[Role of lipids in regulation of microsomal glucose-6-phosphatase activity after modification of mcirosomes in vivo and in vitro. Effect of phospholipid effectors on the activity of glucose-6-phosphatase].
Modification of microsomal membranes in vivo and in vitro results in changes of the glucose-6-phosphate and inorganic pyrophosphate phosphohydrolase activities of liver microsomal glucose-6-phosphate phosphohydrolase (EC 184.108.40.206). It was demonstrated that the glucose-6-phosphate phosphohydrolase activity of glucose-6-phosphatase depends on the content of phosphatidylethanolamine in the microsomal membranes, whereas the inorganic pyrophosphate phosphohydrolase activity seems to be dependent on the phosphatidylserine content. It is assumed that the regulation of the corresponding enzyme activities by these phospholipids is performed by the same allosteric mechanism in vitro and in vivo.


Eating disorders in a multi-ethnic inner-city UK sample: prevalence, comorbidity and service use.
No studies have investigated the prevalence of eating disorders (ED) according to DSM-5 criteria and few have explored their comorbidity and service use in the general population in the UK. We aimed to estimate the prevalence, comorbidity, and service use in individuals with ED in a multi-ethnic inner city sample. A total of 1698 individuals (age 16/90) were screened for ED in the first phase of the South East London Community Health Study and 145 were followed up with a diagnostic interview. Data was weighed for survey design and Chi Square tests were used to investigate socio-demographic distribution, comorbidity and service use in participants with ED. The point prevalence of ED was 4.4 % (Binge Eating Disorder (BED) 3.6 %; Bulimia Nervosa (BN) 0.8 %) and 7.4 % when including sub-threshold diagnoses (Purging Disorder (PD) 0.6 %; Other Specified Feeding and Eating Disorders (OSFED) 2.4 %). No cases of AN were identified. Purging Disorder was the ED with the highest proportion of comorbid disorders. A minority of participants with ED had accessed specialist care services. ED are common, the comorbidity of ED was in line with previous studies and no ethnic differences were identified. Although PD is not a full diagnosis in DSM-5, we found some evidence of high comorbidity with other disorders, that needs to be replicated using larger samples. Service use was low across ED diagnoses, despite high levels of comorbidity.


OUR FIRST HUNDRED LAPAROSCOPIC CHOLECYSTECTOMIES.
Hundred patients with symptomatic gallstone disease underwent laparosopic cholecystectomy between June 1996 and August 1997. There were 78 females and 22 males, with a mean age of 46.2 (SD 17.8; range 21 to 85) years. The common presentations were right upper abdominal pain (n=66), acute cholecystitis (n=8) and history of jaundice (n=11). Sixteen patients underwent ERCP for suspected CBD stones. Endoscopic papillotomy and basketing cleared the CBD of all calculi in 12. Three patients required conversion to open cholecystectomy because of dense adhesions (n=2) and to control intraoperative haemorrhage (n=1). Mean operating time was 67.2 (SD 39.2; range 22 to 186) minutes. The mean requirement of analgesics was 2.8 (SD 1.3; range 2 to 5) doses and post-operative hospital stay was 1.6 (SD 1.4; range 1 to 7) days. All patients resumed normal activity within 14 days of operation and are well and satisfied with their operation at a median follow up of 8.6 months.


Genetic screen for suppression of transcriptional interference reveals fission yeast 14-3-3 protein Rad24 as an antagonist of precocious Pol2 transcription termination.
Expression of fission yeast Pho1 acid phosphatase is repressed under phosphate-replete conditions by transcription of an upstream prt lncRNA that interferes with the pho1 mRNA promoter. lncRNA control of pho1 mRNA synthesis is influenced by inositol pyrophosphate (IPP) kinase Asp1, deletion of which results in pho1 hyper-repression. A forward genetic screen for ADS (Asp1 Deletion Suppressor) mutations identified the 14-3-3 protein Rad24 as a governor of phosphate homeostasis. Production of full-length interfering prt lncRNA was squelched in rad24Δ cells, concomitant with increased production of pho1 mRNA and increased Pho1 activity, while shorter precociously terminated non-interfering prt transcripts persisted. Epistasis analysis showed that pho1 de-repression by rad24Δ depends on: (i) 3'-processing and transcription termination factors CPF, Pin1, and Rhn1; and (ii) Threonine-4 of the Pol2 CTD. Combining rad24Δ with the IPP pyrophosphatase-dead asp1-H397A allele caused a severe synthetic growth defect that was ameliorated by loss-of-function mutations in CPF, Pin1, and Rhn1, and by CTD phospho-site mutations T4A and Y1F. Rad24 function in repressing pho1 was effaced by mutation of its phosphate-binding pocket. Our findings instate a new role for a 14-3-3 protein as an antagonist of precocious RNA 3'-processing/termination.


Antibiotic treatment targeting gram negative bacteria prevents neratinib-induced diarrhea in rats.
Neratinib is a pan-ErbB tyrosine kinase inhibitor used for extended adjuvant treatment of HER2-positive breast cancer. Diarrhea is the main adverse event associated with neratinib treatment. We aimed here to determine whether antibiotic-induced gut microbial shifts altered development of neratinib-induced diarrhea. Female Albino Wistar rats (total n = 44) were given antibiotics (vancomycin, neomycin, or a cocktail of vancomycin, neomycin and ampicillin) in drinking water for four weeks, and then treated daily with neratinib (50 mg/kg) for 28 days. Diarrhea, along with markers of gastrointestinal damage and microbial alterations were measured by histopathology and 16S sequencing, respectively. Rats treated with vancomycin or neomycin had significantly lower levels of diarrhea than rats treated with neratinib alone. In the distal ileum, neratinib was associated with a statistically significant increase in histological damage in all treatment groups expect the antibiotic cocktail. Key features included villous blunting and fusion and some inflammatory infiltrate. Differences in microbial composition at necropsy in vehicle control, neratinib and neratinib + neomycin groups, were characterized by a neratinib-induced increase in gram-negative bacteria that was reversed by neomycin. Neomycin shifted bacterial composition so that Blautia become the dominant genus. Narrow spectrum antibiotics reduced neratinib-induced diarrhea. This suggests that the microbiome may play a key role in the development and prolongation of diarrhea following neratinib treatment, although further research is required to understand the key bacteria and mechanisms by which they reduce diarrhea, as well as how this may impact presentation of diarrhea in clinical cohorts.


Combining laser therapies for optimal outcomes in treating the aging face and acne scars.
Aging and sun damage of the skin results in skin laxity, rhytides, texture irregularities, dyspigmentation, and vascular changes. Many different laser devices are frequently used to correct these changes from age and photodamage. This article describes the author's experience in combining laser technologies (different wavelengths and applications) in one treatment session to achieve better outcomes with fewer visits for the patient.


The nexus between CO2 emissions, human capital, technology transfer, and renewable energy: evidence from Belt and Road countries.
To sustain global warming below 2 °C, carbon dioxide emission mitigation has become an extensive worldwide priority. This paper proposes a comprehensive assessment by evaluating the effects of technology transfer, human capital, and renewable energy on carbon dioxide emissions among seven different regions along with the Belt and Road Initiatives from 2008 to 2018. Based on econometric estimations, it is found that human capital, renewable energy, and technology transfer show a negative but significant association with carbon dioxide emissions, indicating that an increase in human capital, renewable energy, and technology transfer can reduce carbon dioxide emissions in the Belt and Road countries. On the other hand, we found a positive and significant relationship between carbon dioxide emissions, economic growth, and foreign direct investment (FDI), indicating that economic growth and foreign direct investment increase carbon emissions. The findings of this study reveal that the adaptation of technology transfer, renewable energy consumption, and human capital are key factors in the reduction of carbon dioxide emissions in the Belt and Road counties. Our findings provide evidence of the social advantages of investing in advanced human capital, renewable energy, and technology transfer suggesting a promising route for devoting climate change without impeding economic growth.


Collagen binding site in collagenase can be determined using the concept of sense-antisense peptide interactions.
Tissue degradation and invasion are hallmarks of the metastatic phenotype. While several extracellular matrix components can be digested by proteases, degradation of interstitial collagen is selectively initiated by collagenase. It is obvious that inhibitors of collagenase activity would be extremely useful in preventing tissue destruction and tumor cell invasion and thus prove invaluable therapeutic agents. We describe here the possible development of such inhibitors through the use of the principle of complementary hydropathy. A peptide was deduced from the nucleotide sequence complementary to that coding for the region in interstitial collagen surrounding the bond between Gly775 and Ile776 which is cleaved by the enzyme. Labeled collagen binds specifically and quantitatively to this peptide. A polyclonal mouse serum raised against this peptide recognized purified human collagenase, was able to immunoprecipitate collagenase from cultured human keratinocyte supernatants and was effective in inhibiting collagenolytic activity with a K(iapp) = 0.3 microM.


Basal medium development for serum-free culture: a historical perspective.
The evolution of basal synthetic formulations to support mammalian cell culture applications has been facilitated by the contributions of many investigators. Definition of minimally-required nutrient categories by Harry Eagle in the 1950's spawned an iterative process of continuous modification and refinement of the exogenous environment to cultivate new cell types and to support emerging applications of cultured mammalian cells. Key historical elements are traced, leading to the development of high potency, basal nutrient formulations capable of sustaining serum-free proliferation and biological production. Emerging techniques for alimentation of fed batch and continuous perfusion bioreactors, using partial nutrient concentrates deduced from spent medium analysis, can enhance medium utilization and bioreactor productivity.


[Urological emergencies in two university hospitals in Douala: a retrospective study (2016-2020)].
urological emergencies are critical situations that require rapid response by a qualified urology health care professional. The purpose of this study was to highlight the profile of urological emergencies in two university hospitals in the city of Douala by assessing emergency management. we conducted a retrospective study of the urological emergencies in two reference hospitals in the city of Douala: the Laquintinie Hospital and the General Hospital. Files were collected over a period of 5 years (January 1st, 2016 to December 31st, 2020). All emergency consultations in the Emergency Unit as well as all clinical and therapeutic data from the on-call list during the study period were included. We excluded all emergencies (consultations during the study period) not recorded in the emergency registry. we conducted a study of 364 patients with an average age of 43 ± 8.34 years; 92.58% (n=337) of patients were male. The most common urological emergencies included: urinary retention (45.05%, n=164), renal colic (15.33%, n=56) and haematuria (13.18%, n=48). The most common cause of urinary retention was prostate tumors, renal colic was mainly due to renal lithiasis (96.45%, n=159) and hematuria was due to tumor in 68.75% (n=33) of patients. Therapeutic management was based on urinary catheterization (39.01%, n=142), medical treatment was associated with monitoring (27.47%, n=100) and suprapubic cystostomy (10.71%, n=39). acute urinary retention due to prostate tumors is the most common urological emergency in the university hospitals in the city of Douala. Early and optimal management of prostate tumors is therefore essential.


Post-Stroke Working Memory Dysfunction: A Meta-Analysis and Systematic Review.
This review investigates the severity and nature of post-stroke working memory deficits with reference to the multi-component model of working memory. We conducted a systematic search in PubMed up to March 2019 with search terms for stroke and memory. Studies on adult stroke patients, that included a control group, and assessed working memory function, were selected. Effect sizes (Hedges' g) were extracted from 50 studies (in total 3,084 stroke patients) based on the sample size, mean and standard deviation of patients and controls. Performance of stroke patients was compared to healthy controls on low-load (i.e. capacity) and high-load (executively demanding) working memory tasks, grouped by modality (verbal, non-verbal). A separate analysis compared patients in the sub-acute and the chronic stage. Longitudinal studies and effects of lesion location were systematically reviewed. Stroke patients demonstrated significant deficits in working memory with a moderate effect size for both low-load (Hedges' g = -.58 [-.82 to -.43]) and high-load (Hedges' g = -.59 [-.73 to -.45]) tasks. The effect sizes were comparable for verbal and non-verbal material. Systematically reviewing the literature showed that working memory deficits remain prominent in the chronic stage of stroke. Lesions in a widespread fronto-parietal network are associated with working memory deficits. Stroke patients show decrements of moderate magnitude in all subsystems of working memory. This review clearly demonstrates the global nature of the impairment in working memory post-stroke.


Non-alcoholic fatty liver disease: identical etiologic factors in patients with type 1 and type 2 diabetes.
To compare NAFLD prevalence, distribution and its etiologic determinants in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D). In this cross-sectional study, NAFLD was evaluated by transient elastography in adult outpatients with T1D and T2D. NAFLD was defined as hepatic steatosis with or without fibrosis. Associations between insulin resistance related factors and NAFLD and advanced fibrosis (≥ F3) were explored in T1D and T2D separately, using multivariate logistic regression models. Interaction analysis was performed to compare the associations in patients with T1D and T2D. One hundred and fifty patients with T1D (mean age 47 years, male 55%, mean diabetes duration 25 years, median BMI 25 kg/m2) and 100 patients with T2D (median age 67 years, male 56%, median diabetes duration 17 years, mean BMI 30 kg/m2) were included. NAFLD prevalence was 20% in patients with T1D and 76% in patients with T2D. Advanced fibrosis prevalence was 2.0% in patients with T1D and 22% in patients with T2D. In both patients with T1D and T2D, waist circumference, BMI and metabolic syndrome were positively associated, and estimated insulin sensitivity was negatively associated with the presence of NAFLD, adjusted for age, sex and diabetes duration. There was no effect modification by diabetes type for any of these associations. Despite differences in population characteristics and pathophysiology between T1D and T2D, insulin resistance related factors are similarly associated with NAFLD in both groups.


International intraocular lens registry.
To ensure the highest quality of care for patients, surgeons must have the most up-to-date information on the intraocular lenses (IOLs) they implant. This registry presents the lens constants (A constant, anterior chamber depth, and surgeon factor) for all commercially available IOLs--869 lenses from 22 manufacturers. The constants will be updated every January.


Acute abdominal aortic aneurysms: cost analysis of endovascular repair and open surgery in hemodynamically stable patients with 1-year follow-up.
To retrospectively assess the in-hospital and 1-year follow-up costs of endovascular aneurysm repair and conventional open surgery in patients with acute infrarenal abdominal aortic aneurysm (AAA) by using a resource-use approach. Institutional Review Board approval was obtained, and informed consent was waived. In-hospital costs for all consecutive patients (61 men, six women; mean age, 72.0 years) who underwent endovascular repair (n = 32) or open surgery (n = 35) for acute infrarenal AAA from January 1, 2001, to December 31, 2004, were assessed by using a resource-use approach. Patients who did not undergo computed tomography before the procedure were excluded from analysis. One-year follow-up costs were complete for 30 patients who underwent endovascular repair and for 34 patients who underwent open surgery. Costs were assessed from a health care perspective. Mean costs were calculated for each treatment group and were compared by using the Mann-Whitney U test (alpha = .05). The influence of clinical variables on the total in-hospital cost was investigated by using univariate and multivariate analyses. Costs were expressed in euros for the year 2003. Sex, age, and comorbidity did not differ between treatment groups (P > .05). The mean total in-hospital costs were lower for patients who underwent endovascular repair than for those who underwent open surgery (euro20 767 vs euro35 470, respectively; P = .004). The total costs, including those for 1-year follow-up, were euro23 588 for patients who underwent endovascular repair and euro36 448 for those who underwent open surgery (P = .05). The results of multivariate analysis indicated that complications had a significant influence on total in-hospital cost; patients who had complications incurred total in-hospital costs that were 2.27 times higher than those for patients who had no complications. Total in-hospital costs and total overall costs, which included 1-year follow-up costs, were lower in patients with acute AAA who underwent endovascular repair than in those who underwent open surgery.


Identification of alcoholics in the workplace.
Workplace programs make the supervisor responsible for identifying alcoholics through their job performance. However, research indicates that those so identified are a small proportion of the alcoholic employed population and tend to be in the later stages of the disease. This is due in part to the relatively small number of alcoholics who demonstrate performance deterioration in the early stages. In addition, only a few members of the drinking population are responsible for the costs to the organization resulting from poor job performance. The identification rate differs for alcoholics depending on their sex and level in the organization and the supervisory style of their managers. Hiding symptoms and cover-up for others adds to the proportion remaining unidentified. While identification through performance evaluation may be considered the only legitimate procedure in the workplace, it is not in fact identifying anywhere near the estimated number of alcoholics. The administrators and researchers in the employee assistance/occupational alcoholism field will have to decide whether to try innovative procedures that will broaden the scope of traditional programs. Such procedures may include cooperating with health promotion programs and identification through genetic and familial screening. While the current model identifies those most destructive to the organization, it bypasses a significant group of employees who are currently a danger to themselves or potentially a problem for the organization.


Knee Donor Site Morbidity Following Harvest of Medial Femoral Trochlea Osteochondral Flaps for Carpal Reconstruction.
This study examines donor site morbidity associated with the medial femoral trochlea (MFT) when used as a donor site for vascularized osteochondral flaps for reconstruction of challenging carpal defects such as proximal pole scaphoid nonunion and advanced Kienböck disease. The retrospective study population included all patients who had undergone MFT flap harvest for scaphoid or lunate reconstruction. Chart review, patient questionnaires, and validated knee function assessment tools were used: International Knee Documentation Committee Subjective Knee Form scores ranged from 0 (maximal disability) to 100 (no disability). Western Ontario and McMaster Universities osteoarthritis index scores ranged from 0% (no disability) to 100% (maximal disability). Magnetic resonance imaging and radiographs were obtained on the donor knee on the majority of patients. Questionnaire response rate was 79% (45 of 57 patients). Average patient age was 35 ± 11 years (range, 19-70 years). Average postoperative follow-up was 27 ± 17 months (range, 9-108 months). The indication for MFT flap reconstruction was scaphoid nonunion in 30 patients and Kienböck disease in 15 patients. All 45 patients had a stable knee on examination. Magnetic resonance and radiographic imaging obtained on 35 patients exhibited no pathological changes. Average duration of postoperative pain was 56 ± 59 days (range, 0-360 days); average duration until patients reported the knee returning to normal was 90 ± 60 days (range, 14-360 days). Forty-three of 44 patients would have the same surgery again if needed; overall satisfaction with the surgery was rated as 5 ± 1 (range, 2-5) on a scale from 0 (no satisfaction) to 5 (maximal satisfaction). Average International Knee Documentation Committee score was 96 ± 9 (range, 56.3-100) and the average Western Ontario and McMaster Universities score was 6% ± 16% (range, 0%-68%). Medial femoral trochlea osteochondral flap harvest results in minimal donor site morbidity in the majority of patients. Symptoms are time limited. Intermediate-term follow-up demonstrates excellent results in subjective outcome measures. Therapeutic IV.


Expression of occludin in human rectal carcinoid tumours as a possible marker for glandular differentiation.
To examine whether or not the tight junction-associated transmembrane protein occludin is expressed in rosette or gland-like structures in human rectal carcinoid tumours. The tight junction is crucial for the formation and maintenance of organized tubular structures in glandular epithelia. Previous studies have reported the presence of glandular structures in carcinoid tumours, though they are not believed to arise from glandular epithelium. The expression profiles of occludin in 40 carcinoid tumours were examined immunohistochemically, using an anti-occludin monoclonal antibody. In eight (20%) samples of typical carcinoid tumours, a small number of rosette-like tubular structures outlined by occludin were detected. Tight junction-associated molecules, including occludin, are thought to be one of the most characteristic structural markers of polarized glandular structures. The results of the present study provide supportive evidence that carcinoid tumour cells are capable of glandular differentiation.


Wide-band frequency-tunable terahertz and infrared detection with graphene.
We report a graphene-based frequency-selective terahertz (THz) and infrared (IR) detector. The experimental results have demonstrated that the graphene transistor under a magnetic field is capable of detecting THz and IR waves in a very wide band of frequencies (0.76-33 THz) and that the detection frequency is tuned by changing the magnetic field. We have further imaged electric potential distribution in the graphene detector and have observed local step structure associated with impurities. The THz and IR photoconductivity properties of graphene are likely to be sensitive to such potential steps.


Telomere shortening and telomerase expression during multistage carcinogenesis of intraductal papillary mucinous neoplasms of the pancreas.
Intraductal papillary mucinous neoplasm (IPMN) of the pancreas has been increasingly identified as a precursor to infiltrating ductal adenocarcinoma. Telomerase activation in response to telomere crisis followed by telomere shortening is thought to be a crucial event in the development of most human cancers. The aim of this study was to determine when this event occurs in the context of histologically defined IPMN progression. We analyzed telomerase expression in 68 IPMN samples and assessed telomere length by quantitative fluorescence in situ hybridization in samples taken from 17 sequential IPMN patients that included 37 individual loci. Samples from pancreatic ductal adenocarcinomas (PDACs, n=15) and chronic pancreatitis patients (n=10) were also examined. Telomeres were significantly shortened in 36 (97.3%) of 37 IPMN loci, with average telomere length decreasing with IPMN progression. Notably, even adenoma IPMNs demonstrated a 50% reduction of telomere length in 7 of 14 foci examined. Marked telomere shortening was observed from the in situ IPMN carcinoma stage (P<0.001; vs borderline IPMNs) through the invasive stage, although telomerase had been activated, indicating that telomeres had shortened to a critical length by this histological grade. Up-regulated human telomerase reverse transcriptase expression was detectable and increased gradually with cancer development and was primarily observed at the borderline IPMN stage and then in more advanced histopathologies. Progressive telomere shortening predominantly occurs during early IPMNs carcinogenesis before telomerase activation and progression from borderline to carcinoma in situ IPMNs is the critical stage of IPMNs carcinogenesis at which telomere dysfunction occurs.


A prospective evaluation of sexual function and quality of life after ileal pouch-anal anastomosis.
This study was designed to assess the effect of ileal pouch-anal anastomosis on sexual function and quality of life in men and women. Sexual function of patients undergoing ileal pouch-anal anastomosis from February 2005 to June 2006 was prospectively evaluated using the International Index of Erectile Function in men and Female Sexual Function Index in women. Quality of life was assessed using the Short Inflammatory Bowel Disease Questionnaire. Preoperative scores were compared with scores at 6 and 12 months postoperatively. Of 110 patients eligible for inclusion, 59 (53.6 percent) agreed to participate. Male sexual function and erectile function scores remained high 12 months after surgery (mean International Index of Erectile Function score 51.7 preoperative vs. 58.3 at 12 months postoperative; P = not significant (NS)). Abnormal sexual function decreased from 33.3 percent before surgery to 22.7 percent 12 months after surgery (P = NS). Female sexual function improved 12 months after surgery (mean Female Sexual Function Index score 19.2 preoperative vs. 27 at 12 months postoperative; P = 0.031). Abnormal sexual function decreased from 73.1 percent before surgery to 25 percent 12 months after surgery (P = 0.001). Quality of life significantly improved after ileal pouch-anal anastomosis in both sexes. In men, ileal pouch-anal anastomosis does not have an adverse effect on sexual function, whereas sexual function in women seems to improve 12 months after surgery.


Comparison of the cytotoxicity of two nitroheterocyclic drugs (NHCD) towards transformed and non-transformed cells.
The cytotoxicity of two nitroheterocyclic compounds (NHCD), Nitracrine, 1-nitro-9(3'3'-dimethylaminopropylamino) acridine (Polfa, Poland) and Quinifuryl, 2-(5'-nitro-2'-furanyl) ethenyl-4-[N-[4-(N,N-diethylamino)-1'-methylbutyl] carbamoyl] quinoline (Dr. N. M. Sukhova, Institute of Organic Synthesis, Riga, Latvian Republic), towards two lines of leukaemic cells and a line of non-transformed cells, was determined under normoxia conditions. Although both drugs showed significant cytotoxicity to all cell lines (LC(50) for 24h, < or = 2 microM) with that of Nitracrine exceeding Quinifuryl, their toxicity towards murine leukaemia P388 was substantially higher, compared to murine fibroblasts NIH3T3. In addition, the rate of cell death was also two- to three-fold higher in case of P388 cells versus NIH3T3. Interestingly, human erythroleukaemia K562 cells were shown to uptake the drugs 10 min after their addition to the tissue culture medium, while the LC(50) values were reached after a substantial delay of 3h. This delay might be due to the intracellular transformation of drugs required for cell killing.


Comparison of laparoscopic abdominal cerclage and transvaginal cerclage for the treatment of cervical insufficiency: a retrospective study.
To compare the pregnancy outcome of patients with cervical insufficiency (CI) underwent prophylactic laparoscopic abdominal cervical cerclage (LAC) and transvaginal cervical cerclage (TVC). A retrospective trial was carried out in the Department of Gynecology, Qingdao Women and Children's Hospital, Shandong Province, China. A total of 217 women with cervical insufficiency underwent the prophylactic cerclage, and the surgical approach was decided by the patients or depended on doctors' advice. The primary outcome measure was the fetal outcome. Secondary outcome measures were delivery of an infant at ≥ 34th gestational weeks, newborn birth weight, neonatal intensive care center (NICU) occupancy, and postoperative complications. Nonparametric variables were analyzed with the Mann-Whitney (U) test, and categorical type outcomes were analyzed with the Chi-square test or the Fisher's exact test. A P value < 0.05 was considered significant. Data analysis was performed using SPSS Statistics Version 19. As of follow-up date, 154 eligible patients were included in this study, with 74 (48.1%) women in the LAC group and 80 (51.9%) in the TVC group. The total fetal survival rate in the two groups was 90.3% (139/154), of which the rate significantly higher in the LAC group compared to the TVC group (97.3% vs. 83.8%, P < 0.01). The delivery of an infant at ≥ 34th gestational weeks was significantly higher in the LAC group compared to the TVC group (94.6% vs. 71.3%, P < 0.01). Compared to the TVC group, the mean newborn birth weight was higher, and the NICU occupancy rate was less in the LAC group (3293.4 ± 542.8 g vs. 2953.6 ± 704.4 g, P = 0.002; 2.8% vs. 17.9%, P = 0.003). No fatal surgical complications occurred in both groups. In patients with cervical insufficiency, the history-indicated conception of prophylactic LAC appears to have a better pregnancy outcome than TVC.


Immunity in mice vaccinated with a molecular weight 60,000 glycoprotein secreted by adult Nematospiroides dubius.
A mol. wt 60,000 glycoprotein was purified from adult Nematospiroides dubius excretory-secretory products (ES) by polyacrylamide gel electrophoresis and electroelution and used to vaccinate BCF1 mice. This molecule is also released from the surface of the parasite and can be cleaved by pepsin. Mice immunized twice with ES 60,000 in Alum adjuvant harboured similar numbers of N. dubius as did control mice but voided 40% fewer parasite eggs in their faeces. The mol. wt 60,000 component in ES and from the surface of the parasite appears to influence how the parasite reproduces and may be important to its survival.


Male nurse practice in inpatient rehabilitation. Finding a safe way: a grounded theory.
Research interest in nursing's contribution to inpatient rehabilitation is growing. Nurses contribute to rehabilitation specifically by teaching patients how to care for themselves. This contribution is largely reported from a female or genderneutral perspective. Despite the work of male nurses being examined in a range of other specialities, their work within inpatient rehabilitation remains underexplored. To report on a grounded theory study to identify and make visible male nurse practice in inpatient rehabilitation in Australia. Constructivist grounded theory informed by symbolic interactionism. Stage 1 data were collected in locations of participants choosing throughout Australia. Stage 2 data collection centred on seven data collection sites across two specialist rehabilitation hospitals in two states of Australia. Twenty-three male nurses and 15 patients participated in the study. Stage 1 (October 2013 to June 2014) consisted of semi-structured interviews with 11 male nurses. Stage 2 (February to April 2015) consisted of semi-structured interviews and 63.5 h of non-participant observation with 12 male nurses. Fifteen interviews with patients as recipients of male nurse care were also conducted. Data analysis included initial coding, focused coding, and theoretical coding using constant comparative methods, memo writing and diagramming. Nurse participants were aware of patient perceptions about nursing being an occupation for women and male nurses being perceived as sexual threats, which led to an everyday concern of potential for misinterpretation. To address this concern, male nurses engaged in a three-phase process known as assessing and managing risk in order to minimise risk and to keep themselves safe in practice. However, two contextual conditions, type of care and urgency of care, influenced engagement in assessing and managing risk. The core category and substantive grounded theory to explain these results is finding a safe way. Gender stereotypes affected the daily working lives of male nurses in inpatient rehabilitation. To counter the risk of misinterpretation male nurses used a range of strategies to address the barriers encountered daily in their working lives. However, male nurse efforts were often influenced by conditions outside of their control. In inpatient rehabilitation, male nurses practised cautiously to keep themselves safe in order to practise nursing.


Identification of the variants in PARL, the nuclear modifier gene, responsible for the expression of LHON patients in Thailand.
The present study explored variation in the PARL gene as one of the potential nuclear modifiers in the pathogenesis of Leber hereditary optic neuropathy (LHON). Ten exons, their franking introns and 3' UTR of the PARL gene were analysed. Seventeen SNPs detected were investigated in 83 affected and 53 unaffected individuals from 47 independent Thai LHON pedigrees using MQLS statistics in order to minimize the influence of the family background. Three intronic SNPs (rs953419, rs3749446 and rs1402000) showed statistically significant results. Joint haplotypes were constructed based on the genotypes at 3 SNPs and 7 possible haplotypes were observed in the 136 subjects. Our findings that the frequency of the haplotype AAC, and AAT were significantly higher in the unaffected cases and the frequencies of haplotype GGT were significantly higher in LHON cases, indicate that it might have a role in the penetrance of this mitochondrial disease.


Calcium carbonate treatment of diarrhoea in intestinal bypass patients.
To study the effect of supplemental calcium carbonate on faecal water, calcium, bile acid and lipid concentration and output in intestinal bypass subjects with diarrhoea. Prospective, single-arm treatment trial of oral calcium carbonate, 2400 or 3600 mg Ca2+ per day, given for 12 weeks. Faecal constituents were determined in wet or lyophilized stool of 24-h collections at baseline and at 12 weeks of study. Calcium was measured by absorption spectrophotometry. Bile acids, long-chain fatty acids and short-chain fatty acids were analysed by gas chromatography. In 15 subjects, calcium supplementation reduced bowel frequency by a mean of 49%, faecal wet weight by a mean of 50% (1292 to 646 g per day), and dry weight by a mean of 36%, P < 0.001. Faecal water concentration was reduced from 76.4 +/- 1% to 70.2 +/- 2%, P < 0.01. Faecal water concentration was inversely correlated with dry faecal calcium concentration (r = -0.75 P = 0.00001). Calcium reduces the diarrhoea of intestinal bypass patients. It is suggested that the constipating effect of calcium may be related to reduction in faecal water.


Industrial production of sourdoughs for the baking branch - An overview.
Sourdoughs are produced both in artisanal and industrial size. Sourdough manufacturers deliver the baking branch either with starters for production of in-house sourdoughs or with fully fermented sourdough products. In the latter case sourdough production is separated in time and space from the bread production. A big part of this convenience products are dried sourdoughs, which are mainly produced from rye and wheat flour, but also from other starch containing plants, like pseudocereals or legumes. The requirements regarding the raw materials used differ from that used for baking bread. The most applied drying techniques for sourdoughs are drum and spray-drying. Compared with other foods, sourdough and sourdough products have only a low risk regarding food safety due to pH < 4.2, however formation of biogenic amines or acrylamide has taken into account. More tools for sourdough authentication are needed but, before developing and validating methods, it would be necessary to include different sourdough products in a clear regulatory framework.


In silico characterization of competing endogenous RNA network in castration-resistant prostate cancer cells in presence of the natural compound atraric acid using RNA-seq analysis.
Atraric acid (AA) is a natural compound used for treatment of benign prostate hyperplasia. This agent has an anti-androgen receptor (AR) activity suppressing androgen-mediated neo-angiogenesis. In the current study, we have analyzed the transcriptome data of prostate cancer cells treated with AA (GSE172205) to find differentially expressed genes (DEGs) with an especial focus on lncRNAs and miRNAs. Then, we assessed expression of the differentially expressed lncRNAs (DElncRNAs) in available online sources to validate their association with prostate cancer and their importance in the determination of survival of patients with this type of cancer. We obtained 1871 DEGs, including 914 down-regulated DEGs (such as DAB1 and CD200) and 957 up-regulated DEGs (such as CHRNA2 and TRGC1), and 25 DElncRNAs, including 15 down-regulated DElncRNAs (such as LINC00639 and HOTTIP) and 10 up-regulated DElncRNAs (such as LINC00844 and LINC00160), and one up-regulated DEmiRNA (MIR29B1). The main pathways for the down-regulated genes and the up-regulated genes were Axon Guidance and Steroid BioSynthesis, respectively. Taken together, AA has been found to affect expression of several lncRNAs which are possibly involved in the pathoetiology of prostate cancer.


Exposure Classification and Temporal Variability in Urinary Bisphenol A Concentrations among Couples in Utah--The HOPE Study.
Bisphenol A (BPA) is an endocrine disruptor and potential reproductive toxicant, but results of epidemiologic studies have been mixed and have been criticized for inadequate exposure assessment that often relies on a single measurement. Our goal was to describe the distribution of BPA concentrations in serial urinary specimens, assess temporal variability, and provide estimates of exposure classification when randomly selected samples are used to predict average exposure. We collected and analyzed 2,614 urine specimens from 83 Utah couples beginning in 2012. Female participants collected daily first-morning urine specimens during one to two menstrual cycles and male partners collected specimens during the woman's fertile window for each cycle. We measured urinary BPA concentrations and calculated geometric means (GM) for each cycle, characterized the distribution of observed values and temporal variability using intraclass correlation coefficients, and performed surrogate category analyses to determine how well repeat samples could classify exposure. The GM urine BPA concentration was 2.78 ng/mL among males and 2.44 ng/mL among females. BPA had a high degree of variability among both males (ICC = 0.18; 95% CI: 0.11, 0.26) and females (ICC = 0.11; 95% CI: 0.08, 0.16). Based on our more stringent surrogate category analysis, to reach proportions ≥ 0.80 for sensitivity, specificity, and positive predictive value (PPV) among females, 6 and 10 repeat samples for the high and low tertiles, respectively, were required. For the medium tertile, specificity reached 0.87 with 10 repeat samples, but even with 11 samples, sensitivity and PPV did not exceed 0.36. Five repeat samples, among males, yielded sensitivity and PPV values ≥ 0.75 for the high and low tertiles, but, similar to females, classification for the medium tertile was less accurate. Repeated urinary specimens are required to characterize typical BPA exposure. Cox KJ, Porucznik CA, Anderson DJ, Brozek EM, Szczotka KM, Bailey NM, Wilkins DG, Stanford JB. 2016. Exposure classification and temporal variability in urinary bisphenol A concentrations among couples in Utah-the HOPE study. Environ Health Perspect 124:498-506; http://dx.doi.org/10.1289/ehp.1509752.


Development and validation of a purification system for functional full-length human SR-B1 and CD36.
Scavenger receptor class B type 1 (SR-B1) and CD36 are both members of the class B scavenger receptor family that play important roles in lipoprotein metabolism and atherosclerotic disease. SR-B1 is the primary receptor for high-density lipoproteins, while CD36 is the receptor responsible for the internalization of oxidized low-density lipoproteins. Despite their importance, class B scavenger receptor structure has only been studied by functional domain or peptide fragments-there are currently no reports of utilizing purified full-length protein. Here we report the successful expression and purification of full-length human SR-B1 and CD36 using an Spodoptera frugiperda insect cell system. We demonstrate that both SR-B1 and CD36 retained their normal functions in Spodoptera frugiperda cells, including lipoprotein binding, lipid transport, and the formation of higher order oligomers in the plasma membrane. Purification schemes for both scavenger receptors were optimized and their purity was confirmed by SDS-PAGE. Both purified scavenger receptors were assessed for stability by thermal shift assay and shown to maintain stable melting temperatures up to 6 weeks post-purification. Microscale thermophoresis was used to demonstrate that purified SR-B1 and CD36 were able to bind their native lipoprotein ligands. Further, there was no difference in affinity of SR-B1 for high-density lipoprotein or CD36 for oxidized low-density lipoprotein, when comparing glycosylated and deglycosylated receptors. These studies mark a significant step forward in creating physiologically relevant tools to study scavenger receptor function and lay the groundwork for future functional studies and determination of receptor structure.


Inhalative vaccination with pneumococcal polysaccharide in healthy volunteers.
In order to determine the feasibility of inhalative vaccination with polysaccharide antigen, we used controlled inhalation of a defined dose of Pneumovax in a randomized 3-arm study. The vaccine was either deposited in the alveoli (alveolar vaccination) or in the large airways (bronchial vaccination) and this was compared to standard intra-muscular vaccination. Adverse effects were minor and never exceeded WHO grade 2. There was frequent cough in the inhalative groups and frequent local pain at the injection site in the intra-muscular group. Specific serum IgG antibody measured before, and 4 and 12 weeks after, vaccination showed a greater than 2-fold rise in 4 out of 10 individuals after alveolar vaccination and in 6 out of 10 individuals after bronchial vaccination as compared to 10 out of 10 in the intra-muscular vaccination group. Average antibody levels of responders at 12 weeks were 350 microg/ml for alveolar vaccination, 200 microg/ml for bronchial vaccination and 1010 microg/ml for standard intra-muscular vaccination. Analysis of antibodies for 9 specific serotypes showed a more than 3-fold rise to 7-9 of the serotypes in the intra-muscular group. In both the bronchial and the alveolar group, all subjects responded but this was restricted to 2-4 of the 9 serotypes. The data show that polysaccharide vaccine can be safely administered by controlled inhalation and that it can induce good, albeit lower, serum antibody responses.


Patients that maintain their pre-injury level of physical activity 3-5 years after ACL reconstruction are, 18 months after surgery, characterised by higher levels of readiness to return to sport.
To characterise patients who had returned to their pre-injury physical activity (PA) or higher at 18 months and maintained that level of PA 3-5 years after the primary ACL reconstruction and to describe the level, frequency, and type of PA participation during the first 5 years after ACL reconstruction METHOD: Data, from follow-ups at 18 months and 3-5 years after an ACL reconstruction, were extracted from a rehabilitation-specific register. Patients, 15-65 years of age, were included. The data comprised patient-reported outcomes and the results from two questions with respect to the level, frequency, and type of PA. Comparisons were made between patients who had and had not maintained their pre-injury level of PA at the follow-up 3-5 years after an ACL reconstruction. A total of 272 patients met the inclusion criteria. The mean follow-up time was 3.8 years (min-max: 2.9-5.1) after the ACL reconstruction. Of patients who had returned to their pre-injury or a higher level of PA at the 18 month follow-up (n = 114), 68% (n = 78) maintained that level at the 3- to 5-year follow-up after ACL reconstruction. These patients reported a higher level of psychological readiness to return to sport (98 versus 79; p = 0.013). Moreover, these patients were 6.0 years older (p = 0.016) and were characterised by male sex (56% versus 44%; p = 0.028) and a lower level of pre-injury PA (p = 0.013). At the follow-up 3-5 years after the ACL reconstruction, more than 90% met the recommendations for PA. However, the prevalence of physical inactivity had increased and the involvement in organised PA had decreased compared with the 18-month follow-up. Two out of three patients who have returned to their previous level of PA at 18 months can be expected to maintain that level, 3-5 years following ACL reconstruction. These patients were mainly characterised by a higher level of psychological readiness, especially in patients who participated in knee-strenuous sport and were younger than 20 years of age. The results of this study suggest that patients become more physically inactive over time, implicating the importance of clinicians helping patients find a suitable PA that may help patients maintain an active lifestyle.


Synthesis and immunosuppressant activity of pyrazole carboxamides.
A series of novel pyrazole carboxamides is disclosed that demonstrate strong immunosuppressant activity in rodent and human mixed leukocyte response (MLR) assays (IC50 < 1 microM). The synthesis, biological activity, mode of action, and pharmacokinetic properties of this new lead series are discussed.


Room temperature hysteretic spin crossover in a new cyanoheterometallic framework.
A new iron(ii)-based spin-crossover compound with thermal hysteresis operating under ambient conditions is reported. This complex exhibits a high reproducibility of the spin transition in many successive thermal cycles, stability of both spin states at room temperature and an attractive operational temperature range.


Dynamic fluorescence in copper proteins. Selected examples.
The fluorescence properties of three copper proteins, namely human superoxide dismutase, Pseudomonas aeruginosa azurin and Thiobacillus versutus amicyanin have been studied. All these proteins show a non-exponential decay of fluorescence, though the tryptophanyl residues responsible for the emission are very differently located in the three proteins. All the three decays can be fitted by at least two lifetimes or better with one or two lorentzian-shaped, continuous distributions of lifetime. In each case the removal of copper affects the quantum yield of fluorescence without affecting the shape of the emission.


Oleuropein shows copper complexing properties and noxious effect on cultured SH-SY5Y neuroblastoma cells depending on cell copper content.
The secoiridoid oleuropein is a non-flavonoid polyphenol, found in the fruit, leaves and food derivatives from Olea europea. Like other polyphenols it shows a very low toxicity towards healthy tissues and a protective action against cancer or neurodegeneration, but its mechanism of action is not yet understood. In the present report we have used optical and ESR spectroscopy as well as molecular modelling to demonstrate that oleuropein forms a complex with the transition metal copper; the dysmetabolism of this metal is suspected to be involved in both cancer and neurodegeneration. Experiments carried out with the aglycon derivative of oleuropein, produced by β-glycosidase treatment of oleuropein glycoside, showed that also the aglycon forms copper-complexes, but with different spectroscopic features than the glycosidic form. Molecular modelling analysis confirmed that two oleuropein molecules (glycosidic or aglycon forms) can easily coordinate one copper ion. The relationship between oleuropein and copper was investigated in SH-SY5Y human neuroblastoma cells. When cells were depleted of copper by treatment with the copper chelator triethylenetetramine (Trien), that binds copper with higher affinity than oleuropein, oleuropein was less toxic than to copper-adequate cells. Conversely, incubation of SH-SY5Y cells with exogenous copper sulphate increased cell susceptibility to oleuropein. Furthermore SH-SY5Y cells differentiated by retinoic acid pre-treatment showed a lower level of copper, and were more resistant to oleuropein treatment. The oleuropein aglycon was not toxic towards SH-SY5Y cells. In conclusion, the copper-oleuropein complex may be involved in the toxicity of oleuropein towards tumour cells, depending on their copper level.


A Study of the Predictive Value of Treg and Th1/Th2 Cytokines on Pregnancy Outcome in Patients with Recurrent Pregnancy Loss.
To investigate the influence of helper T cell type 1 (Th1)/Th2 cytokines and Treg cells on the pregnancy outcome of patients with recurrent pregnancy loss (RPL) and to reveal the predictive value of their combination on the pregnancy outcome. The 165 RPL patients admitted to the Reproductive Medicine Department of the Second Hospital of Lanzhou University from September 2019 to June 2021 served as the research subjects for the study. The subjects comprised a live birth group (102 patients) or a non-live birth group (63 patients) based on their pregnancy outcomes. All patients were tracked through the end of pregnancy. Flow cytometry was applied to determine Treg and Th1/Th2 cytokine levels in the peripheral blood of patients without pregnancy. The levels of interleukin-6 (IL-6), IL-2, IL-10, and Treg in the RPL live birth group were significantly higher than those in the non-live birth group. The ratio of TNF - α/ IL-6, NF-α/ IL-10, IFN- γ/ IL-6, IFN- γ/ IL-10 in the non-live birth group increased significantly. The area under the curve (AUC) of Th1/Th2 cytokines combined with Treg cells was 0.786 (95% CI: 0.712-0.860), the specificity was 76.2%, and the sensitivity was 74.5%. Treg and Th1/Th2 cytokines showed a predictive ability for the pregnancy outcome of patients with recurrent pregnancy loss and their higher combined predictive efficacy. Meanwhile, in the Th1/Th2 immune response, its ratio was more important than the expression of a single cytokine.


[Surgical intensive care of the elderly].
Intensive care treatment of elderly patients is discussed controversially. Especially the success of maximal therapeutic efforts is questioned in this group. Therefore, this paper analyses prospective data of 1572 patients of a surgical intensive care unit with respect to age-related outcome. Besides the anticipated high proportion of concomitant diseases and an associated increased mortality of aged patients, there are no specific age-dependent differences. Old patients benefit from maximal therapeutic efforts to the same extent like younger patients. The authors conclude from the data that the patient's age per se should not influence the indication for intensive therapeutic interventions.


[Information interaction of the man-aircraft system as a problem in aviation medicine].
The importance of psychophysiological optimization of information interaction in the man--flying vehicle system is discussed having in view maintenance of good health and enhancement of efficiency and reliability of pilots. Several examples are presented that show the necessity of taking into consideration psychophysiological mechanisms, which regulate pilot's activities, in order to develop modified methods of information presentation and display.


The role and metabolic adaptations of neutrophils in premetastatic niches.
It has been found that tumor cells create microenvironments in distant organs that promote their survival and growth in advance of their arrival. These predetermined microenvironments are referred to as "pre-metastatic niches". Increasing attention is being paid to neutrophils' role in forming the pre-metastatic niche. As major components of the pre-metastatic niche, tumor-associated neutrophils (TANs) play an important role in the formation of the pre-metastatic niche through communication with multiple growth factors, chemokines, inflammatory factors, and other immune cells, which together create a pre-metastatic niche well suited for tumor cell seeding and growth. However, how TANs modulate their metabolism to survive and exert their functions in the process of metastasis remains largely to be discovered. Accordingly, the objective of this review is to assess the role that neutrophils play in the formation of pre-metastatic niche and to explore the metabolism alteration of neutrophils in cancer metastasis. A better understanding of the role of TANs in pre-metastatic niche will help us discover new mechanisms of metastasis and develop new therapies targeting TANs.


Major depressive disorder, personality disorders, and coping strategies are independent risk factors for lower quality of life in non-metastatic breast cancer patients.
Our aim was to identify risk factors for lower quality of life (QOL) in non-metastatic breast cancer patients. Our study included 120 patients from the University Hospital Centers of Tours and Poitiers. This cross-sectional study was conducted 7 months after patients' breast cancer diagnosis and assessed QOL (Quality of Life Questionnaire Core 30 = QLQ-C30), socio-demographic characteristics, coping strategies (Brief-COPE), physiological and biological variables (e.g., initial tumor severity and types of treatment received), the existence of major depressive disorder (Mini International Neuropsychiatric Interview), and pain severity (Questionnaire de Douleur Saint Antoine). We assessed personality disorders 3 months after diagnosis (Vragenlijst voor Kenmerken van de Persoonlijkheid questionnaire). We used multiple linear regression models to determine which factors were associated with physical, emotional, and global QOL. Lower physical QOL was associated with major depressive disorder, younger age, a more severe initial tumor stage, and the use of the behavioral disengagement coping. Lower emotional QOL was associated with major depressive disorder, the existence of a personality disorder, a more severe pain level, higher use of self-blame, and lower use of acceptance coping strategies. Lower global QOL was associated with major depressive disorder, the existence of a personality disorder, a more severe pain level, higher use of self-blame, lower use of positive reframing coping strategies, and an absence of hormone therapy. Lower QOL scores were more strongly associated with variables related to the individual's premorbid psychological characteristics and the manner in which this individual copes with the cancer (e.g., depression, personality, and coping) than to cancer-related variables (e.g., treatment types and cancer severity). Copyright © 2015 John Wiley & Sons, Ltd.


Functional asymmetry in the innervation of smooth muscle organs.
We studied functional asymmetry in the innervation of smooth muscle organs (right and left ureter, and right and left fallopian tubes). Asymmetry in the innervation of the right and left ureter is provided by activation of the purinergic system. Asymmetry in the innervation of the fallopian tubes is determined by the purinergic and serotoninergic mechanisms.


Course of pandemic influenza A(H1N1) 2009 virus infection in Dutch patients.
The clinical dynamics of influenza A(H1N1) 2009 infections in 61 laboratory-confirmed Dutch cases were examined. An episode lasted a median of 7·5 days of which 2 days included fever. Respiratory symptoms resolved slowly, while systemic symptoms peaked early in the episode and disappeared quickly. Severity of each symptom was rated highest in the first few days. Furthermore, diarrhoea was negatively associated with viral load, but not with faecal excretion of influenza virus. Cases with comorbidities appeared to have higher viral loads than the cases without, suggesting a less effective immune response. These results complement information obtained through traditional surveillance.


The F-actin filament capping protein CapG is a bona fide nucleolar protein.
Actin works in concert with myosin I to regulate the transcription of ribosomal genes in the nucleolus. Recently, nucleolar actin has been shown to be active in its polymeric form raising the question how actin dynamics is regulated in the nucleolus. Here, we show that the actin capping protein CapG localizes in the nucleolus of cultured cells. CapG transport to the nucleolus is an active and ATP-dependent process. Association of CapG with the nucleolus requires active RNA Polymerase I transcription. In addition, we show that activated Ran GTPase, an interaction partner of CapG, is also transported to the nucleolus. A constitutively active Ran mutant promotes CapG accumulation in the nucleolus indicating that CapG transport to the nucleolus can be supported by Ran. Our results suggest that filamentous actin in the nucleolus might be regulated by actin binding proteins such as CapG.


A Wood Biology Agenda to Support Global Vegetation Modelling.
Realistic forecasting of forest responses to climate change critically depends on key advancements in global vegetation modelling. Compared with traditional 'big-leaf' models that simulate forest stands, 'next-generation' vegetation models aim to track carbon-, light-, water-, and nutrient-limited growth of individual trees. Wood biology can play an important role in delivering the required knowledge at tissue-to-individual levels, at minute-to-century scales and for model parameterization and benchmarking. We propose a wood biology research agenda that contributes to filling six knowledge gaps: sink versus source limitation, drivers of intra-annual growth, drought impacts, functional wood traits, dynamic biomass allocation, and nutrient cycling. Executing this agenda will expedite model development and increase the ability of models to forecast global change impact on forest dynamics.


[Epidemiology and injury prevention in handball].
Handball is characterised by a high rate of injuries. Recent epidemiologic studies, which take the characteristics of handball into account, demonstrate a clear picture of injury patterns and injury risks for handball athletes. While more than half of all athletes can continue playing handball after medical treatment, the other half of injuries is accompanied by loss of training and match time. Although the sustained injuries are associated with a contact mechanism, they are not related to a high rate of foul play in the league setting. This shows that there is a high potential for prevention. Handball medicine strongly aims to primarily reduce and thus prevent injuries in this sport. The existing evidence for the potential of prevention of severe knee injuries must now be implemented into daily training. Due to the high prevalence of overuse injuries to the throwing shoulder, here, too, the first insights have been implemented in a prevention programme. This is described in detail in this article.


DJ-1 knock-down in astrocytes impairs astrocyte-mediated neuroprotection against rotenone.
Mutations that eliminate DJ-1 expression cause a familial form of Parkinson's disease (PD). In sporadic PD, and many other neurodegenerative diseases, reactive astrocytes over-express DJ-1 whereas neurons maintain its expression at non-disease levels. Since DJ-1 has neuroprotective properties, and since astrocytes are known to support and protect neurons, DJ-1 over-expression in reactive astrocytes may reflect an attempt by these cells to protect themselves and surrounding neurons against disease progression. We used neuron-astrocyte contact and non-contact co-cultures to show that DJ-1 knock-down in astrocytes impaired their neuroprotective capacity, relative to wild-type astrocytes, against the neurotoxin rotenone. Conversely, DJ-1 over-expression in astrocytes augmented their neuroprotective capacity. Experiments using astrocyte conditioned media on neuron-only cultures suggested that astrocyte-released, soluble factors were involved in the DJ-1-dependent, astrocyte-mediated neuroprotective mechanism. Our findings support the developing view that astrocytic dysfunction, in addition to neuronal dysfunction, may contribute to the progression of a variety of neurodegenerative disorders.


Mitochondrial dysfunction in progressive supranuclear palsy.
A progressive impairment of mitochondrial function has been suggested to play a critical role in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease and Huntington's disease. Mitochondrial dysfunction can lead to number of deleterious consequences including impaired calcium buffering, generation of free radicals, activation of the mitochondrial permeability transition pore and secondary excitotoxicity. Progressive supranuclear palsy (PSP) is a rare neurological disorder characterized by the appearance of supranuclear gaze palsy and extrapyramidal symptoms [Arch. Neurol. 10 (1964) 333]. Although the etiological basis of PSP is unknown, compelling evidence from spectroscopy studies in PSP patients, biochemical studies in post-mortem PSP brain tissue and PSP cybrids has emerged that supports a contributory role of bio-energetic defects in the pathogenesis of PSP.


Characterization of Viruses in Phase 3 and Phase 3b Trials (the Ring Study and the Dapivirine Ring Extended Access and Monitoring Trial) of the Dapivirine Vaginal Ring for Human Immunodeficiency Virus Type 1 Infection Risk Reduction.
The Ring Study demonstrated 35.1% human immunodeficiency virus type 1 (HIV-1) infection risk reduction among participants who used the Dapivirine vaginal ring-004 (DVR), whereas the Dapivirine Ring Extended Access and Monitoring (DREAM) trial, approximated a 62% risk reduction. The observed non-nucleoside reverse-transcriptase inhibitor (NNRTI) resistance-associated mutations (RAMs) and effects on viral susceptibility are described here. Population-based genotyping on plasma samples collected longitudinally, and next-generation sequencing (NGS) and phenotypic susceptibility testing were done on plasma collected at seroconversion. Retrospective HIV-1 RNA testing was used to more accurately establish the time of infection. In the Ring Study, NNRTI RAMs were not observed in most viruses at seroconversion (population-based genotyping: DVR: 71 of 84, 84.5%; placebo: 50 of 58, 86.2%). However, more E138A was found in the DVR group (E138A DVR: 9 of 84, 10.7%; placebo: 2 of 58, 3.4%; P = .2, Fisher exact test). NGS detected 1 additional mutation in each group (DVR: G190A; placebo: G190A and G190E). Marginal dapivirine susceptibility reduction was found with NNRTI RAMs at seroconversion (geometric mean fold-change, range: DVR, 3.1, 1.3-5.1; placebo, 5.8, 0.9-120). NNRTI RAMs were not emergent between first detectable HIV-1 RNA and seroconversion when these visits differed (paired samples, mean ring use: DVR, n = 52, 35 days; placebo, n = 26, 31 days). After stopping DVR, 2 of 63 viruses had emergent G190G/A or K103K/N with V106V/M at final study visit. Resistance profiles from the DREAM trial were consistent with the Ring Study. DVR showed little potential for selection of NNRTI-resistant variants. NCT01539226 and NCT02862171.


Recurrent trisomy 21: four cases in three generations.
Recurrent trisomy 21: four cases in three generations. While gonadal mosaicism can lead to recurrence of trisomy 21 (T21) for a single couple, the recurrence of free T21 in multiple members of a single pedigree has rarely been reported. We present an unusual pedigree with four cases of Down syndrome (DS) with free T21 were born to four separate women related through three generations of one family. The mothers were aged 18, 21, 29, and approximately 30 years at the time of the births. Using microsatellite markers, we excluded most of chromosome 21, excepting two small regions within 21q11.1 and 21q22.3, as being shared among the mothers of the DS children. However, two members of the pedigree, including one DS mother with a normal G-banded karyotype, carried supernumerary alleles at markers 2503J9TG, D21S369, and D21S215, which span the region from 21pter to 21q11.1. Fluorescence in situ hybridization using a centromeric probe hybridizing to chromosomes 13 and 21 did not reveal a novel location, ruling out a cryptic centromeric translocation between chromosome 21 and any chromosome other than chromosome 13. The level of meiotic recombination on chromosome 21 was unusually high in this family as well. We hypothesize that a cryptic rearrangement within the highly repetitive region of 21q11.1 is present in this family, disrupting pairing and leading to an increased risk of non-disjunction of chromosome 21 in this family.


NADPH oxidase-mediated generation of reactive oxygen species: A new mechanism for X-ray-induced HeLa cell death.
Oxidative damage is an important mechanism in X-ray-induced cell death. Radiolysis of water molecules is a source of reactive oxygen species (ROS) that contribute to X-ray-induced cell death. In this study, we showed by ROS detection and a cell survival assay that NADPH oxidase has a very important role in X-ray-induced cell death. Under X-ray irradiation, the upregulation of the expression of NADPH oxidase membrane subunit gp91(phox) was dose-dependent. Meanwhile, the cytoplasmic subunit p47(phox) was translocated to the cell membrane and localized with p22(phox) and gp91(phox) to form reactive NADPH oxidase. Our data suggest, for the first time, that NADPH oxidase-mediated generation of ROS is an important contributor to X-ray-induced cell death. This suggests a new target for combined gene transfer and radiotherapy.


Cryobaroenzymic studies as a tool for investigating activated complexes: creatine kinase.ADP.Mg.nitrate.creatine as a model.
By combining cryoenzymology with baroenzymology (a technique we term "cryobaroenzymology") one can obtain "stop-action" pictures of the intermediates in an enzyme reaction pathway and then observe their structural and energetic features ("motion features"). We illustrate the potential of this approach by considering the formation of a transient state analogue complex of creatine kinase (ATP:creatine N-phosphotransferase, EC 188.8.131.52): enzyme.ADP.nitrate.creatine, where nitrate mimics the transferable gamma-phosphate of ATP. Formation of the analogue complex is accompanied by a conformational change that manifests itself by tryptophan perturbation and thus allows kinetic studies by the stopped-flow method. We studied the formation of the analogue complex under cryoenzymic conditions as a function of pressure and solvent composition. This allowed a detailed description of the structural and energetic features of the activation process of an elementary step in an enzyme pathway.


Antagonism by morphine and pethidine of the contractile effects of PGE2 on isolated uterus of the rat.
Morphine antagonizes the twitches evoked by administration of PGE2 on spontaneous contractile activity in the isolated uterus of the rat. This action is dose-dependent. Concentrations as low as 2.6 nM completely abolished contractile activity of PGE2 added to the bath at a concentration of 0.5 ng ml-1. In contrast to morphine, pethidine partially antagonized the stimulatory action of PGE2 at much higher concentrations.


Comparisons between autistic and nonautistic children on the Test for Auditory Comprehension of Language.
Expressive language differences between autistic and nonautistic populations have been a topic of research in the past decade, yet little information is available in regard to the receptive language performances based on standardized tests. Questions as to the existence of sex differences in language have also been raised. The study examines the performance of 19 matched pairs of autistic and nonautistic children on the Test for Auditory Comprehension of Language. As well, the data were analyzed according to sex for each group. The results indicated that there were no significant differences between groups or between the sexes in either group. Questions for further research are raised.


Determination of trace amino acids in human serum by a selective and sensitive pre-column derivatization method using HPLC-FLD-MS/MS and derivatization optimization by response surface methodology.
Analysis of trace amino acids (AA) in physiological fluids has received more attention, because the analysis of these compounds could provide fundamental and important information for medical, biological, and clinical researches. More accurate method for the determination of those compounds is highly desirable and valuable. In the present study, we developed a selective and sensitive method for trace AA determination in biological samples using 2-[2-(7H-dibenzo [a,g]carbazol-7-yl)-ethoxy] ethyl chloroformate (DBCEC) as labeling reagent by HPLC-FLD-MS/MS. Response surface methodology (RSM) was first employed to optimize the derivatization reaction between DBCEC and AA. Compared with traditional single-factor design, RSM was capable of lessening laborious, time and reagents consumption. The complete derivatization can be achieved within 6.3 min at room temperature. In conjunction with a gradient elution, a baseline resolution of 20 AA containing acidic, neutral, and basic AA was achieved on a reversed-phase Hypersil BDS C(18) column. This method showed excellent reproducibility and correlation coefficient, and offered the exciting detection limits of 0.19-1.17 fmol/μL. The developed method was successfully applied to determinate AA in human serum. The sensitive and prognostic index of serum AA for liver diseases has also been discussed.


Spontaneous intracranial hypotension: the role of radiology in diagnosis and management.
Spontaneous intracranial hypotension (SIH) is a condition that results from leakage of cerebrospinal fluid (CSF) from the spine, and which typically presents with debilitating orthostatic headache, but can be associated with a wide range of other symptoms. The causes of spontaneous CSF leaks that lead to SIH include dural tears, leaking meningeal diverticula, and CSF-venous fistulas. Imaging plays a central role in the initial diagnosis of SIH and in its subsequent investigation and management. This article reviews the typical neuroimaging manifestations of SIH and discusses the utility of different myelographic techniques for localising spinal CSF leaks as well as the role of image-guided treatment.


A class II KNOX gene, KNOX4, controls seed physical dormancy.
Physical dormancy of seed is an adaptive trait that widely exists in higher plants. This kind of dormancy is caused by a water-impermeable layer that blocks water and oxygen from the surrounding environment and keeps embryos in a viable status for a long time. Most of the work on hardseededness has focused on morphological structure and phenolic content of seed coat. The molecular mechanism underlying physical dormancy remains largely elusive. By screening a large number of Tnt1 retrotransposon-tagged Medicago truncatula lines, we identified nondormant seed mutants from this model legume species. Unlike wild-type hard seeds exhibiting physical dormancy, the mature mutant seeds imbibed water quickly and germinated easily, without the need for scarification. Microscopic observations of cross sections showed that the mutant phenotype was caused by a dysfunctional palisade cuticle layer in the seed coat. Chemical analysis found differences in lipid monomer composition between the wild-type and mutant seed coats. Genetic and molecular analyses revealed that a class II KNOTTED-like homeobox (KNOXII) gene, KNOX4, was responsible for the loss of physical dormancy in the seeds of the mutants. Microarray and chromatin immunoprecipitation analyses identified CYP86A, a gene associated with cutin biosynthesis, as one of the downstream target genes of KNOX4 This study elucidated a novel molecular mechanism of physical dormancy and revealed a new role of class II KNOX genes. Furthermore, KNOX4-like genes exist widely in seed plants but are lacking in nonseed species, indicating that KNOX4 may have diverged from the other KNOXII genes during the evolution of seed plants.


Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease.
Idiopathic pulmonary fibrosis (IPF) is a fatal age-associated disease that is characterized by progressive and irreversible scarring of the lung. The pathogenesis of IPF is not completely understood and current therapies are limited to those that reduce the rate of functional decline in patients with mild-to-moderate disease. In this context, new therapeutic approaches that substantially improve the survival time and quality of life of these patients are urgently needed. Our incomplete understanding of the pathogenic mechanisms of IPF and the lack of appropriate experimental models that reproduce the key characteristics of the human disease are major challenges. As ageing is a major risk factor for IPF, age-related cell perturbations such as telomere attrition, senescence, epigenetic drift, stem cell exhaustion, loss of proteostasis and mitochondrial dysfunction are becoming targets of interest for IPF therapy. In this Review, we discuss current and emerging therapies for IPF, particularly those targeting age-related mechanisms, and discuss future therapeutic approaches.


Light-evoked cortical activity produced by illumination of intracranial retinal transplants: experimental studies in rats.
We have investigated whether information relayed through intracranial retinal transplants can elicit responses in the visual cortex of host rats. Embryonic retinae were transplanted over the midbrain of neonatal rats. Four to eight weeks later, the transplants were exposed and stimulated with light flashes. This photic stimulation elicited both evoked responses and multi-unit activity in area 18a of the visual cortex. Pathway tracing studies using horseradish peroxidase showed that these responses are transmitted to the cortex via the superior colliculus, the lateral division of the lateral posterior nucleus of the thalamus, and possibly the medial portion of the dorsal lateral geniculate nucleus. It is suggested that this pathway may be involved in complex transplant-mediated visual behaviors.


When pouring water on the fire makes it burn brighter.
Earlier work seems to suggest that overexpression of uncoupling protein 1 would be anti-inflammatory. However, new findings show that expression of uncoupling protein 1 in aortic smooth muscle cells of mice increases reactive oxygen species, activates the renin-angiotensin system, elevates blood pressure, and worsens atherosclerosis.


A role for inositol 1,4,5-trisphosphate in the initiation of agonist-induced contractions of dog tracheal smooth muscle.
To elucidate the role of inositol 1,4,5-trisphosphate (Ins-P3) in the initiation of agonist-induced contraction of the smooth muscle cells of the dog trachea, we investigated the effects of acetylcholine (ACh) on the concentrations of Ins-P3, phosphatidylinositol-4,5-bisphosphate (PI-P2) or phosphatidic acid (PA). The effects of Ins-P3 on the Ca2+ stored in the smooth muscle cells were also studied in saponin-permeabilized smooth muscle cells. A half maximal or maximal Ca2+ accumulation into the cells was observed in the dispersed single, smooth muscle cells treated by saponin, in free Ca2+ concentrations of 4.6 X 10(-7) or 5 X 10(-5)M, respectively. The ATP-dependent Ca2+ accumulation was maximal at 0.63 nmol/10(5) cells. Effects of Ins-P3 on stored Ca2+ were observed at a free Ca2+ concentration of 3.7 X 10(-7)M, which induces about half maximal ATP-dependent Ca2+-accumulation. Ins-P3 released the Ca2+ accumulated by ATP, in a dose-dependent manner. About 40% of the total Ca2+ was released following application of 3 microM Ins-P3. The release of stored Ca2+ induced by application of Ins-P3 was followed by its re-uptake into the smooth muscle cells. Thus, the stored Ca2+ was repeatedly released with repetitive applications of Ins-P3. Application of ACh (10(-5)M) to the dog trachea stimulated the production of Ins-P3 in the soluble fraction and 10s after this application, the relative amount of Ins-P3 was 290% of the control value. 6 Concomitantly, ACh (10- 5 M) either reduced or increased the contents ofphosphatidyl inositol 4,5-biphosphate (PI-P2) or phosphatidic acid (PA) in the lipid fraction ofthe smooth muscle cells to 60% or to 350% of the control value, respectively, thereby indicating that ACh stimulates the phosphodiesteric hydrolysis of PI-P2. 7 5-Hydroxytryptamine (5-HT; 10- 5M) also reduced or increased the contents of PI-P2 or PA to 80 or to 200% of the control values, respectively. However, neither histamine (10-5M), in the presence or absence of cimetidine (10-5M), nor prostaglandin F2 alpha. (PGF2 alpha. 1O-7 M) showed any effect on the contents of PI-P2 or PA in the lipid fraction of the smooth muscle cells. 8 These results indicate that in muscle cells of the dog trachea, Ins-P3 may play the role ofintracellular second messenger in the initiation of ACh or 5-HT-induced contraction, but not in the case of histamine or PGF2 alpha-induced contraction.


The α-lipoic acid improves high-fat diet-induced cerebral damage through inhibition of oxidative stress and inflammatory reaction.
This study is to clarify the protective role of α-lipoic acid in high-fat diet-induced cerebral damage mice. The mice were divided into 5 groups: normal control group, high-fat diet (HFD) group, low-dose α-lipoic acid group for prevention, high-dose α-lipoic acid group for prevention, and high-dose α-lipoic acid group for treatment. The groups' weights and blood glucose changes were monitored. We used HE staining to observe morphological changes in the cerebral cortex. The expression levels of the oxidative stress proteins SOD2, catalase, and the inflammatory pathway proteins p-JNK, p-ERK were measured by western blot and immunochemistry. Compared with the control group, the quantity of cortical neurons in the HFD group was decreased, and the samples exhibited retrogression. However, the lipoic acid significantly protected and promoted the cortical neurons survival. Moreover, compared with the HFD group, the expression levels of SOD2 and catalase in the three α-lipoic acid obtained groups were significantly increased. However, the expression levels of the inflammatory pathway proteins p-JNK and p-ERK were significantly decreased. These results indicate that theα-lipoic acid greatly protects the cortical neurons, and inhibited the oxidative stress and inflammatory reactions in the high-fat diet mice.


The statistical distribution of nucleic acid similarities.
All pairs of a large set of known vertebrate DNA sequences were searched by computer for most similar segments. Analysis of this data shows that the computed similarity scores are distributed proportionally to the logarithm of the product of the lengths of the sequences involved. This distribution is closely related to recent results of Erdos and others on the longest run of heads in coin tossing. A simple rule is derived for determination of statistical significance of the similarity scores and to assist in relating statistical and biological significance.


Mix-ups and mycoplasma: the enemies within.
Human leukemia-lymphoma (LL) cell lines represent important tools for experimental research. Among the various problems associated with cell lines, the two most common concern contaminations: (1) cross-contamination with unrelated cells and (2) contamination with microorganisms, in particular mycoplasma. The bad news is that about one-third of the cell lines are either cross-contaminated or mycoplasma-infected or both. The good news is that there are means to recognize and overcome these problems. In cases where, during attempts to establish new LL cell lines, primary LL cultures are cross-contaminated with continuous cell lines, intended new cell lines simply cannot be established ("early" cross-contamination). In cases of "late" cross-contamination of existing LL cell lines where the intrusive cells have a growth advantage, the original ("uncontaminated") cell lines may still be available elsewhere. DNA fingerprinting and cytogenetic analysis appear to be the most suitable approaches to detect cross-contaminations and to authenticate LL cell lines. A different but related aspect of "false" LL cell lines is the frequent misclassification of cell lines whereby the actual cell type of the cell line does not correspond to the purported model character of the cell line. Mycoplasma infection can have a multitude of effects on the eukaryotic cells which, due to the variety of infecting mycoplasma species and many other contributing parameters, cannot be predicted, rendering resulting data questionable at best. Practical procedures for the detection and elimination of mycoplasma contamination have been developed. Diagnostic and preventive strategies in order to hem the alarming increase in "false" and mycoplasma-positive LL cell lines are recommended.


The use of an ordinary colour scanner to fingerprint sediment sources in the South African Karoo.
The widespread adoption of sediment fingerprinting methodologies for the purpose of catchment management has been restricted by the high cost of tracer analysis as well as the potential for significant uncertainties to be present in results. Sediment colour has shown potential to be an inexpensive tracer able to discriminate between sediment sources. However, at present colour has not been demonstrated to be conservative during sediment erosion and transport. Sediment particle size and organic matter have been shown to strongly affect sediment colour, introducing significant uncertainties associated with its use. This study aimed to assess the suitability of colour as a tracer when it is measured using a commercially available colour scanner. The use of hydrogen peroxide (H2O2) to decompose sediment-associated organic matter was assessed as a means of minimising uncertainty. The impact of particle size on the accurate use of colour signatures as a tracer was also assessed. It was concluded that colour performed comparably to mineral magnetic signatures and showed good potential for use as a tracer. The use of H2O2 pre-treatment and limitation of the analysis to either the <32 μm or the >32 μm fraction of the samples were indicated to be important methods to limit uncertainties associated with organic matter and particle size. The methods used were considerably more time and cost effective than the measurement of most conventional tracers.


Thermal-crush injuries of the hands and forearms: an analysis of 60 cases.
The treatment of injuries inflicted on hands and occasionally forearms by crushing between hot rigid surfaces (thermal crush injury) is usually complex because of the possibility of fractures, nerve and tendon injuries, as well as heat destruction of the skin which also may be macerated. A review of the treatment of 60 patients with thermal crush injuries has defined the more important aspects of treatment including the choice of materials for wound coverage (split thickness skin or tube pedicle tissue graft) and the optimal time for surgical repair of the injury.


Demographic Comparison of Henosepilachna vigintioctopunctata (F.) (Coleoptera: Coccinellidae) Reared on Three Cultivars of Solanum melongena L. and a Wild Hostplant Solanum nigrum L.
Henosepilachna vigintioctopunctata (F.) is a widespread pest found on many solanaceous vegetables. The development and fecundity of H. vigintioctopunctata were studied on three cultivars ('Zihong', 'Eyou', and 'Baijiao') of eggplant, Solanum melongena L., using the two-sex life table theory. These results were then compared with similar parameters from a wild alternate host, Solanum nigrum. Our results showed that there were no significant differences between the developmental times of the larval stages, pupae, oviposition period, adult longevity, and the fecundity of H. vigintioctopunctata reared on the three eggplant cultivars. The survival rates of H. vigintioctopunctata larvae reared on the three eggplant cultivars were higher than that on S. nigrum. The fecundity of H. vigintioctopunctata adults reared on S. nigrum (724.12 eggs), however, was significantly higher than on each of the three eggplant cultivars. The values for the intrinsic rate of increase (r), finite rate of increase (λ), and net reproductive rate (R0) for H. vigintioctopunctata when reared on S. nigrum were 0.1225 d-1,1.1303 d-1, and 299.6 offspring, respectively. Each of these was significantly higher than comparable values when reared on the cultivar Eyou and Baijiao but were not different from those reared on the Zihong. Our results indicated that H. vigintioctopunctata is well adapted to all tested host plant cultivars and that S. nigrum is an important alternate wild hostplant that may potentially contribute to future outbreaks of H. vigintioctopunctata if not taken into consideration when planning an integrated control strategy against the pest.


Optimization of aqueous extraction of antioxidants from Chrysanthemum (C. morifolium Ramat and C. indicum L.) flowers and evaluation of their protection from glycoxidation damage on human αA-crystallin.
Chrysanthemum tea is commonly consumed by Chinese consumers mainly due to the Chrysanthemum flower being a potential source of antioxidants. The current study investigates the effects of extraction time and temperature on Chrysanthemum flower aqueous extract (CFAE) antioxidant capacity, including Trolox equivalent antioxidant capacity (TEAC), ferrous iron-chelating activity, and superoxide radical scavenging capacity (SRSC) using a two-factor, three-level factorial design of the response surface method (RSM). The TEAC and SRSC of CFAE are higher at higher temperatures and longer times up to a certain point, and the highest TEAC and SRSC are achieved at a 100 °C extraction temperature for 45 min. The fructose induced-αA-crystallin (Cry) glycation model system was used to evaluate the effects of the CFAE on anti-glycoxidation activities. The antioxidant ingredients obtained from CFAE significantly impede the production of advanced glycation end products from protein glycoxidation products (dityrosine, kynurenine, and N'-methylkynurenine) in the glycation process of αA-Cry and exhibit strong anti-glycating activity. The glycation inhibitory effects of CFAE are concentration-dependent. C. indicum L. exhibits greater potential for preventing cataracts compared to C. morifolium Ramat CFAE's antioxidant and anti-glycation properties suggest its potential application as a natural ingredient in the development of agents to combat glycation.


Identification of a restriction point at the M/G1 transition in CHO cells.
The regulation of cell cycle progression in normal mammalian cells is dependent on the presence of growth factors. In their absence, non-transformed cells will stop dividing and enter the quiescent state (G0). We show here that in Chinese hamster ovary cells, at least two serum-dependent points exist during G1 that lead to different cellular responses. The first point is located immediately after mitosis and is suggested to link with apoptosis. The second point is located late in G1, and probably corresponds with the 'classic' restriction point R. Cells depleted of serum after the first restriction point will not stop randomly in G1 but continue G1 progression until they reach the late restriction point, as marked by translocation of p42(MAPkinase) (ERK2) to the nucleus.


Effects of resistance exercise on blood glucose level and pregnancy outcome in patients with gestational diabetes mellitus: a randomized controlled trial.
To date, the effects of resistance exercise on diabetes-related parameters (blood glucose level and insulin use) and pregnancy outcome in participants with gestational diabetes mellitus (GDM) have not been compared with those of aerobic exercise. To investigate the effect of resistance exercise versus aerobic exercise on blood glucose level, insulin utilization rate, and pregnancy outcome in patients with GDM. From December 2019 to December 2020, 100 pregnant women with GDM were selected and divided into a resistance exercise group (49 patients) and an aerobic exercise group (51 patients) randomly. The aerobic exercise group received an aerobic exercise intervention, while the resistance exercise group received a resistance exercise intervention. Both groups received exercise intervention for 50-60 min, 3 times per week, lasting for 6 weeks. In addition, patients in both groups received the same routine care, including personalized dietary intervention, online education, and school courses for pregnant women. The blood glucose level in the resistance exercise group and the aerobic exercise group was lower after the intervention than before the intervention (p<0.05). After the intervention, no significant differences were observed in the fasting blood glucose level, insulin utilization rate, and incidence of adverse pregnancy outcomes between the two groups (p>0.05); however, significant differences were noted in 2-hour postprandial blood glucose level and exercise compliance between the two groups (p<0.05), with the resistance exercise group showing better outcomes than the aerobic exercise group. Resistance exercise is more compliant for pregnant women with GDM than aerobic exercise; hence, it is necessary to popularize resistance exercise in this specific population group. Long-term effects of resistance exercise should be evaluated in future studies. ChiCTR 1900027929.


Intraperitoneal infusion of 5-FU in liver metastases from colorectal cancer.
Intraperitoneal 5-fluorouracil (5-FU) was given to eight patients with unresectable colorectal liver cancer and to one patient after radical hepatectomy. A subcutaneous intraperitoneal access device was implanted, and treatment consisted of continuous infusion of 1,000 mg 5-FU/d for 5 days, repeated every 6 weeks. Evaluation of treatment was performed after every two cycles of therapy. A total of 32 infusion cycles were given. The mean steady-state concentration of 5-FU was 0.56 +/- 0.04 mumol/l (mean +/- SEM), and the total body clearance was 10.0 +/- 0.71/min mean +/- SEM). The levels of 5-FU in peripheral venous blood were stable and reproducible. When incubated in whole blood at 37 degrees C the concentration of 5-FU fell rapidly and after 2 h, only 22% of the starting level remained. When kept ice-cold, 5-FU samples were stable. Patient acceptance was excellent, and the therapy was free from complications except for slight abdominal discomfort, not enough to require alleviation by analgesic drugs. Computerized tomography (CT) scan showed stationary tumor volume after two cycles of therapy in four of eight patients who could be evaluated. It is concluded that continuous intraperitoneal infusion of 5-FU produces stable and reproducible levels of the drug in peripheral venous blood, that 5-FU is degraded by blood cells at 37 degrees C, that the use of a subcutaneous access device makes the delivery easy and safe, and that the efficacy of the therapy seems to be similar to that obtained with hepatic arterial infusion.


Perspective: Challenges and Future Directions in Clinical Research with Nuts and Berries.
Consumption of nuts and berries are considered part of a healthy eating pattern. Nuts and berries contain a complex nutrient profile consisting of essential vitamins and minerals, fiber, polyunsaturated fatty acids, and phenolics in quantities that improve physiological outcomes. The spectrum of health outcomes that may be impacted by the consumptions of nuts and berries includes cardiovascular, gut microbiome, and cognitive, among others. Recently, new insights regarding the bioactive compounds found in both nuts and berries have reinforced their role for use in precision nutrition efforts. However, challenges exist that can affect the generalizability of outcomes from clinical studies, including inconsistency in study designs, homogeneity of test populations, variability in test products and control foods, and assessing realistic portion sizes. Future research centered on precision nutrition and multi-omics technologies will yield new insights. These and other topics such as funding streams and perceived risk-of-bias were explored at an international nutrition conference focused on the role of nuts and berries in clinical nutrition. Successes, challenges, and future directions with these foods are presented here.


Oral absorption of bendazac lysine salt in man after repeated administrations.
The plasma levels of the lysine salt of bendazac were studied in man after repeated administrations. The substance was administered in 500 mg tablets three times daily for 21 days. Concentrations of bendazac ranging between 15 and 30 micrograms/ml were found in the plasma within 10 hours after the first administration. No significant differences were observed between the first and following days of treatment. Common laboratory and clinical tests did not show any marked change.


The guanidine thiocyanate-high EDTA method for total microbial RNA extraction from severely heavy metal-contaminated soils.
Molecular analyses relying on RNA, as a direct way to unravel active microbes and their functional genes, have received increasing attention from environmental researchers recently. However, extracting sufficient and high-quality total microbial RNA from seriously heavy metal-contaminated soils is still a challenge. In this study, the guanidine thiocyanate-high EDTA (GTHE) method was established and optimized for recovering high quantity and quality of RNA from long-term heavy metal-contaminated soils. Due to the low microbial biomass in the soils, we combined multiple strong denaturants and intense mechanical lysis to break cells for increasing RNA yields. To minimize RNAase and heavy metals interference on RNA integrity, the concentrations of guanidine thiocyanate and EDTA were increased from 0.5 to 0.625 ml g-1 soil and 10 to 100 mM, respectively. This optimized GTHE method was applied to seven severely contaminated soils, and the RNA recovery efficiencies were 2.80 ~ 59.41 μg g-1 soil. The total microbial RNA of non-Cr(VI) (NT) and Cr(VI)-treated (CT) samples was utilized for molecular analyses. The result of qRT-PCR demonstrated that the expressions of two tested genes, chrA and yieF, were respectively upregulated 4.12- and 62.43-fold after Cr(VI) treatment. The total microbial RNA extracted from NT and CT samples, respectively, reached to 26.70 μg and 30.75 μg, which were much higher than the required amount (5 μg) for metatranscriptomic library construction. Besides, ratios of mRNA read were more than 86%, which indicated the high-quality libraries constructed for metatranscriptomic analysis. In summary, the GTHE method is useful to study microbes of contaminated habitats.


Decisions and attitudes concerning child sexual abuse: does the gender of the perpetrator make a difference to child protection professionals?
An investigation was conducted into whether child protection investigators, specifically social workers and the police, are as likely to take seriously a case of child sexual abuse if it had been perpetrated by a female rather than a male. Also, to examine whether the decisions relating to female-perpetrated abuse were predicted by participants' sex role perceptions of women and their attitudes concerning women's sexualized behavior towards children. Participants advocated decisions in response to four hypothetical case of child sexual abuse in which the perpetrator was either male or female. The female perpetrators were then rated on femininity and masculinity characteristics and attitudes concerning women's sexualized behavior toward children were assessed. Following male--rather than female--perpetrated sexual abuse, case registration and imprisonment of the perpetrator was considered more appropriate by all participant groups; male social workers also considered social services involvement and investigation as more appropriate. A substantial number of decisions concerning female perpetrated abuse were predicted by participants' attitudes. While child protection professionals considered child sexual abuse perpetrated by females to be a serious issue warranting intervention, a number of advocated decisions suggested that they did not consider female-perpetrated abuse to be as serious as male-perpetrated abuse. The implication is that victims of sexual abuse perpetrated by a woman may be less likely to receive the protection afforded victims of male-perpetrated abuse. Furthermore, professionals' practices may be inadvertently perpetuating the view that female child sexual abuse is rare or less harmful than abuse carried out by males.


Changes in the endothelial morphology of the developing semilunar heart valves. A TEM and SEM study in the chick.
In view of recent evidence showing that shape and orientation of endothelial cells is determined by blood flow, the endothelium of the semilunar valves was studied in the developing chick heart using transmission and scanning electron microscopy. The results reveal significant developmental modifications of endothelial morphology and structure. These modifications can be linked to modifications of local blood flow and can also explain several aspects of valvular morphogenesis. The results substantially support the hypothesis of an involvement of hemodynamics in the development of the semilunar valves.