximus indicus).
Thirty-nine adult Indian elephants (Elephas maximus indicus) of both sexes and various ages and weights, belonging to the Forest Department of the Government of Kerala (India), Temple Devaswoms, Gemini Circus and other private agencies, were used to derive formulae to predict body weight and height from body measurements. Several models were fitted separately for males and females and also for adults irrespective of sex. The best prediction of body weight (W) in kg was obtained for adults irrespective of sex by using two parameters, the body length (L) in cm from the base of the forehead to the base of the tail, and the chest girth (G) in the formula W = -1010 + 0.036 (L x G). No single parameter gave as accurate a prediction of the body weight, and the inclusion of height as a third parameter did not improve the prediction. No significant improvement in the accuracy of prediction resulted from the use of different formulae for males and females. An equation to predict the height at the shoulders (H) in cm from the right forefoot circumference (C) in cm in adult elephants irrespective of sex was also derived. This was H = -1.60 + 1.99 C.


An essential role for PTIP in mediating Hox gene regulation along PcG and trxG pathways.
During Drosophila development, Polycomb-group and Trithorax group proteins function to ensure correct maintenance of transcription patterns by epigenetically repressing or activating target gene expression. To get a deep insight into the PcG and trxG pathways, we investigated a BRCT domain-containing protein called PTIP, which was generally identified as a transcriptional coactivator and belongs to the TRR complex. At the genome scale, we sorted given PTIP-binding peaks into two groups: PTIP/TRR-cobound and PTIP/PC-cobound peaks. In particular, we found that PTIP mediates the molecular switch between H3K4me3/H3K27ac and H3K27me3 histone modifications at TRR or PC occupied regions. Thus, we suggest that PTIP is a mediator rather than a dedicated co-activator along PcG and trxG pathways. Our hypothesis is further supported by the genetic assay: PTIP interacts genetically with either PcG or TrxG in a dosage-dependent manner, suggesting that PTIP functions as a co-factor of PcG/TrxG proteins. In addition, in accordance with the analysis of ChIP-seq, these genetic interactions correlate with modified ectopic HOX protein levels in imaginal discs, which reveals an essential role for PTIP in PcG-mediated Hox gene repression. Hence, we reveal a novel role for PTIP in the epigenetic regulation of gene expression along PcG and trxG pathways.


Quantitative computed tomography and computed tomography in children.
Quantitative computed tomography (QCT) methodologies have been instrumental in deepening our understanding of bone acquisition and strength during childhood. Important publications in the last year have drawn attention to the functional muscle-bone unit, showing that factors such as population ancestry, bone size, and muscle composition are additional dimensions of bone strength that affect muscle-bone relationships. The role of adiposity in pediatric bone health is complex and may vary by sex, puberty stage, and degree of obesity. Several new studies have demonstrated the association of peripheral QCT (pQCT) outcomes with fracture, although pQCT outcomes are not superior to dual-energy x-ray absorptiometry measures in this regard. New high-resolution pQCT studies document transient weakness in mid-puberty that coincides developmentally with the period of peak fracture incidence. These new studies will ultimately help us understand the development of sex differences in bone strength that emerge in adolescence.


Gemcitabine, cisplatin, and dexamethasone (GDP) in combination with methotrexate and pegaspargase is active in newly diagnosed peripheral T cell lymphoma patients: a phase 2, single-center, open-label study in China.
Peripheral T cell lymphomas (PTCL) are less responsive to anthracycline-containing regimen such as CHOP and carry a poor prognosis. In this prospective study, we investigated gemcitabine, cisplatin, and dexamethasone (GDP) combined with methotrexate (MTX) and pegaspargase (PEG-L) as front-line treatment in PTCL. Eligible newly diagnosed PTCL patients received 4 cycles of the GDP-ML chemotherapy every 28 days. After 4 cycles, responding patients continued to receive either autologous stem cell transplantation or the MTX/cytarabine (MA) regimen for consolidation. This trial is registered with www.chictr.org.cn (ChiCTR-ONC-12002055). A total of 65 patients were enrolled with a median follow-up of 38.5 months. The overall response rate (ORR) was 55.4%, and complete remission rate (CR) was 33.8%. The median overall survival (OS) was 16 months, and the 1-year and 2-year OS were 59.1% and 38.2%, respectively. The median PFS was only 8 months. The main adverse event was hematologic toxicity: 50% patients showed grade III/IV neutropenia. GDP-ML for the first-line treatment of PTCL patients is an effective induction regimen compared with standard CHOP, and the toxicity was more significant but acceptable. However, future studies exploring new drug combinations are warranted to overcome relapse after remission. ClinicalTrials.gov Identifier: NCT02987244.


Local recurrence of breast cancer caused by core needle biopsy: Case report and review of the literature.
Needle tract seeding is the implantation of tumor cells at the site of needle passage during needle biopsy. Histopathological examination of resected specimens after biopsy shows an incidence of 22%-50%. However, reports of actual local recurrence are extremely rare. Here we report such a case. A 67-year-old woman was diagnosed with ductal carcinoma by histopathology and underwent right mastectomy and sentinel lymph node biopsy. Histopathological examination revealed non-invasive ductal carcinoma. One year after the first operation, a mass was found at the site of the core needle biopsy (CNB) scar near the previous surgical wound on the right chest. Histological examination revealed the tumor as adenocarcinoma, and a skin lesion resection was performed. After surgery, radiation therapy and endocrine therapy were performed. She remains relapse-free as of this writing, 9 months after resection. Reports of local recurrence due to needle tract seeding are extremely rare. We found nine cases of mastectomy and seven cases of partial resection performed for the first surgery; six patients received radiation therapy and 10 did not. Histological diagnosis at the time of the first operation was invasive carcinoma in all cases. The risk of seeding is high with multiple punctures in CNB, in cases with a short period until surgery, and in mucinous carcinoma. Considering these factors, CNB puncture should preferably be at a site that is included in the resection area during surgery. If not resected, close follow-up is necessary considering the possibility of local recurrence.


Factors influencing streambed hydraulic conductivity and their implications on stream-aquifer interaction: a conceptual review.
The estimation and modeling of streambed hydraulic conductivity (K) is an emerging interest due to its connection to water quality, aquatic habitat, and groundwater recharge. Existing research has found ways to sample and measure K at specific sites and with laboratory tests. The challenge undertaken was to review progress, relevance, complexity in understanding and modeling via statistical and geostatistical approaches, literature gaps, and suggestions toward future needs. This article provides an overview of factors and processes influencing streambed hydraulic conductivity (K) and its role in the stream-aquifer interaction. During our synthesis, we discuss the influence of geological, hydrological, biological, and anthropogenic factors that lead to variability of streambed substrates. Literature examples document findings to specific sites that help to portray the role of streambed K and other interrelated factors in the modeling of hyporheic and groundwater flow systems. However, studies utilizing an integrated, comprehensive database are limited, restricting the ability of broader application and understanding. Examples of in situ and laboratory methods of estimating hydraulic conductivity suggest challenges in acquiring representative samples and comparing results, considering the anisotropy and heterogeneity of fluvial bed materials and geohydrological conditions. Arriving at realistic statistical and spatial inference based on field and lab data collected is challenging, considering the possible sediment sources, processes, and complexity. Recognizing that the K for a given particle size group includes several to many orders of magnitude, modeling of streambed K and groundwater interaction remain conceptual and experimental. Advanced geostatistical techniques offer a wide range of univariate or multi-variate interpolation procedures such as kriging and variogram analysis that can be applied to these complex systems. Research available from various studies has been instrumental in developing sampling options, recognizing the significance of fluvial dynamics, the potential for filtration, transfer, and storage of high-quality groundwater, and importance to aquatic habitat and refuge during extreme conditions. Efforts in the characterization of natural and anthropogenic conditions, substrate materials, sediment loading, colmation, and other details highlight the great complexity and perhaps need for a database to compile relevant data. The effects on streambed hydraulic conductivity due to anthropogenic disturbances (in-stream gravel mining, contaminant release, benthic activity, etc.) are the areas that still need focus. An interdisciplinary (hydro-geo-biological) approach may be necessary to characterize the magnitude and variability of streambed K and fluxes at local, regional scales.


Chloroquine induced haemolysis and acute renal failure in subjects with G-6-PD deficiency.
Three male children with G-6-PD deficiency developed intravascular haemolysis leading to acute renal insufficiency following the administration of chloroquine. In two cases chloroquine seemed to be the only offending agent. One child required peritoneal dialysis. All patients showed complete recovery. The prevalence of this deficiency in India is discussed.


Stealth microplastics pollutants: Toxicological evaluation of polyethylene terephthalate-based glitters on the microalga Desmodesmus sp. and its color effect.
Polyethylene terephthalate-based glitters (PET glitters) are a potential source of primary microplastics in the environment. However, the bioeffects of PET glitters and the associated leachates remain largely unknown. In this study, we investigated the individual and combined toxicity of five colors (silver, black, red, green, and blue) of PET glitters and their corresponding leachates on the cellular responses of Desmodesmus sp. The results indicated that the photosynthesis of Desmodesmus sp. could be partly affected by PET glitters through the shading effect, but not that of growth. Conversely, the leachates of red and green PET glitters significantly inhibited the growth of the microalga, suggesting a higher risk associated with additives leached from these colors of PET glitters. Furthermore, the adverse effects of the co-occurrence of PET glitters and leachates were closely related to oxidative stress responses in the microalgal cells, along with a color effect, which could be mainly attributed to variations in the composition and abundance of toxic additives in different colors of PET glitters. Overall, our findings provide insights into the ecological risks posed by glitters in aquatic environments and emphasize the importance of considering color factors in assessing microplastics toxicity.


Orbitofrontal sulcogyral morphology in patients with cocaine use disorder.
Orbitofrontal cortex (OFC) is thought to be involved in appropriate processing of rewarding stimuli, and abnormal OFC structure and function has been found in patients with substance use disorders. Atypical patterns of the H-sulcus in the OFC have been primarily identified with schizophrenia, but also with bipolar disorder, both of which are associated with comorbid substance use. Given the high rates of substance use within Axis I psychiatric disorders, it is reasonable to consider how frequencies of OFC patterns in populations with only substance use compare to controls. This information is crucial to disentangle whether atypical frequencies of H-sulcus sulcogyral patterns within psychopathology are associated with the psychiatric or substance use phenotype. Here, we present the first analysis of H-sulcus sulcogyral patterns in a population of adult black men with (n = 84) and without (n = 24) cocaine use disorder (CUD). We find that OFC sulcogyral patterns are not significantly different from the control group, indicating that OFC sulcogyral patterns are not disrupted in patients with CUD. As exploratory analyses, we describe OFC sulcogyral pattern subtypes in this cohort as well as an additional control group (n = 52), in order to add to the growing body of literature on OFC sulcogyral pattern characterization.


Circumstances and factors of sleep-related sudden infancy deaths in Japan.
Sudden unexpected death in infancy (SUDI) comprises both natural and unnatural causes of death. However, few epidemiological surveys have investigated SUDI in Japan. This retrospective study was conducted to investigate the latest trends of circumstances and risk factors of SUDI cases in which collapse occurred during sleep. Forensic pathology sections from eight universities participated in the selection of subjects from 2013 to 2018. Data obtained from the checklist form were analyzed based on information at postmortem. There were 259 SUDI cases consisting of 145 male infants and 114 female infants with a mean birth weight of 2888 ± 553 and 2750 ± 370 g, respectively. Deaths most frequently occurred among infants at 1 month of age (18%). According to population data as the control, the odds ratio (95% confidence interval) of mother's age ≤19 years was 11.1 (6.9-17.7) compared with ages 30-39. The odds ratio for the fourth- and later born infants was 5.2 (3.4-7.9) compared with the frequency of first-born infants. The most frequent time of day for discovery was between 7 and 8 o'clock, and the time difference from the last seen alive was a mean of 4.1 h. Co-sleeping was recorded for 61%, and the prone position was found for 40% of cases at discovery. Mother's smoking habit exhibited an odds ratio of 4.5 (2.9-5.8). This study confirmed the trends that have been observed for sudden infant death syndrome; particularly, very high odds ratios were evident for teenage mothers and later birth order in comparison with those in other developed countries. Neglect was suspected in some cases of the prolonged time to discovery of unreactive infants. To our knowledge, this is the first report of an extensive survey of SUDI during sleep in Japan.


An individualized regional citrate anticoagulation protocol for hemodialysis: a real-world retrospective study.
To evaluate the safety and effectiveness of an individualized regional citrate anticoagulation (RCA) protocol for hemodialysis. In this single-center, retrospective study, blood coagulation in the extracorporeal circulation, adverse reactions, in vivo ionized calcium (iCa2+) concentrations, and the infusion dose of citrate during RCA in hemodialysis were observed in 98 patients from February 2021 to March 2022. A total of 98 patients underwent RCA during hemodialysis 362 times, and blood coagulation occurred in the extracorporeal circulation 29 times. Among the 29 cases of coagulation, most of the patients exhibited hypercoagulability, and among approximately 80% of the treatments, the deviation between the actual infusion rate of citrate in the extracorporeal circulation and the theoretical value was ± 10%. After hemodialysis, pH values and bicarbonate ion (HCO3-) levels were clearly improved, and online conductivity monitoring (OCM) values and blood coagulation scores in the extracorporeal circulation were identical to those measured in similar studies. An individualized RCA protocol for hemodialysis is safe, effective, simple, and inexpensive and can meet the needs of individualized treatment; therefore, its application is worthy of promotion.


Validation of the 24,25-dihydroxyvitamin D3 to 25-hydroxyvitamin D3 ratio as a biomarker of 25-hydroxyvitamin D3 clearance.
The formation of 24,25-dihydroxyvitamin D (24,25(OH)2D) from 25-hydroxyvitamin D (25(OH)D) is the primary mechanism for the metabolic clearance of 25(OH)D, and is regulated by tissue-level vitamin D activity. The ratio of 24,25(OH)2D3 to 25(OH)D3 in blood (vitamin D metabolite ratio, VDMR) is postulated to be a marker of 25(OH)D3 clearance, however this has never been tested. We measured baseline 24,25(OH)2D3 and 25(OH)D3 concentrations in 87 participants by liquid chromatography-tandem mass spectrometry. Following an infusion of deuterated 25(OH)D3, blood samples for each participant were collected over 56 days and analyzed for deuterated vitamin D metabolites. 25(OH)D3 clearance and the deuterated metabolite-to-parent AUC ratio (ratio of the AUC of deuterated 24,25(OH)2D3 to that of deuterated 25(OH)D3) were calculated. We compared the VDMR with these two measures using correlation coefficients and linear regression. Participants had a mean age of 64 ± 11years, 41 % were female, 30 % were self-described Black, 28 % had non-dialysis chronic kidney disease (CKD) and 23 % had kidney failure treated with hemodialysis. The VDMR was strongly correlated with 25(OH)D3 clearance and the deuterated metabolite-to-parent AUC ratio (r = 0.51 and 0.76, respectively). Adjusting for 25(OH)D3 clearance or the deuterated metabolite-to-parent AUC ratio in addition to clinical covariates, lower VDMR was observed in participants with CKD and kidney failure than in healthy controls; in Black than White participants; and in those with lower serum albumin. Our findings validate the VDMR as a measure of 25(OH)D3 clearance. This relationship was biased by characteristics including race and kidney disease, which warrant consideration in studies assessing the VDMR.


Possible mechanisms of neutrophil activation in Behçet's disease.
Behçet's disease (BD) is a systemic inflammatory disorder characterized by recurrent episodes of acute inflammation consisting mainly of neutrophil infiltration around blood vessels in affected tissues. BD probably occurs due to neutrophil-based innate immune responses orchestrated by a complex interplay among gamma-delta T lymphocytes, natural killer T cells, monocytes and Th17 lymphocytes in which type-I interferon is possibly a key element for inflammatory downregulation. However, strong evidence is still scarce. This article compiles the literature in an attempt to summarize the possible mechanisms by which neutrophils are activated in BD and suggests directions for future research.


Significant enhancement of the sensing characteristics of In2O3 nanowires by functionalization with Pt nanoparticles.
We report a significant enhancement in the gas sensing properties of In(2)O(3) nanowires by functionalizing their surfaces with Pt nanoparticles. For Pt-functionalization, In(2)O(3)-Pt core-shell nanowires are synthesized by the sputtering deposition of Pt layers on bare In(2)O(3) nanowires. Next, continuous Pt shell layers are transformed into Pt nanoparticles of cubic phase by heat treatment. In an O(2) gas sensing test, the Pt-functionalized In(2)O(3) nanowires reveal exceptionally higher sensitivity and faster response than bare In(2)O(3) nanowires.


Neural mechanism of selective finger movement independent of synergistic movement.
Muscle synergy is important for simplifying functional movement, which constitutes spatiotemporal patterns of activity across muscles. To execute selective finger movements that are independent of synergistic movement patterns, we hypothesized that inhibitory neural activity is necessary to suppress enslaved finger movement caused by synergist muscles. To test this hypothesis, we focused on a pair of synergist muscles used in the hand opening movement, namely the index finger abductor and little finger abductor (abductor digiti minimi; ADM), and examined whether inhibitory neural activity in ADM occurs during selective index finger abduction/adduction movements and/or its imagery using transcranial magnetic stimulation and F-wave analysis. During the index finger adduction movement, background EMG activity, F-wave persistence, and motor evoked potential (MEP) amplitude in ADM were elevated. However, during the index finger abduction movement, ADM MEP amplitude remained unchanged despite increased background EMG activity and F-wave persistence. These results suggest that increased spinal excitability in ADM is counterbalanced by cortical-mediated inhibition only during selective index finger abduction movement. This assumption was further supported by the results of motor imagery experiments. Although F-wave persistence in ADM increased only during motor imagery of index finger abduction, ADM MEP amplitude during motor imagery of index finger abduction was significantly lower than that during adduction. Overall, our findings indicate that cortical-mediated inhibition contributes to the execution of selective finger movements that are independent of synergistic hand movement patterns.


Mitochondrial Transplantation: A Critical Analysis.
"Mitochondrial transplantation" refers to a procedure for introducing isolated mitochondria into a damaged area of a heart or other organ. A considerable amount of data has been accumulated on the therapeutic effects of "mitochondrial transplantation" in animals with ischemic heart damage. In 2017, the first attempts were made to apply this procedure in a clinic. The authors of the method suggest that exogenous mitochondria penetrate into cardiomyocytes, retaining functional activity, and compensate for impaired energy output of endogenous mitochondria. This hypothesis contradicts the well-known fact of loss of mitochondrial functions in the presence of high concentrations of Ca2+, which are characteristic of the extracellular medium. This review critically considers the possible mechanisms of the therapeutic effect of "mitochondrial transplantation".


Optimized ultra performance liquid chromatography tandem high resolution mass spectrometry method for the quantification of paraquat in plasma and urine.
A simple, sensitive and specific ultra performance liquid chromatography coupled to electrospray tandem high resolution mass spectrometry (UPLC-ESI-HRMS/MS) method has been developed and validated for quantification of paraquat in plasma and urine. The sample preparation was carried out by one-step protein precipitation with acetonitrile. The paraquat was separated with a HILIC column in 10min. Detection was performed using Q Exactive Orbitrap mass spectrometer by Targeted-MS/MS scan mode. Methodological parameters, such as ammonium formate concentration, formic acid concentration, spray voltage, capillary temperature, heater temperature and normalized collision energy were optimized to achieve the highest sensitivity. The calibration curve was linear over the concentration range of LOQ-1000ng/mL. LOD was 0.1 and 0.3ng/mL, LOQ was 0.3 and 0.8ng/mL for urine and plasma, respectively. The intra- and inter-day precisions were <7.97% and 4.78% for plasma and urine. The accuracies were within the range 93.51-100.90%. The plasma and urine matrices had negligible relative matrix effect in this study. This method was successfully applied to determine paraquat concentration in plasma samples with hemoperfusion from 5 suspected paraquat poisoning patients.


Risk-Adjusted Assessment of the Learning Curve for Pure Laparoscopic Donor Hepatectomy for Adult Recipients.
Studies on pure laparoscopic donor hepatectomy (PLDH) have been reported. However, only few studies have reported on the learning curve of PLDH. In this report, we aimed to determine the learning curve of PLDH in adult patients using cumulative sum (CUSUM) and risk-adjusted CUSUM (RA-CUSUM) analyses. The data of donors who underwent PLDH at a single center between December 2012 and May 2022 were retrospectively reviewed. The learning curve was evaluated using the CUSUM and RA-CUSUM methods based on surgery duration. Forty-eight patients were finally included in the present study. The mean operation time was 393.6 ± 80.3 min. PLDH was converted to laparotomy in three cases (6.3%). According to the Clavien-Dindo classification, nine cases (18.8%) had higher-than-grade III postoperative complications and the most frequent complications were biliary complications. The CUSUM graph shows two peaks, at the 13th and 27th case. The multivariate analysis revealed that a body mass index ≥ 23 kg/m2 and intraoperative cholangiography were the only factors that were independently associated with longer operation time. Based on these results, an RA-CUSUM analysis was performed to assess the learning curve, which showed a decrease in the learning curve after 33 to 34 PLDH procedures. A learning curve effect was demonstrated in this study after 33 to 34 PLDH procedures. There are relatively many biliary complications, and it is necessary to further examine the method of bile duct transection.


Indicators for choosing an optimal mix of major working postures.
North American workers usually stand while working, and prolonged standing is associated with discomfort and cardiovascular problems. Since prolonged sitting is also associated with health problems, and standing postures differ as to mobility and access to seating, it is desirable to identify an optimal mix of postures. As a step towards this identification, it is desirable to develop indicators of potential health effects that respond to changes in work requirements. We observed 65 subjects who usually stood at work, in four types of workplaces. Pressure-pain threshold (PPT) recorded on the plantar surface was used as an indicator of discomfort and arterial blood pressure was used as an indicator of cardiovascular effects. PPT after work was significantly lower than that before work. Sitting for even a small part of the day appeared to be protective. The effects of static vs. dynamic work on PPT and arterial blood pressure may differ.


Neurological consequences of magnesium deficiency: correlations with epilepsy.
1. The plasma calcium and magnesium concentrations of sheep have been manipulated by feeding liquid diets with various calcium and magnesium concentrations. 2. When the magnesium status of the diet was low, both plasma calcium and magnesium concentrations declined, but the decline in calcium was much more rapid and extensive when the content of calcium in the diet was also low. This loss of calcium control in magnesium deficiency was attributed to end-organ resistance to parathyroid hormone. 3. Correlation between plasma and CSF calcium and magnesium concentrations indicated that convulsions occurred when CSF magnesium and plasma calcium concentrations declined. 4. The neurological mechanisms likely to be responsible for the induction of these convulsions are discussed and the factors precipitating convulsions in magnesium deficiency and epilepsy are compared.


Plasma netrin-1 levels significantly increase in smokers.
Netrin-1 is a laminin like protein that has recently been suggested to involve in the pathophysiology of atherosclerosis and treatment targets. The relationship between netrin-1 and atherosclerosis has not been evaluated in a human research previously and the effect of smoking on plasma netrin-1 levels as well. In this study, we aimed to evaluate plasma netrin-1 levels in smokers and non-smokers and the impact of smoking on netrin-1 levels. Our second aim was to evaluate the existence of peripheral artery disease in these groups by means of ankle brachial index (ABI) measurements and the relation between plasma netrin-1 levels and peripheral artery disease. Smoker and non-smoker male patients were contributed in the study, 112 males in each group. ABI of all patients was determined with an automatic device and plasma netrin-1 levels were quantified with an enzyme-linked immunosorbent assay. Netrin-1 levels were compared between smoker and non-smoker cases, and the cases with and without peripheral arterial disease. Plasma netrin-1 levels of smokers (4.54±2.87pg/mL) were significantly higher than in non-smokers (3.81±1.26pg/mL) (p=0.015). Similarly, netrin-1 levels of cases with peripheral arterial disease (6.21±2.16pg/mL) were significantly higher than the ones without peripheral arterial disease (4.07±2.16pg/mL) (p=0.002). Amount of smoking (packet⋅year) and ABI were found to be significantly related with netrin-1 levels. The relationship between PAD and netrin-1 levels remained significant after adjusting for smoking status. We can conclude that plasma netrin-1 levels significantly increase in smokers and peripheral artery disease is significantly related with netrin-1 levels after adjusting for smoking status.


Secular trends of birthweight in boys from 1950 to 2010.
Birthweight is an indicator of fetal development and intrauterine conditions and is associated with future health outcomes. Secular birthweight trends prior to the 1970s are mostly unknown. Our aim was to explore secular birthweight trends in Swedish boys from 1950 to 2010. We have collected detailed growth data including birthweight from archived School Health Care records for children born in Gothenburg from 1946 and onwards and established a unique population-based cohort, the Body Mass Index Epidemiology Study (BEST). The birthweight cohort spans six decades (1950-2010) and includes 46,548 boys. The mean birthweight of the complete study cohort was 3580 ± 562 g. Linear regression analysis of the entire period revealed a minimal negative secular trend for birthweight (BETA = -0.4 g/year; p < 0.01). However, three distinct trends appeared during sub-periods: a decrease 1950-80, an increase 1980-2000 and another decrease 2000-2010. We demonstrate that birthweight in boys has undergone periodic decreases and subsequent increases, but the overall trend from the 1950s to the present is stable.


Pancreatic adenomas in infants and children: current surgical management.
Islet cell adenomas are an important consideration in infants and children with hypoglycemia due to hyperinsulinism. Between 1965 and 1977, 32 patients with hyperinsulinism were seen at the Children's Hospital of Philadelphia. Sixteen of these patients underwent surgery. Eight patients had single pancreatic adenomas, 5 of whom were infants under 1 yr of age. In 3 infants an adenoma was recognized and removed at the time of surgery. In 4 patients a subtotal pancreatectomy was successful in removing the adenoma. One infant is whom the adenoma was not included in the subtotal pancreatectomy died postoperatively with intractable hypoglycemia. Of the 7 patients cured by surgery, 6 are normal and 1 has brain damage due to delay in treatment of hypoglycemia. One child has mild diabetes. A combined medical and surgical protocol has been developed that permits rapid diagnosis of hyperinsulinism and selection of candidates for surgery. Infants under 1 yr of age who fail to respond to diazoxide should be explored. In children whose hyperinsulinism appears beyond 1 yr of age, surgery is indicated, since an adenoma is likely.


25-gauge transconjunctival sutureless vitrectomy system in the surgical management of children with posterior capsular opacification.
To evaluate the safety and efficacy of the 25-gauge transconjunctival sutureless vitrectomy (TSV) system in the surgical management of posterior capsular opacification (PCO) in pseudophakic children. Pars plana membranectomy was performed for PCO in 10 pseudophakic eyes of six children (mean age 35.1 +/- 37.8 months; range 6-93 months) using the TSV system. Surgical technique, intraoperative problems and postoperative complications including wound leakage, hypotony and the need for suturing were recorded. Wound leakage and other intraoperative problems were not noted in any of the eyes. All eyes showed improvement of visual acuity from a mean of 6/67 before to 6/29 after surgery (P = 0.001). Mean postoperative intraocular pressure (IOP) was 7.8 +/- 3.1 mmHg (range: 3-10 mmHg). Four eyes (40%) had hypotony on the first postoperative day (IOP: 3-5 mmHg), which was transient in three eyes. One eye in a patient with uveitis had persistent hypotony, but hypotony was also present preoperatively, and the postoperative IOP returned to preoperative levels. This eye also developed recurrent PCO and a second capsulotomy was performed using the 25-gauge TSV system. Posterior capsulotomy using the 25-gauge TSV system appears to be a safe and effective approach in the management of PCO in pseudophakic children. Advantages include easier manipulation with the smaller instruments in these small eyes, and it can be considered in appropriate cases.


Motivationally enhanced group counseling for substance users in a soup kitchen: a randomized clinical trial.
Soup kitchens tend to serve residentially unstable adults characterized by a high prevalence of substance abuse. In this study, 289 soup kitchen guests who reported drug or alcohol problems were randomly assigned to information and referral (I&R) plus peer advocacy (peers encouraging subjects to participate in other services) (N = 139) or to an experimental 12-session motivational group (three sessions per week for 4 weeks) followed by a 36-session cognitive-behavioral group (three sessions per week for 12 weeks), plus I&R and peer advocacy. Mean age was 42; 82% male; 68% African-American; 81% unstable residence; 14% HIV+. Experimentals were significantly more likely than the controls to have increased their participation in some type of substance abuse intervention during the follow-up period. In addition, experimentals were significantly more likely than controls to have reduced both drinking and heavy drinking at follow-up (there was no difference between groups in reduction of cocaine use). Interaction analysis indicated that the experimental intervention was more effective for participants with higher rather than lower substance abuse severity at baseline. These results support the concept that motivationally enhanced group counseling, provided as a low-threshold outreach intervention, can help to increase participation in formal treatment and 12-step groups and to reduce substance abuse, particularly for those starting with high severity of use.


Engaging Emergency Nurses in Strategies to Address the Social Determinants of Health.
For patients with social needs, emergency departments can be an essential bridge between the health care system and the community. Emergency nurses' knowledge of and engagement in this work need to be examined to ensure that efforts for social determinants of health screening and the resulting community connections are effective. However, there is limited research in this area of nursing practice. The purpose of this study is to describe emergency nurses' knowledge about social needs in their community, assess their knowledge of existing community resources, and examine their perceived confidence to respond to the social needs of their patients. A cross-sectional survey was conducted with 243 nurses employed in a large regional health care system. Data were collected using an adapted 81-item social determinants of health survey instrument to measure knowledge of social determinants of health, confidence, and frequency of discussing social determinants of health with emergency department patients and awareness of social resources available in the community. Survey participants were asked about barriers to incorporating social determinants of health into their emergency department workflow and to provide general demographic information. Descriptive statistics were used to analyze study results. Most of the 243 emergency nurse participants believed that addressing social determinants of health was important and that emergency nurses should be involved in issues around social determinants of health. However, most nurses reported limited knowledge about social determinants of health and had very limited knowledge about the resources available in their community to help patients with needs related to food, housing, medical care, and transportation. Nurses reported that although they know that their patients are unlikely to ask for help with social needs during an emergency department visit, they are still unlikely to ask their patients about social needs owing to low confidence about having social needs conversations, limited time, and competing care priorities. Participants advocated for greater case manager presence. Feeling connected to the community was significantly correlated to increased knowledge, confidence, and likelihood to ask about social needs (P < .05). The emergency department is a logical place for screening for social determinants of health and connecting patients with social needs to community resources. Emergency nurses included in this study acknowledged that they want to address the social needs of their patients but reported that they lack knowledge about both social determinants of health and more importantly about the resources available to help patients with social needs. In general, they did not feel confident discussing social determinants of health with their patients in the emergency department and are unlikely to ask about social needs. Barriers to screening include time, competing care priorities, and lack of knowledge and support needed from case managers. Findings from this study have implications for supporting emergency nurses employed in institutions that seek to address social influences of health for the patients in their communities.


Nickel-Catalyzed Addition-Type Alkenylation of Unactivated, Aliphatic C-H Bonds with Alkynes: A Concise Route to Polysubstituted γ-Butyrolactones.
Through the nickel-catalyzed chelation-assisted C-H bond activation strategy, the addition-type alkenylation of unreactive β-C(sp(3))-H bonds of aliphatic amides with internal alkynes is developed for the first time to produce γ,δ-unsaturated carboxylic amide derivatives. The resulting alkenylated products can further be transformed into polysubstituted γ-butyrolactones with pyridinium chlorochromate (PCC).


Reduced glycerol incorporation into phospholipids contributes to impaired intra-erythrocytic growth of glycerol kinase knockout Plasmodium falciparum parasites.
Malaria is a devastating disease and Plasmodium falciparum is the most lethal parasite infecting humans. Understanding the biology of this parasite is vital in identifying potential novel drug targets. During every 48-hour intra-erythrocytic asexual replication cycle, a single parasite can produce up to 32 progeny. This extensive proliferation implies that parasites require substantial amounts of lipid precursors for membrane biogenesis. Glycerol kinase is a highly conserved enzyme that functions at the interface of lipid synthesis and carbohydrate metabolism. P. falciparum glycerol kinase catalyzes the ATP-dependent phosphorylation of glycerol to glycerol-3-phosphate, a major phospholipid precursor. The P. falciparum glycerol kinase gene was disrupted using double crossover homologous DNA recombination to generate a knockout parasite line. Southern hybridization and mRNA analysis were used to verify gene disruption. Parasite growth rates were monitored by flow cytometry. Radiolabelling studies were used to assess incorporation of glycerol into parasite phospholipids. Disruption of the P. falciparum glycerol kinase gene produced viable parasites, but their growth was significantly reduced to 56.5±1.8% when compared to wild type parasites. (14)C-glycerol incorporation into the major phospholipids of the parasite membrane, phosphatidylcholine and phosphatidylethanolamine, was 48.4±10.8% and 53.1±5.7% relative to an equivalent number of wild type parasites. P. falciparum glycerol kinase is required for optimal intra-erythrocytic asexual parasite development. Exogenous glycerol may be used as an alternative carbon source for P. falciparum phospholipid biogenesis, despite the lack of glycerol kinase to generate glycerol-3-phosphate. These studies provide new insight into glycerolipid metabolism in P. falciparum.


Risk factors for clinical pregnancy loss after IVF in women with PCOS.
Which factors are associated with the risk of clinical pregnancy loss in women with polycystic ovary syndrome (PCOS) undergoing IVF? Case-control study nested in a multicentre randomized trial comparing live birth rates between fresh and frozen embryo transfer in women with PCOS. Women with the outcome of clinical pregnancy loss were selected as the case group, those with live birth as the control group. Parameters before IVF treatment and variables during ovarian stimulation and embryo transfer were compared. Women with clinical pregnancy loss had higher maternal body mass index (BMI, P = 0.010), anti-Müllerian hormone (AMH, P = 0.032), 2-h glucose concentration after 75 g oral glucose tolerance test (OGTT, P = 0.025), and a higher proportion of fresh embryo transfers (P = 0.001). There were significant interactions between the types of transfer and antral follicle count (AFC, P = 0.013), 2-h glucose concentration after OGTT (P = 0.024) on clinical pregnancy loss in PCOS, indicating that these factors may have different effects on pregnancy loss after fresh versus frozen embryo transfer. When the multivariable logistic regression analysis was stratified by the fresh or frozen embryo transfer, AFC (adjusted odds ratio [aOR] 1.03, 95% confidence interval [CI] 1.01-1.05) was a risk factor for clinical pregnancy loss after fresh embryo transfer, while 2-hour glucose concentration after OGTT (aOR 1.13, 95% CI 1.01-1.25) was associated with clinical pregnancy loss in frozen embryo transfer (FET) cycles. In women with PCOS, fresh embryo transfer, higher BMI, AFC and 2-h glucose concentration after OGTT were risk factors for clinical pregnancy loss. FET may be a better choice to decrease the risk of clinical pregnancy loss, especially for those with higher AFC. During FET, 2-h glucose after OGTT appears to be associated with clinical pregnancy loss and warrants close monitoring.


The price of independence: cell separation in fission yeast.
The ultimate goal of cell division is to give rise to two viable independent daughter cells. A tight spatial and temporal regulation between chromosome segregation and cytokinesis ensures the viability of the daughter cells. Schizosaccharomyces pombe, commonly known as fission yeast, has become a leading model organism for studying essential and conserved mechanisms of the eukaryotic cell division process. Like many other eukaryotic cells it divides by binary fission and the cleavage furrow undergoes ingression due to the contraction of an actomyosin ring. In contrast to mammalian cells, yeasts as cell-walled organisms, also need to form a division septum made of cell wall material to complete the process of cytokinesis. The division septum is deposited behind the constricting ring and it will constitute the new ends of the daughter cells. Cell separation also involves cell wall degradation and this process should be precisely regulated to avoid cell lysis. In this review, we will give a brief overview of the whole cytokinesis process in fission yeast, from the positioning and assembly of the contractile ring to the final step of cell separation, and the problems generated when these processes are not precise.


Semiautomated Ventilation Defect Quantification in Exercise-induced Bronchoconstriction Using Hyperpolarized Helium-3 Magnetic Resonance Imaging: A Repeatability Study.
This study aimed to compare the performance of a semiautomated ventilation defect segmentation approach, adaptive K-means, with manual segmentation of hyperpolarized helium-3 magnetic resonance imaging in subjects with exercise-induced bronchoconstriction (EIB). Six subjects with EIB underwent hyperpolarized helium-3 magnetic resonance imaging and spirometry tests at baseline, post exercise, and recovery over two separate visits. Ventilation defects were analyzed by two methods. First, two independent readers manually segmented ventilation defects. Second, defects were quantified by an adaptive K-means method that corrected for coil sensitivity, applied a vesselness filter to estimate pulmonary vasculature, and segmented defects adaptively based on the overall low-intensity signals in the lungs. These two methods were then compared in four aspects: (1) ventilation defect percent (VDP) measurements, (2) correlation between spirometric measures and measured VDP, (3) regional VDP variations pre- and post exercise challenge, and (4) Dice coefficient for spatial agreement. The adaptive K-means method was ~5 times faster, and the measured VDP bias was under 2%. The correlation between predicted forced expiratory volume in 1 second over forced vital capacity and VDP measured by adaptive K-means (ρ = -0.64, P <0.0001) and by the manual method (ρ = -0.63, P <0.0001) yielded almost identical 95% confidence intervals. Neither method of measuring VDP indicated apical/basal or anterior dependence in this small study cohort. Compared to the manual method, the adaptive K-means method provided faster, reproducible, comparable measures of VDP in EIB and may be applied to a variety of lung diseases.


Parathyroid carcinoma: impact of preoperative diagnosis on the choice of surgical procedure.
The operative procedure in the surgical treatment of parathyroid carcinoma differs from that of benign hyperparathyroidism. However, preoperative differentiation is often difficult. This study elucidated how clinicians diagnose parathyroid carcinoma and the relationship between preoperative diagnosis and the operative course. Using a retrospective chart review, twenty cases of parathyroid carcinoma from nine participating centers were examined. In 11 cases with preoperative suspicion of malignancy, at least one of these three features was found: elevated serum calcium level (>14 mg/dL), palpable mass, and irregular margin on ultrasonography. Although an intact parathyroid hormone (iPTH) threshold to suspect malignancy has not been established, six cases showed marked iPTH elevation exceeding 8.0 times the upper limit of normal. One case was excluded from analysis due to hemodialysis. Compared with the four cases that showed calcium elevation, the iPTH threshold might represent better sensitivity. Among 9 cases of benign preoperative diagnosis, six cases were performed with pericapsular resection. In three cases where malignancy was suspected in the middle of the operation, the recommended en bloc resection with ipsilateral thyroid lobectomy was not performed but a parathyroidectomy with surrounding soft tissue. In contrast, 10 preoperatively suspected cases underwent en bloc resection, and one case underwent pericapsular resection followed by supplementary ipsilateral hemithyroidectomy due to the uncertain pre- and intraoperative findings to determine the diagnosis. In conclusion, the surgical procedure for parathyroid carcinoma strongly depends on the preoperative diagnosis. The presence of excessive iPTH levels might contribute to improved preoperative diagnostic sensitivity for parathyroid carcinoma.


Predictive and prognostic effect of computed tomography-derived body composition analysis during neoadjuvant chemotherapy for operable and locally advanced breast cancer.
Excess adiposity is associated with several factors involved in carcinogenesis and breast cancer progression. Evidence supporting the role of body composition in breast cancer treatment is promising, but still scanty and mainly focused on adjuvant treatment. The aim of this study was to evaluate the changes in body composition during neoadjuvant chemotherapy and its association with pathologic complete response and survival outcome in patients treated for operable/locally advanced breast cancer. A retrospective review of patients with breast cancer treated with neoadjuvant chemotherapy was performed in the Oncology Section of the Department of Medicine, University of Verona between 2014 and 2019. Body composition was evaluated from clinically acquired computed tomography scans at diagnosis and after neoadjuvant chemotherapy. Descriptive statistic was adopted. The associations of body composition measures with pathologic complete response and disease-free survival were analyzed. Kaplan-Meier curves were compared with log-rank analysis. Data from 93 patients were collected. After neoadjuvant chemotherapy, the adipose compound changed significantly across all body mass index categories. Body composition parameters had no significant effect on pathologic complete response. Survival analysis showed that a high gain of visceral adipose tissue during neoadjuvant chemotherapy was associated with shorter disease-free survival (hazard ratio, 10.2; P = 0.026). In particular, disease-free survival was significantly worse in patients who gained ≥10% of visceral adipose tissue compared with patients who gained <10% of visceral adipose tissue (5-y disease-free survival 71.4 versus 96.3, P = 0.009, respectively). Our results indicated that neoadjuvant chemotherapy significantly affects body composition, which seems to have an effect on survival outcome of breast cancer, highlighting the relevance of the body composition assessment when estimating treatment outcomes.


Headache and migraine.
The application of modern imaging techniques to the study of patients with headache/migraine has dramatically changed our understanding of these conditions. Several studies of these patients have demonstrated not only the occurrence of abnormalities of function, but also relevant and diffuse structural changes of the brain white and grey matter. More recently, it has been suggested that the different forms of headache/migraine might have specific functional and structural MRI correlates, which, in the future, is likely to result in new therapeutic scenarios.


A phase I/II study of doxorubicin, ifosfamide, etoposide and interval methotrexate in patients with poor prognosis osteosarcoma.
The prognosis for patients with metastatic or axial-skeletal osteosarcoma is poor. A phase I/II study was conducted of intensive chemotherapy with interval methotrexate, to assess the feasibility, response rate and toxicity in this group of patients. Thirteen patients, median age 18 (range: 8-34), with metastatic or axial-skeletal osteosarcoma were treated with ifosfamide 2.5 g/m(2), etoposide 150 mg/m(2), and doxorubicin 20 mg/m(2) on days 1-3, every 21 days, with interval methotrexate 12 g/m(2) given on day 14, for a maximum of eight cycles. Surgery to the primary was considered after four cycles for those with operable disease, or together with metastatic disease at completion of chemotherapy in those with inoperable tumours. A total of 85 cycles were given, median 6 per patient (range: 4-8). Only 6 of the 13 patients completed all 8 cycles of chemotherapy. Forty-eight cycles (56%) required a dose reduction. The principal toxicity was myelosuppression, with a median nadir neutrophil count of 0.1 (range: 0-4.1). Grade 3 or 4 infection was seen in 41 cycles (48%). Histological response was assessable in seven patients, all of whom achieved a >or=90% necrosis. Radiological response rate, evaluable in seven patients with lung metastases, was 43%. All but one patient has had subsequent disease progression or relapse, with a median event free survival of 13 months (range: 5-53). This regimen was associated with responses, but these were not sustained. Substantial toxicity was seen, preventing optimal delivery. More effective, less toxic regimens are needed in this group of patients.


Isolation of an adeno associated virus from sheep. Brief report.
An adenovirus and a spherical virus 20--24 nm diameter were isolated from ovine faeces. The small virus replicated in the nucleus, and was associated especially with the nucleolus. It haemagglutinated guinea pig and human erythrocytes, was thermostable and required an adenovirus for replication. It is concluded that this represents the first recorded isolate of an ovine AAV.


Value of high resolution real-time ultrasonography in secondary hyperparathyroidism.
Thirty-two patients were treated surgically for symptomatic secondary or tertiary hyperparathyroidism, and 27 of these patients had high resolution (10 mHz) real-time ultrasonography before parathyroidectomy. This preoperative localization study identified one or more enlarged hyperplastic parathyroid glands in all but one patient who had not had a previous parathyroid operation, and in five of six patients who did have previous parathyroid operations. In both of the patients in whom no parathyroid glands were identified by ultrasonography the only abnormal enlarged parathyroid glands were those situated within the superior mediastinum. When large glands are not observed by ultrasonography in patients with severe secondary hyperparathyroidism, the glands are usually situated in the superior mediastinum, behind the trachea or esophagus, or deeply within the neck. The size of the parathyroid glands correlated positively with the serum parathyroid hormone level and with the severity of the secondary hyperparathyroidism. Thus, the preoperative identification of parathyroid glands by ultrasonography not only localizes the site of most hyperplastic parathyroid glands (70 percent of patients), but also detects those patients who have enlarged parathyroid glands, elevated serum parathyroid hormone levels, and severe secondary hyperparathyroidism. These are the patients who are thus unlikely to respond to further medical therapy.


Changes in sugar content and activity of vacuolar acid invertase during low-temperature storage of potato tubers from six Japanese cultivars.
The storage of potato tubers at low temperatures leads to the accumulation of sugars in a process called "low-temperature sweetening." To understand this phenomenon, we measured the sugar contents and the activity of acid invertase over several months in tubers of six Japanese cultivars stored at 4 degrees C or 20 degrees C. At 20 degrees C, few changes in sugar contents took place in any of the tubers. On the other hand, when stored at 4 degrees C, three types of changes were observed among the cultivars: (1) increased levels of reducing sugars during storage; (2) a pattern similar to that of type 1, but with 4- to 6-fold lower levels of reducing sugars throughout storage; and (3) increased sucrose, but not reducing sugars. The activity of vacuolar acid invertase increased in the type-1 cultivars, whereas, in the type-2 and type-3 cultivars, the activities were very low during storage at 4 degrees C. Reverse transcription-polymerase chain reaction analysis of acid invertase showed that the transcripts of the enzyme accumulated in the tubers stored at 4 degrees C in the type-1 cultivars but not in type-3. These results suggest that the activity of vacuolar acid invertase is related to the types of changes that occurred in sugar content during low-temperature storage among the potato cultivars.


Intravenous Hydration for Management of Medication-Resistant Orthostatic Intolerance in the Adolescent and Young Adult.
Orthostatic intolerance (OI) is common in teenagers (T) and young adults (A). Despite treatment with oral fluids, medication, and exercise, a significant number have symptoms from multiple organ systems and suffer low quality of life (QOL). Previous studies showed that acute intravenous (IV) hydration (IH) could help restore orthostatic tolerance; however, no data are available about the intermediate-term effects of IH. We therefore studied the efficacy of IH to improve QOL and manage medication-refractory OI patients. Our study population consisted of 39 patients (mean age = 16.1 ± 3.3) years; thirty-two were female. Average number of medications failed = 3.1. Average QOL score on self-reported OI questionnaire was 4.2 (normal QOL = 10). IV hydration consisted of normal saline (1-2 l/day, 3-7 days/week). 1) Orthostatic testing revealed Postural Orthostatic Tachycardia (24), Neurally Mediated Hypotension (14) or OI (1). 2) Average orthostatic change in heart rate was 48 ± 18 bpm. 3) IH was performed via intermittent IV access (10), PICC line (22), and Port (7). 4) Duration of IH varied from 1 week to 3.8 years (mean = 29 ± 47 weeks). 5) Overall, 79 % (n = 31) demonstrated clinically improved self-reported QOL. 6) Six patients who discontinued IH requested to restart treatment. (7) Complications consisted of upper extremity deep vein thrombosis (n = 3) and infection (n = 4). IH is an effective therapy to improve QOL in T&A with medication-resistant OI. Most patients continued to report improved QOL once IH was discontinued. IH should be considered a therapeutic option in medication-resistant OI patients with low QOL.


Objectively-measured physical activity in New Zealand workers.
To date, no objective measurements of New Zealanders' physical activity have been reported. The relative contribution of work time activity to total daily physical activity by gender and occupational category has also not been measured objectively in any population. The present study reports such data using pedometer steps counts to quantify both work and non-work physical activity in a sample of New Zealand adult workers in six different occupational categories over a three-day period. Females (9943+/-3855 steps) had slightly higher, but not significantly different (F=0.084(1,179)1, p=0.772) daily step counts than males (9766+/-3965 steps). Using the 10 000 steps a day criterion, 57% of the sample were considered at least low-active. Analysis of variance was used to identify between group (occupational) differences in workplace physical activity (F=11.189(5,175), p<0.001), non-work physical activity (F=2.596(5.175), p=0.027), and total physical activity (F=6.265(5,175), p<0.001). Tukey post hoc comparisons showed significant differences with retail and blue collar workers achieving higher activity levels in comparison to the other occupational categories in work and total physical activity. Odds ratios were calculated to find the odds of being in the top half of activity classification for work and non-work physical activity by tertile splits of work time, active transportation use, sport and exercise participation, television and computer viewing, and passive recreation. Active transportation and passive recreation were related to increased odds of higher work pedometer steps. For non-work pedometer values, television and computer use increased the likelihood of being in the lowest activity group, while sport and exercise participation were associated with increased activity levels.


Is intracellular ice formation the cause of death of mouse sperm frozen at high cooling rates?
Mouse spermatozoa in 18% raffinose and 3.8% Oxyrase in 0.25 x PBS exhibit high motilities when frozen to -70 degrees C at 20-130 degrees C/min and then rapidly warmed. However, survival is <10% when they are frozen at 260 or 530 degrees C/min, presumably because, at those high rates, intracellular water cannot leave rapidly enough to prevent extensive supercooling and this supercooling leads to nucleation and freezing in situ (intracellular ice formation [IIF]). The probability of IIF as a function of cooling rate can be computed by coupled differential equations that describe the extent of the loss of cell water during freezing and from knowledge of the temperature at which the supercooled protoplasm of the cell can nucleate. Calculation of the kinetics of dehydration requires values for the hydraulic conductivity (Lp) of the cell and for its activation energy (Ea). Using literature values for these parameters in mouse sperm, we calculated curves of water volume versus temperature for four cooling rates between 250 and 2000 degrees C/min. The intracellular nucleation temperature was inferred to be -20 degrees C or above based on the greatly reduced motilities of sperm that underwent rapid cooling to a minimum temperature of between -20 and -70 degrees C. Combining that information regarding nucleation temperature with the computed dehydration curves leads to the conclusion that intracellular freezing should occur only in cells that are cooled at 2000 degrees C/min and not in cells that are cooled at 250-1000 degrees C/min. The calculated rate of 2000 degrees C/min for IIF is approximately eightfold higher than the experimentally inferred value of 260 degrees C/min. Possible reasons for the discrepancy are discussed.


Lacunar infarction in type 2 diabetes is associated with an elevated intracranial arterial pulsatility index.
The arterial pulsatility index (PI) is measured by transcranial Doppler ultrasonography (TCD) and is postulated to reflect the vascular resistance distal to the artery being examined. An increased PI of the intracranial artery is often reported with diabetes mellitus (DM), old age, hypertension, intracranial hypertension, vascular dementia, and small artery disease. Microvascular complication of DM, which may contribute to cerebral infarction, involves the small perforating artery and may influence the PI of the proximal artery. We performed a TCD examination in patients with type 2 DM with acute lacunar infarction (DML, n=35), type 2 DM without cerebral infarction (DMO, n=69), and in control cases with no DM or cerebral infarction (control group, n=41). We then compared the TCD findings among these groups. The PI was significantly higher in the DML and DMO groups than in the control group (1.05, 0.93, 0.73. respectively, for the right middle cerebral artery; 1.04, 0.90, 0.73, respectively, for the left middle cerebral artery; 0.97, 0.89, 0.70, respectively, for the basilar artery). The PI was also significantly higher in the DML group than in the DMO group for both middle cerebral arteries. The flow velocity was comparable among the three groups. The elevated PI of the intracranial arteries may reflect diabetic cerebral microvascular complications. The PI measurement using TCD may be a useful predictor of lacunar infarction in type 2 DM patients.


Evidence for a plasma inhibitor of the heparin accelerated inhibition of factor Xa by antithrombin III.
The ability of heparin fractions of different molecular weight to potentiate the action of antithrombin III against the coagulation factors thrombin and Xa has been examined in purified reaction mixtures and in plasma. Residual thrombin and Xa have been determined by their peptidase activities against the synthetic peptide substrates H-D-Phe-Pip-Arg-pNA and Bz-Ile-Gly-Arg-pNA. High molecular weight heparin fractions were found to have higher anticoagulant activities than low molecular weight heparin when studied with both thrombin and Xa incubation mixtures in purified mixtures and in plasma. The inhibition of thrombin by heparin fractions and antithrombin III was unaffected by other plasma components. However, normal human plasma contained a component that inhibited the heparin and antithrombin III inhibition of Xa particularly when the high molecular weight heparin fraction was used. Experiments using a purified preparation of platelet factor 4 suggested that the platelet-derived heparin-neutralizing protein was not responsible for the inhibition.


A simple method for the preparation of human serum albumin.
A simple method, based on ethanol fractionation, for the preparation of highly purified human serum albumin with a higher yield than that of the conventional ethanol procedures is described. It consists of two purification steps, namely, precipitation of most of the other plasma proteins from a 3-fold diluted plasma with ethanol at 42% concentration, pH 5.75 and -5 degrees C, leaving over 96% pure albumin in the supernatant, followed by isoelectric precipitation of albumin from the supernatant at pH 4.8 and -5 degrees C. The paste thus obtained was processed to the final albumin solution according to the conventional methods. The yield of the final albumin with a purity of over 99% was equivalent to 29.5 g/l of plasma representing a recovery of over 93%. The possibility of recovering other plasma proteins and the suitability for large scale preparation are also discussed.


High mass loading paper-based electrode material with cellulose fibers under coordination of zirconium oxyhydroxide nanoparticles and sulfosalicylic acid.
With the rapid expansion of the flexible electronics market, it is critical to develop high-performance flexible energy storage electrode materials. Cellulose fibers, which are sustainable, low cost, and flexible, fully meet the requirements of flexible electrode materials, but they are electrically insulating and cause a decrease in energy density. In this study, high-performance paper-based flexible electrode materials (PANI:SSA/Zr-CFs) were prepared with cellulose fibers and polyaniline. A high mass loading of polyaniline was wrapped on zirconia hydroxide-modified cellulose fibers under metal-organic acid coordination through a facile in situ chemical polymerization process. The increase in mass loading of PANI on cellulose fibers not only improves the electrical conductivity but also enhances the area-specific capacitance of the flexible electrodes. The results of electrochemical tests show that the area specific capacitance of the PANI:SSA/Zr-CFs electrode is 4181 mF/cm2 at 1 mA/cm2, which is more than two times higher than that of the electrode with PANI on pristine CFs. This work provides a new strategy for the design and manufacture of high-performance flexible electronic electrodes based on cellulose fibers.


Rous sarcoma virus-induced changes in the pattern of phosphorylation of non-histone nuclear proteins.
We here studied the protein kinase activity and in vitro phosphorylable sites of non-histone nuclear proteins, 0.4 M NaCl extracts (mostly chromosomal proteins) from chick embryo fibroblasts (CEF), infected or not with a Schmidt Ruppin strain subgroup A of Rous sarcoma virus (RSV). The infection and transformation of chick fibroblasts by RSV induced an increase in kinase activity and endogenous phosphorylation of non-histone chromosomal (NHC) proteins. The stimulation, by a change of medium, of the proliferation of dense cultures of normal chick fibroblasts also induced an increase in the kinase activity and endogenous phosphorylation of NHC proteins. However, two-dimensional gel electrophoresis of the 32P-phosphorylated proteins showed that stimulation due to a change of medium and that due to the expression of transformation were very different. The stimulation by a change of medium increased to a greater or lesser extent the phosphorylation of the different NHC proteins, with no fundamental variations in the pattern of protein phosphorylation. In contrast, RSV infection induced significant changes in the pattern of protein phosphorylation. One of the most striking feature was the large increase of amount and phosphorylation of high molecular weight (HMW) proteins in particular of phosphoproteins having an evaluated molecular weight (MW) of 78 K and 82 K and pI greater than 8.2. The percent of phosphotyrosine residues in NHC proteins was clearly increased when the proteins were extracted from transformed cells instead of normal cells. But the alkaline treatment of two-dimensional gel electrophoresis indicated that the 80 K phosphoproteins did not contain phosphotyrosine residues, and thus cannot be considered as substrates for pp60src kinase.


Dipeptidyl peptidase 4 inhibitor attenuates obesity-induced myocardial fibrosis by inhibiting transforming growth factor-βl and Smad2/3 pathways in high-fat diet-induced obesity rat model.
Obesity-induced myocardial fibrosis may lead to diastolic dysfunction and ultimately heart failure. Activation of the transforming growth factor (TGF)-βl and its downstream Smad2/3 pathways may play a pivotal role in the pathogenesis of obesity-induced myocardial fibrosis, and the antidiabetic dipeptidyl peptidase 4 inhibitors (DPP4i) might affect these pathways. We investigated whether DPP4i reduces myocardial fibrosis by inhibiting the TGF-β1 and Smad2/3 pathways in the myocardium of a diet-induced obesity (DIO) rat model. Eight-week-old male spontaneously hypertensive rats (SHRs) were fed either a normal fat diet (chow) or a high-fat diet (HFD) and then the HFD-fed SHRs were randomized to either the DPP4i (MK-0626) or control (distilled water) groups for 12weeks. At 20weeks old, all the rats underwent hemodynamic and metabolic studies and Doppler echocardiography. Compared with the normal fat diet (chow)-fed SHRs, the HFD-fed SHRs developed a more intense degree of hyperglycemia and dyslipidemia and showed a constellation of left ventricular (LV) diastolic dysfunction, and exacerbated myocardial fibrosis, as well as activation of the TGF-β1 and Smad2/3 pathways. DPP4i significantly improved the metabolic and hemodynamic parameters. The echocardiogram showed that DPP4i improved the LV diastolic dysfunction (early to late ventricular filling velocity [E/A] ratio, 1.49±0.21 vs. 1.77±0.09, p<0.05). Furthermore, DPP4i significantly reduced myocardial fibrosis and collagen production by the myocardium and suppressed TGF-β1 and phosphorylation of Smad2/3 in the heart. In addition, DPP4i decreased TGF-β1-induced collagen production and TGF-β1-mediated phosphorylation and nuclear translocation of Smad2/3 in rat cardiac fibroblasts. In conclusion, DPP4 inhibition attenuated myocardial fibrosis and improved LV diastolic dysfunction in a DIO rat model by modulating the TGF-β1 and Smad2/3 pathways.


(137)Cs concentration in zooplankton and its relation to taxonomic composition in the western North Pacific Ocean.
To study the role of zooplankton in the transport of (137)Cs in the ocean, zooplankton samples were collected in October 2005 and June 2006 in the western North Pacific Ocean. The peak zooplankton biomass was observed in the surface layer, and gelatinous plankton was more abundant in October 2005 than in June 2006 reflecting exchange of water masses. The concentrations of (137)Cs in zooplankton varied from 11 to 24 mBq kg wet(-1) and were higher in October 2005 than in June 2006. The elevated abundance of gelatinous zooplankton probably led to higher concentration of (137)Cs in zooplankton in October 2005. Annual export fluxes of (137)Cs by ontogenetic vertical migrant copepods were estimated to be 0.8 and 0.6 mBq m(-2) year(-1) at 200 and 1000 m depths, respectively; this suggested that transport of (137)Cs by zooplankton may be no trivial pathway.


A multicenter, phase II trial of GC1118, a novel anti-EGFR antibody, for recurrent glioblastoma patients with EGFR amplification.
We evaluated the therapeutic efficacy of GC1118, a novel anti-epidermal growth factor receptor (EGFR) monoclonal antibody, in recurrent glioblastoma (GBM) patients with EGFR amplification. This study was a multicenter, open-label, single-arm phase II trial. Recurrent GBM patients with EGFR amplification were eligible: EGFR amplification was determined using fluorescence in situ hybridization analysis when a sample had both the EGFR/CEP7 ratio of ≥2 and a tight cluster EGFR signal in ≥10% of recorded cells. GC1118 was administered intravenously at a dose of 4 mg/kg once weekly. The primary endpoint was the 6-month progression-free survival rate (PFS6). Next-generation sequencing was performed to investigate the molecular biomarkers related to the response to GC1118. Between April 2018 and December 2020, 21 patients were enrolled in the study and received GC1118 treatment. Eighteen patients were eligible for efficacy analysis. The PFS6 was 5.6% (95% confidence interval, 0.3%-25.8%, Wilson method). The median progression-free survival was 1.7 months (range: 28 days-7.2 months) and median overall survival was 5.7 months (range: 2-22.0 months). GC1118 was well tolerated except skin toxicities. Skin rash was the most frequent adverse event and four patients experienced Grade 3 skin-related toxicity. Genomic analysis revealed that the immune-related signatures were upregulated in patients with tumor regression. This study did not meet the primary endpoint (PFS6); however, we found that immune signatures were significantly upregulated in the tumors with regression upon GC1118 therapy, which signifies the potential of immune-mediated antitumor efficacy of GC1118.


Serum osteopontin predicts glycaemic profile improvement in metabolic syndrome: A pilot study.
Prediabetes is often observed in patients with Metabolic Syndrome (MetS) and might be associated with metabolic and inflammatory alterations. Here, we investigated whether the inflammatory molecule osteopontin (OPN) might have a prognostic impact in a cohort of MetS patients (n = 85) with baseline normal glycaemia or impaired fasting glucose (IFG) over one year of recommended pharmacological treatments and Mediterranean diet. Patients were then followed up for 12 months with intermediate evaluation after 6 months. At all time points, anthropometric and clinical data were recorded, alongside with haematological and biochemical profiles, including serum concentrations of OPN. As expected, Mediterranean diet improves glycaemic profile in patients with IFG. Baseline serum OPN failed to be associated with baseline anthropometric or biochemical variables. At baseline, higher levels of OPN were shown in patients with IFG as compared to normal glycaemia. Two distinct subgroups of patients in whom OPN decreased or remained stable/increased at follow-up were identified. When higher serum OPN levels were observed at baseline, greater reduction was observed at 1-year follow-up. Reduction in circulating OPN levels was associated with metabolic improvement in terms of blood pressure, LDL-c, HDL-c, and glycaemia. At both univariate and adjusted logistic regression analyses, serum OPN emerged as an independent predictor of glycaemic profile improvement at 1-year follow-up (adjOR 1.05 [1.00-1.10]; P = .041). In conclusion, pharmacological and dietetic interventions improved glycaemic profile in patients with MetS. In particular, glycaemic improvement was demonstrated in patients who also reduce circulating OPN levels. Higher OPN levels at baseline predict normalization of glycaemic profile.


Laparoscopic adrenalectomy for metachronous metastasis from renal cell carcinoma.
Metachronous adrenal metastases (AM) from renal cell carcinoma (RCC) are rare. We report our experience of surgical resection in this setting, with particular respect to laparoscopic approach and long-term outcome. A retrospective review of 11 patients who underwent adrenalectomy for metachronous AM from RCC was conducted between 2002 and 2005 in a tertiary referral center. CT scan findings were those of an adrenal mass ranging from 2 to 13 cm in diameter with a basal density of 12 to 28 Hounsfield Units and strong heterogeneous enhancement following contrast injection. The surgical procedure consisted of controlateral (n = 5), ipsilateral (n = 2), and bilateral (n = 1) laparoscopic adrenalectomy, whereas three patients underwent controlateral open adrenalectomy for adrenal mass >10 cm. Nine patients were recurrence-free with a median follow-up of 34 months. In the remaining two patients, lung metastases were discovered at postoperative months 28 and 11, respectively. The former patient is alive and free of disease recurrence 32 months after lung metastasis resection, whereas the latter is currently being treated with sunitinib. This study confirms that prolonged overall and disease free-survival can be achieved in selected patient after laparosocpic adrenalectomy for AM from RCC.


Repeated sauna therapy improves myocardial perfusion in patients with chronically occluded coronary artery-related ischemia.
Repeated low-temperature sauna (Waon) therapy relieves ischemic symptoms in patients with peripheral arterial disease. We investigated whether Waon therapy could improve myocardial perfusion in patients with ischemia related to chronic total occlusion (CTO) of coronary arteries. Twenty-four patients who had ischemia in the CTO-related area were examined. The severity of ischemia was quantified by thallium-201 myocardial perfusion scintigraphy with adenosine. The Waon group (n=16) was treated daily for three weeks with a 60 °C far infrared-ray dry sauna bath for 15 min and then kept in a bed covered with blankets for 30 min. The control group (n=8) underwent myocardial perfusion scintigraphy twice with a three-week interval. In the control group, neither summed stress score (SSS) nor summed difference score (SDS) of myocardial scintigraphy changed. However, Waon therapy improved both SSS (16 ± 7 to 9 ± 6, p<0.01) and SDS (7 ± 4 to 3 ± 2, p<0.01), and the improvement was greater in patients with higher SSS and SDS scores at the baseline. Waon therapy extended treadmill exercise time (430 ± 185 to 511 ± 192s, p<0.01) and improved flow-mediated dilation of the brachial artery (4.1 ± 1.3 to 5.9 ± 1.8%, p<0.05), but tended to decrease the number of circulating CD34-positive bone marrow-derived cells. Waon therapy improves CTO-related myocardial ischemia in association with improvement of vascular endothelial function. This therapy could be a complementary and alternative tool in patients with severe coronary lesions not suitable for coronary intervention.


Structural characterization of lignin and lignin-carbohydrate complex (LCC) of sesame hull.
In the present study, lignin and lignin-carbohydrate complex (LCC) constituting the cell wall structure of sesame hulls were investigated to explore novel techniques of dehulling. Milled wood lignin (MWL), Björkman LCC, and acid-soluble LCC (LCC-AcOH) were extracted from sesame hulls and characterized by carbohydrate composition analysis, molecular weight analysis, UV-vis spectroscopy, FT-IR, thermal analysis, Py-GC/MS, 2D HSQC NMR, and 31P NMR. The results showed that rhamnose accounted for the largest proportion of the lignin and LCC fractions, followed by glucose. Björkman LCC had the largest molecular weight, MWL had the smallest molecular weight, and LCC-AcOH had the largest polydispersity index. The lignin of sesame hulls consisted of syringyl (S), guaiacyl (G), p-hydroxyphenyl (H), and caffeyl alcohol (C) units. The most abundant monomer was guaiacyl (G), followed by caffeyl alcohol (C). C-type lignin is a new type of lignin that is different from the three traditional lignin monomers. The major lignin-linked bonds in the MWL and LCC-AcOH were β-O-4' and β-β', and β-5' bonds were present in the Björkman LCC. The major LCC chemical bonds in the three fractions were PhGly. These findings will provide the factual basis for exploring different dehulling methods to enhance the quality of sesame products.


Foliar nitrogen application from veraison to preharvest improved flavonoids, fatty acids and aliphatic volatiles composition in grapes and wines.
This study investigated the effects of foliar nitrogen application from veraison to preharvest (FNVH) on flavonoids, fatty acids and aliphatic volatiles in Cabernet Sauvignon grapes and wines. Solutions with 69 and 138 mg N/plant phenylalanine (P1 and P2, respectively), 69 and 138 mg N/plant urea (U1 and U2, respectively), as well as an aqueous solution without nitrogen (CK), were sprayed three times from veraison to preharvest. U1, P1 had the highest anthocyanins and acylated anthocyanins contents in grapes, respectively. U1 and P2 showed great potential to promote the accumulation of flavonols and flavanols in grapes and wines. U2 increased the contents of almost all free aliphatic volatiles in grapes, while it didn't affect the undesirable smell, and increased the concentrations of fruity esters in wines instead. The study showed FNVH was a useful fertilization way for improving contents of flavonoids and fruity aroma in grapes and wines in deficit-nitrogen vineyards.


Angiogenic factors in atrial fibrillation: a possible role in thrombogenesis?
The precise pathophysiological processes underlying the prothrombotic or hypercoagulable state in atrial fibrillation (AF) remain uncertain. We hypothesized a relationship between abnormal endothelial damage/dysfunction, coagulation, and angiogenic factors, thereby contributing to increased thrombogenicity. Plasma levels of von Willebrand factor (vWF, an index of endothelial damage/dysfunction) and tissue factor (TF, an index of coagulation), as well as the angiogenic factors, vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), were measured by enzyme-linked immunosorbant assay (ELISA) in 59 chronic AF patients. Data were compared to 40 age- and sex-matched healthy controls in sinus rhythm. Plasma vWF, VEGF and Ang-2 were significantly higher in AF patients compared to healthy controls (P=0.005, P=0.0055 and P<0.0001 respectively) but there were no significant differences in plasma Ang-1 or TF levels between the two groups (P=0.925 and P=0.121 respectively). Significant correlations were found between VEGF and vWF levels (Spearman, r=0.262, P=0.011) and between VEGF and Ang-2 (r=0.333, P=0.001). Raised VEGF in association with Ang-2 and vWF may reflect a link between abnormal endothelial damage/dysfunction and angiogenic factors. These may act together to alter TF expression and endothelial integrity, thereby contributing to the prothrombotic state in AF.


Effect of nitric oxide treatment on pork meat quality, microstructure, and total bacterial count during postmortem aging.
In this paper, the potential effect of nitric oxide (NO) on improving the fresh meat quality of pork was primarily investigated by treatment of longissimus thoracis (LT) with 0, 20, 40, 60, 80 μL/L NO gas within 6 h post-slaughter. After the NO treatments were completed, the pork chops were vacuum-packaged and stored at 4 °C for 1, 4, and 7 d. Compared with the control group, NO treatment enhanced ultimate pH and a* value, and decreased the total bacterial count. The meat treated with 40 and 60 μL/L NO presented higher water holding capacity (WHC), lower shear force and meat hardness with more unconsolidated muscle cell structure. Though 80 μL/L NO treatment achieved better color and microbial attributes, it had a negative effect on WHC and tenderness. Our data suggest that NO treatment is able to improve pork meat quality in a dose-dependent manner.


Using glucaminium-based ionic liquids for improving the separation of 2-aminopyrimidine-5-ylboronic acid and its pinacol ester by high performance liquid chromatography.
A reversed-phase high performance liquid chromatography (HPLC) method is described for the determination of boronic acids that are commonly present as impurities in pinacolboronate ester reagents. Boronic acids and their pinacolboronate esters are key reagents in the Suzuki-Miyaura coupling reaction. The retention of hydrophilic boronic acids in reversed-phase chromatography is often a challenge, especially in very high pH mobile phases, which are needed to mitigate the on-column degradation of pinacolboronate esters. In this study, a hydrophilic boronic acid, 2-aminopyrimidine-5-ylboronic acid, was complexed with specifically functionalized glucaminium-based ionic liquids that were added to the diluent. The two glucaminium-based ILs possess cis-diol moieties that are capable of forming complexes with boronic acids. In addition, aromatic functional groups within the glucaminium cation allow strong π-π interactions with the polymeric stationary phase. Using this approach, the limit of detection for 2-aminopyrimidine-5-ylboronic acid was found to be 3-4μM. The quantification of 2-aminopyrimidine-5-ylboronic acid within a 2-aminopyrimidine-5-pinacolboronate ester sample was successfully achieved using this method.


Crystal structure of the protein L-isoaspartyl methyltransferase from Escherichia coli.
Among the known covalent damages that can occur spontaneously to proteins, the formation of isoaspartyl linkages through deamidation of asparagines and isomerization of aspartates may be one of the most rapid forms under conditions of physiological pH and temperature. The protein L-isoaspartyl methyltransferase (PIMT) is thought to recognize L-isoaspartyl residues and repair this kind of damaged proteins. Curiously, there is a potential functional difference between bacterial and mammalian PIMTs. Herein, we present the crystal structure of Escherichia coli PIMT (EcPIMT) at a resolution of 1.8 Å. The enzyme we investigated was able to remain bound to its product S-adenosylhomocysteine (SAH) during crystallization. Analysis indicates that the high affinity of EcPIMT for SAH might lead to the lower activity of the enzyme.


GluN2A versus GluN2B: twins, but quite different.
N-Methyl-D-aspartate receptors (NMDARs) play vital roles in the central nervous system, as they are primary mediators of Ca(2+) influx during synaptic activity. The subunits that compose NMDARs share similar topological structures but are distinct in distribution and pharmacological properties, as well as physiological and pathological functions, which make the NMDAR one of the most complex and elusive ionotropic glutamate receptors. In this review, we focus on GluN2A and GluN2B, the primary NMDAR subunits in the cortex and hippocampus, and discuss their differences in developmental expression, brain distribution, trafficking, and functional properties during neuronal activity.


HPLC retention behaviors of pi-electron rich compounds on Ni2+- and Cu2+-phthalocyanine derivatives bound to silica gels in polar eluents.
The effect of the central metal of columns packed with silica gels binding Ni(2+)- and Cu(2+)-phthalocyanine derivatives (Ni-and Cu-PCS(D)s) on the retention behavior of poly-aromatic-hydrocarbons (PAHs) thereof in a polar eluent was examined. The retention factors of PAHs on the Ni- and Cu-PCS(D)s in 80% methanol showed a good linear correlation. The Cu-PCS(D) column exhibited the pi-pi interactions for PAHs, while the Ni-PCS(D) column exhibited the pi-d interactions for PAHs in addition to the pi-pi interaction for PAHs. Further, an investigation of the retention behavior of anthracene derivatives having different substituents revealed that the Ni- and Cu-PCS(D) columns could recognize the differences of substituents only in a polar eluent.


Arterial Embolisms and Thrombosis in Upper Extremity Ischemia.
Upper extremity ischemia (UEI) is an uncommon condition that can lead to permanent disability. There is a limited understanding of the etiology, management, and outcomes of the disease. We retrospectively reviewed the charts of all patients who were diagnosed with "embolism and/or thrombosis of arteries of upper extremity" at our institution from January 2005 to December 2013. Patients diagnosed with embolisms were older (P < .001), more likely to undergo thromboembolectomy (P < .001), had higher rates of hypertension (P = .001), and had longer lengths of hospital stay (P = .002). There were no significant differences in complications or mortality at 30 days and up to 1 year. At our center, embolism was found to be the most common etiology for UEI followed by thrombosis and stenosis. Patients presented with embolism were older, were more likely to undergo thromboembolectomy, and had higher rates of hypertension and longer hospital stays.


[Overcoming treatment resistance in chronic depression : The role of inpatient psychotherapy].
Chronic depression poses a particular challenge for the psychiatric and psychotherapeutic care system. Owing to high rates of psychiatric comorbidities and multiple pharmacological and psychotherapeutic treatment resistance, novel treatment strategies are urgently required. In this article, we describe the clinical characteristics of chronic and treatment-resistant depression and review the pharmacological and psychotherapeutic treatment options currently available. We focus on the Cognitive Behavioral Analysis System of Psychotherapy (CBASP), the first specific psychotherapy approach to chronic depression. Finally, we discuss the role of psychotherapeutic inpatient programs and stepped care concepts in chronic and treatment-resistant depression.


[Colonorectal adenoma: relationships among histological structure, dimensions of the polyps, and age distribution].
Among 1258 polyps from the lower gastro-intestinal tract removed by rectoscopy or coloscopy and examined histologically there were 744 adenomas, 72% tubular, 27% papillary and 1% villous. 96.5% of all adenomas were extracted from patients aged over 40 years. Four fifths of the tumours were found in the rectum and sigmoid colon. Only 6% of the tubular adenomas were more than 15 mm in diameter, compared with 32% of papillary and 57% of villous adenomas. The special significance of the adenomas lies in their potential malignancy (adenoma-to-cancer sequence).


Massive impairment in executive functions with partial preservation of other cognitive functions: the case of a young patient with severe degeneration of the prefrontal cortex.
Historical bases for the special role of the prefrontal cortex are outlined and the case of a 27-year-old woman with massive bilateral prefrontal damage of unknown etiology is then described. Frontal lobe degeneration was repeatedly examined with magnetic resonance imaging and fluoro-deoxy-D-glucose-positron emission tomography and was found to include both orbital and dorsolateral aspects of the frontal lobes. While the degeneration initially measured was limited to portions of the orbital, medial and dorsolateral parts of both frontal lobes, with right-sided predominance, a second brain scan 15 months later revealed massive shrinkage of both frontal lobes, together with additional involvement of the posterior association cortices. The patient had completed her high-school education and had superior verbal long-term memory, normal short-term memory, and normal priming, but manifested grossly deficient scores in various frontal lobe-sensitive tests. Though a number of neurological examinations were performed, no plausible cause for the damage was established.


Porphyric neuropathy: prevention of progression using haeme-arginate.
We report on a patient with acute intermittent porphyria (AIP) who, during treatment with hypertonic glucose, developed peripheral neuropathy. Once haeme-arginate was started, the progression of the neuropathy was attenuated. This suggests that hypertonic glucose may be inadequate in preventing the development of neuropathy in a patient with porphyria. However, haeme-arginate, if started early, can attenuate the progression of porphyric neuropathy.


Interconversion of Highly Entangled Polyhedra into Concave Polyhedra by Nitrate-Induced Ternary Coordination.
Entangled (M3 L2 )n polyhedral complexes represent a unique class of supramolecular architectures that are stabilized by relatively weak metal-acetylene interactions in cooperation with conventional metal-pyridyl coordination. Counter-anion exchange of these complexes with a nitrate (NO3 - ) ion triggered formal metal insertion between the metal centers, and a heteroleptic ternary coordination mode with acetylenic, pyridyl, and nitrate donors was generated on the metal centers. As a result, the main frameworks of the polyhedral complexes M18 L12 and M12 L8 were formally extended into a new series of concave polyhedra having the compositions M21 L12 and M13 L8 , respectively. This transformation also resulted in the local disconnection of the highly entangled trifurcate topology of the framework, providing clues toward the skeletal editing of extended and complex three-dimensional (3D) architectures.


Protein sample preparation for tissue distribution study.
The distribution and expression level of a protein among animal tissues is indicative of its possible roles. It is important to establish a generally applicable method to prepare protein samples with high-quality and achieve near 100% recovery of proteins from animal tissues. During preparation, to sufficiently dissolve and maintain stability of almost all proteins from tissues, as well as to avoid most contaminations affecting protein detection, 2×SDS Sample Buffer, sonication and trichloroacetic acid precipitation are applied. Here we provide a relatively simple, reproducible, and broadly applicable method for studying protein distribution in most tissues, in which the issues resulting from protein degradation and modification during sample preparation and assay interference by other cellular components like neutral lipids and glycogen could be overcome. Furthermore, this method represents the protein content by equal wet tissue mass, which is a better means to present the expression level of a protein in various tissues. High-quality protein samples from almost all tissues could be prepared. The samples produced are amenable to tissue distribution analysis by Western blotting and for silver/Coomassie staining, proteomics, and other protein analyses, which would contribute to potential biomarkers or treatments for a disease.


Adenine·cytosine substitutions are an alternative pathway of compensatory mutation in angiosperm ITS2.
Compensatory mutations are crucial for functional RNA because they maintain RNA configuration and thus function. Compensatory mutation has traditionally been considered to be a two-step substitution through the GU-base-pair intermediate. We tested for an alternative AC-mediated compensatory mutation (ACCM). We investigated ACCMs by using a comprehensive sampling of ribosomal internal transcribed spacer 2 (ITS2) from 3934 angiosperm species in 80 genera and 55 families. We predicted ITS2 consensus secondary structures by using LocARNA for structure-based alignment and partitioning paired and unpaired regions. We examined and compared the substitution rates and frequencies among base pairs by using RNA-specific models. Base-pair states of ACCMs were mapped onto the inferred phylogenetic trees to infer their evolution. All types of compensatory mutations involving the AC intermediate were observed, but the most frequent substitutions were with AU or GC pairs, which are part of the AU-AC-GC pathway. Compared with the GU intermediate, AC had a lower frequency and higher mutability. Within the AU-AC-GC pathway, the AU-AC substitution rate was much slower than the AC-GC substitution rate. No consistently higher overall rate was identified for either pathway among all 80 sampled lineages, though compensatory mutations through the AC intermediate averaged about half that through the GU intermediate. These results demonstrate an alternative compensatory mutation between AU and GC that helps address the controversial inference of inferred simultaneous double substitutions.