Increased soluble FcgammaRIIIa(Mphi) in plasma from patients with coronary artery diseases.
Atherosclerosis is the underlying disease process in patients affected with coronary artery diseases (CAD). Macrophages play a major role in the development of vascular lesions in atherogenesis. The cells express Fcgamma receptor type IIIa (FcgammaRIIIa: CD16) identical to that in natural killer cells (NK cells), but with a cell type-specific glycosylation. In contrast, neutrophils express FcgammaRIIIb. These FcgammaRIIIs are released from the cell surface on activation, and these soluble forms (sFcgammaRIII) are present in the plasma. We measured sFcgammaRIIIa(Mphi) in the plasma with a newly developed anti-FcgammaRIII mAb, MKGR14, which recognizes FcgammaRIIIa(Mphi) specifically. The level of sFcgammaRIIIa(Mphi), as well as the level of sFcgammaRIIIa (sFcgammaRIIIa(Mphi) plus sFcgammaRIIIa(NK)) or the level of total sFcgammaRIII (sFcgammaRIIIa plus sFcgammaRIIIb), were significantly increased in patients with CAD, but not in patients with vasospastic angina (VSA) or intact coronary arteries, compared with age-matched healthy donors. The sFcgammaRIIIa(Mphi) level was related to the number of significantly affected coronary arteries, and positively correlated with LDL-cholesterol to HDL-cholesterol ratios, but negatively with HDL-cholesterol. No correlation among the levels of three sFcgammaRIIIs was observed in CAD patients, as well as in healthy donors. The macrophages are activated during the process of atherosclerosis, and sFcgammaRIIIa(Mphi) may serve as a novel marker for atherosclerosis.


Principles of the well-managed community hospital.
Management of a community hospital must relate an exceptionally complicated organization to a dynamic and demanding environment. To do so requires a structure that guides decision processes. The author argues that five principles comprise this structure that is in place among today's successful hospitals. They are: (1) Success is measured by market shares at a satisfactory financial margin and an acceptable level of quality. (2) The business of a hospital is medical care, and doctors must be its allies. (3) Planning and budgeting decisions are the arena where trustees, executives, clinical professionals, and managers have their most frequent and meaningful collaboration. (4) Facts, and therefore information systems, are the key to successful planning and budgeting decisions. (5) Rewards are routine and generous to members of the hospital team who contribute to overall success.


A histochemical study of fibre types in rat extraocular muscles.
The histochemical fibre type composition of the rat superior and medial rectus (SR and MR), superior oblique (SO) and levator palpebrae superioris (LPS) muscles was studied using the myofibrillar ATPase and NADH-tetrazolium reductase (NADH-TR) techniques. In the SR, MR and SO a peripheral zone containing small fibres and a central zone containing both small and large fibres could be identified. Four fibre types were present in the central zone of these muscles and were categorised as Type 1, Type 2a. Type 2a'. and Type 2b. Four fibre types were also identified in the peripheral zone--Type 1, Type 2a, Type 2a' and Type 2c. In the LPS Type 1, Type 2, Type 2a', Type 2b and Type 2c fibres were evenly intermixed without a zonal arrangement. The Type 1, Type 2a, Type 2b and Type 2c fibres correspond to accepted fibres types in the rat limb muscles. The type 2a' and Type 2a" fibres were differentiated from the Type 2a fibres on the basis of size and pattern and intensity of staining with the NADH-TR technique. The Type 2c fibres, which possess both acid-stable and alkali-stable myofibrillar ATPase, are considered to represent intermediate fibres in the process of transformation from Type 2 to Type 1, rather than fibres with a dual innervation as has been suggested in the past. The implications of these histochemical findings are considered in relationship to the physiology of individual motor units and to the function of the extraocular muscles.


Rederivation of inbred strains of mice by means of embryo transfer.
Embryo transfers were performed to rederive six inbred strains of mice, A/He, BALB/cByJ, BALB/c Lac, B10.BR/SgSnJ, C57BL/6J and DBA/2J. The aim was to determine whether it is possible to eliminate pathogens like mouse hepatitis virus (MHV) and Pasteurella pneumotropica (P.p.). The embryos were collected, handled and transferred into the oviduct of day one pseudopregnant SPF surrogate mothers under aseptic conditions. In 40.5% of the transfers, embryos developed to term. With respect to surrogate mothers delivering viable litters, 47.9% of the transferred embryos were born alive. Out of these 93.5% were reared. Virological and bacteriological examination of embryo donors verified the presence of P.p. and of antibodies against MHV in all strains. In some embryo donors P.p. could be isolated even from the uterine mucosa. However, neither in the surrogate mothers nor in the offspring could P.p. and antibodies against MHV be detected. Further bacteriological examination revealed that the offspring carried only the microbial flora received from the surrogate mother. The results indicate that embryo transfer is an appropriate tool to rederive mouse strains. In contrast to hysterectomy rederivation, embryo transfer has the advantage of avoiding postimplantational vertical transmissions of infections.


The Impact of Nursing Staffs' Working Conditions on the Quality of Care Received by Older Adults in Long-Term Residential Care Facilities: A Systematic Review of Interventional and Observational Studies.
Little documentation exists on relationships between long-term residential care facilities (LTRCFs), staff working conditions and residents' quality of care (QoC). Supporting evidence is weak because most studies examining this employ cross-sectional designs. Systematic searches of twelve bibliographic databases sought experimental and longitudinal studies, published up to May 2021, focusing on LTRCF nursing staff's working conditions and the QoC they provided to older adults. Of the 3577 articles identified, 159 were read entirely, and 11 were retained for inclusion. Higher nursing staff hours worked per resident per day (HPRD) were associated with significant reductions in pressure sores and urinary tract infections. Overall staff qualification levels and numbers of RNs had significant positive influences on QoC. To the best of our knowledge, this systematic review is the first to combine cohort studies with a quasi-experimental study to explore associations between LTRCF nursing staff's working conditions and older adult residents' QoC. Human factors (including HPRD, staff turnover, skill mix, staff ratios) and the specific working contribution of RNs had overwhelmingly significant influences on QoC. It seems essential that LTRCF supervisory and decision-making bodies should promote optimal working conditions for nursing staff because these have such a direct impact on residents' QoC.


[Effect of aging on the sex distribution of depressive disorders].
The effects of age on sex differences in depression were studied in an inpatient-sample of the Department of Psychiatry, Free University Berlin. The dependent variable depression was defined by nosological classification (ICD) and by the severity of the Depressive Syndrome of the AMP-Rating Scale on admission. With the exception of the 40-49 years olds women were more often diagnosed as depression compared to men, the preponderance of women was significant till the age of 40. With regard to the Depressive Syndrome women manifested a more pronounced symptomatology up to the age of 70. The difference diminished for male and female patients 50-69 years old and changed to a higher score for men older than 70. The results were discussed in comparison to other findings published in the last years.


Risk factors for inguinal hernia in women: a case-control study. The Coala Trial Group.
Potential risk factors for inguinal hernia in women were investigated and the relative importance of these factors was quantified. In women, symptomatic but nonpalpable hernias often remain undiagnosed. However, knowledge on this subject only concerns hernia and operation characteristics, which have been obtained by review of case series. Virtually nothing is known about risk factors for inguinal hernia. The authors performed a hospital-based case-control study of 89 female patients with an incident inguinal hernia and 176 age-matched female controls. Activity since birth with two validated questionnaires was measured and smoking habits, medical and operation history, Quetelet index (kg/m2), and history of pregnancies and deliveries were recorded. Response for cases was 81% and for controls 73%. Total physical activity was not associated with inguinal hernia (univariate odds ratio (OR) = 0.8, 95% confidence interval (CI) 0.6-1.1), but high present sports activities was associated with less inguinal hernia (multivariate OR = 0.2, 95% CI 0.1-0.7). Obesity (Quetelet index > 30) was also protective for inguinal hernia (OR = 0.2, 95% CI 0.04-1.0). Independent risk factors were positive family history (OR = 4.3, 95% CI 1.9-9.7) and obstipation (OR = 2.5, 95% CI 1.0-6.7). In particular, smoking, appendectomy, other abdominal operations, and multiple deliveries were not associated with inguinal hernia in females. The protective effect of present sports activity may be explained by optimizing the resistance of the abdominal musculature protecting the relatively small inguinal weak spot in the female. The individual predisposition for inguinal hernia may be quantified by these risk factors, and, with this in mind, the authors advise that further evaluation might be needed for the patient with unexplained inguinal pain.


Present status and future vision of the International Medical Co-operation for Leprosy.
In the year 2002, leprosy situation in Thailand has been steadily progress. However, the prevalence rate and percentage of leprosy patients are still quite high in the North-Eastern part of Thailand. Therefore, we have focused our plan of action 2001-2 on "The strengthening of Leprosy Elimination and Prevention of Disability in the North-Eastern Region." The objective of which is to improve and sustain the ability of leprosy related staff to conduct activities such as case finding, complication diagnosis, treatment of disabilities, rehabilitation, supervision and evaluation. The International Medical Co-operation for Leprosy in 2001, we received funds from Netherland Leprosy Relief Association (NLR) for 9 programmes concerning training of leprosy for health officers and assessment of the quality of life for leprosy affected persons living in northeastern colonies. There are 3 training courses of leprosy for new medical doctors, lab technicians from community and provincial hospitals and 2 workshops on Rehabilitation and Development of Leprosy Affected Persons "Quality of Life" under the Germany Leprosy Relief Association (GLRA) support. From Japan we received funding from Sasakawa Memorial Health Foundation (SMHF) for 4 projects in immunological studies since 1997 and 2 projects concerning dental services for Leprosy patients in the north and northeast regions from Umemoto Memorial Dental Service Group (UMDSG). The medical co-operation between Japan and Thailand should increase in many aspects especially, for new chemotherapy, immunotherapy and vaccine study in Leprosy. The future vision of Leprosy, we plan to set up the International Center of Leprosy for medical officers, technicians, etc. for the South-East Asian Countries. You are welcome to join and work together with us.


Interns' evaluation of their preparation for general practice: a comparison between the University of Tromsø and the University of Bergen.
A total of 168 interns who have graduated from the Medical Schools of Bergen and Tromsø were asked about various aspects of the medical curriculum. In Bergen the curriculum has a traditional structure with a pre-clinical and a clinical part, but in Tromsø the pre-clinical and clinical subjects are integrated. In addition, the students in Tromsø spend long periods in municipal hospitals and in the primary health care service. We were interested in how the interns from the two universities evaluated their respective curricula and how prepared they felt for their current work. There was a response rate of 86% to the questionnaire. The results showed that the interns from Tromsø are more satisfied with their education and feel more confident in their practical skills than the interns from Bergen. They are also more motivated for future work in general practice. In our opinion the main reason for these results is the difference in curricula in the two medical schools. Other possible reasons are also discussed.


Transforming growth factor-beta1 modulates p107 function in myeloid cells: correlation with cell cycle progression.
Transforming growth factor-beta1 (TGF-beta1) is a potent inhibitor of hematopoietic cell growth. Here we report that TGF-beta1 signals inhibition of IL-3-dependent 32D-123 murine myeloid cell growth by modulating the activities of cyclin E and cyclin-dependent kinase 2 (cdk2) proteins and their complex formation in the G1 phase of the cell cycle. Whereas the cyclin E protein was hyperphosphorylated in TGF-beta1 treated cells, TGF-beta1 decreased both the phosphorylation of cdk2 and the kinase activity of the cyclin E-cdk2 complex. Decreased cyclin E-cdk2 kinase activity correlated with decreased phosphorylation of the retinoblastoma-related protein p107. In support of these observations, transient overexpression of p107 inhibited the proliferation of the myeloid cells, and expression of antisense oligodeoxynucleotides to p107 mRNA blocked TGF-beta1 inhibition of myeloid cell growth. Furthermore, as reported previously, in 32D-123 TGF-beta1 treated cells, c-Myc protein expression was decreased. TGF-beta1 increased the binding of p107 to the transcription factor E2F, leading to decreased c-Myc protein levels. p107 inhibited E2F transactivation activity and was also found to bind the c-Myc protein, suggesting p107 negative regulation of c-Myc protein function. These studies demonstrate the modulation of p107 function by TGF-beta1 and suggest a novel mechanism by which TGF-beta1 blocks cell cycle progression in myeloid cells.


Protonated alcohols are examples of complete charge-shift bonds.
Accurate gas-phase and solution-phase valence bond calculations reveal that protonation of the hydroxyl group of aliphatic alcohols transforms the C-O bond from a principally covalent bond to a complete charge-shift bond with principally "no-bond" character. All bonding in this charge-shift bond is due to resonance between covalent and ionic structures, which is a different bonding mechanism from that of traditional covalent bonds. Until now, charge-shift bonds have been previously identified in inorganic compounds or in exotic organic compounds. This work showcases that charge-shift bonds can occur in common organic species.


O-Protected NH-free hydroxylamines: emerging electrophilic aminating reagents for organic synthesis.
In this highlight, O-protected NH-free hydroxylamine derivatives have been evaluated in the construction of nitrogen-enriched compounds, such as primary amines, amides, and N-heterocycles, with high regio-, chemo- and stereoselectivity in the unprotected form, showcasing the late-stage functionalization of natural products, drugs and functional molecules by biocatalysis, organocatalysis, and transition metal catalysis. The reactivity dichotomy among these N-O reagents has been explored based on SET and metal-nitrenoids.


Estimating individual glomerular volume in the human kidney: clinical perspectives.
Measurement of individual glomerular volumes (IGV) has allowed the identification of drivers of glomerular hypertrophy in subjects without overt renal pathology. This study aims to highlight the relevance of IGV measurements with possible clinical implications and determine how many profiles must be measured in order to achieve stable size distribution estimates. We re-analysed 2250 IGV estimates obtained using the disector/Cavalieri method in 41 African and 34 Caucasian Americans. Pooled IGV analysis of mean and variance was conducted. Monte-Carlo (Jackknife) simulations determined the effect of the number of sampled glomeruli on mean IGV. Lin's concordance coefficient (R(C)), coefficient of variation (CV) and coefficient of error (CE) measured reliability. IGV mean and variance increased with overweight and hypertensive status. Superficial glomeruli were significantly smaller than juxtamedullary glomeruli in all subjects (P < 0.01), by race (P < 0.05) and in obese individuals (P < 0.01). Subjects with multiple chronic kidney disease (CKD) comorbidities showed significant increases in IGV mean and variability. Overall, mean IGV was particularly reliable with nine or more sampled glomeruli (R(C) > 0.95, <5% difference in CV and CE). These observations were not affected by a reduced sample size and did not disrupt the inverse linear correlation between mean IGV and estimated total glomerular number. Multiple comorbidities for CKD are associated with increased IGV mean and variance within subjects, including overweight, obesity and hypertension. Zonal selection and the number of sampled glomeruli do not represent drawbacks for future longitudinal biopsy-based studies of glomerular size and distribution.


Evaluation of the role of peroxisome-proliferator-activated receptor alpha in the regulation of cardiac pyruvate dehydrogenase kinase 4 protein expression in response to starvation, high-fat feeding and hyperthyroidism.
Inactivation of cardiac pyruvate dehydrogenase complex (PDC) after prolonged starvation and in response to hyperthyroidism is associated with enhanced protein expression of pyruvate dehydrogenase kinase (PDK) isoform 4. The present study examined the potential role of peroxisome-proliferator-activated receptor alpha (PPARalpha) in adaptive modification of cardiac PDK4 protein expression after starvation and in hyperthyroidism. PDK4 protein expression was analysed by immunoblotting in homogenates of hearts from fed or 48 h-starved rats, rats rendered hyperthyroid by subcutaneous injection of tri-iodothyronine and a subgroup of euthyroid rats maintained on a high-fat/low-carbohydrate diet, with or without treatment with the PPARalpha agonist WY14,643. In addition, PDK4 protein expression was analysed in hearts from fed, 24 h-starved or 6 h-refed wild-type or PPARalpha-null mice. PPARalpha activation by WY14,643 in vivo over the timescale of the response to starvation failed to up-regulate cardiac PDK4 protein expression in rats maintained on standard diet (WY14,643, 1.1-fold increase; starvation, 1.8-fold increase) or influence the cardiac PDK4 response to starvation. By contrast, PPARalpha activation by WY14,643 in vivo significantly enhanced cardiac PDK4 protein expression in rats maintained on a high-fat diet, which itself increased cardiac PDK4 protein expression. PPARalpha deficiency did not abolish up-regulation of cardiac PDK4 protein expression in response to starvation (2.9-fold increases in both wild-type and PPARalpha-null mice). Starvation and hyperthyroidism exerted additive effects on cardiac PDK4 protein expression, but PPARalpha activation by WY14,643 did not influence the response of cardiac PDK4 protein expression to hyperthyroidism in either the fed or starved state. Our data support the hypothesis that cardiac PDK4 protein expression is regulated, at least in part, by a fatty acid-dependent, PPARalpha-independent mechanism and strongly implicate a fall in insulin in either initiating or facilitating the response of cardiac PDK4 protein expression to starvation.


Avoiding the trauma of organizational downsizing.
Downsizing an organization as a means to reduce costs can often lead to a disruptive hospital environment and traumatic experiences for employees, especially when reducing staff. By taking a planned and systematic approach, hospitals can make staff reductions a less painful experience. Through better communications, sound reasoning, good organizational analyses, and understanding, hospitals and employees alike can better survive the trauma of the downsizing experience.


Establishment of odontoblastic cells, which indicate odontoblast features both in vivo and in vitro.
Tooth tissue engineering offers very attractive perspectives for elaboration of regenerative treatments, which enables to cure tooth loss and restore quality of life of the patients. To elaborate such treatment, isolation and culture of dental pulp cell must be achieved as a key element. In this article, we report the establishment of a stable cell line from GFP transgenic rat dental pulp, named TGC (Tooth Matrix-forming, GFP Rat-derived Cell). TGCs have exhibited odontoblastic feature both in vitro and in vivo. In vitro, TGC exposed to osteogenic medium demonstrated collagen fiber synthesis with matrix vesicle and mineralization and formed a sheet-like substrate on the cell culture dish. Increased ALP activity and elevated transcription level of various genes involved in calcification and dentin formation were also observed. In vivo, transplanted TGC in SCID mice with β-TCP particles formed dentin-like and pulp-like structure with lining odontoblast. Notably, even after up to 80 passages, TGCs retain their morphological features and differentiation ability. To our knowledge, this is the first report of a dental pulp-derived cell with such stable odontoblastic characteristics. TGC could be a very useful model for further study on dental pulp cell.


APOE gene polymorphism analysis in Barranquilla, Colombia.
The genetic variability present in the APOE gene polymorphism is considered an important factor associated with predisposition to diseases affecting lipid metabolism, as well as heart diseases and Alzheimer's disease, among others. Understanding it as a risk factor in different populations and ethnic groups is a useful tool. To analyze the APOE gene polymorphism and determine allelic and genotypic frequencies of a representative sample of population from Barranquilla, Colombia. We performed a descriptive and comparative study. The sample size was 227 unrelated individuals from Barranquilla, Colombia. The most frequent allele was the ε3, with 85%, followed by the ε4 allele (13%) and ε2 (1.8%). The genotypes found were: ε3/ε3: 71.8%, ε3/ε4: 24.2%, ε2/ε3: 2.2%, ε2/ε4: 1.3% and ε4/ε4: 0.4%. The ε2/ε2 genotype was not found in this study. The sample exhibited the Hardy-Weinberg equilibrium. The frequency of the ε3 allele and the ε3/ε3 genotype was similar to that reported in the literature in countries like Brazil, Mexico, Colombia, and in some Colombian Amerindian ethnic groups. The ε2/ε2 genotype was absent. This result is consistent with those found in other population groups worldwide. The frequency of the ε4 allele and the genotypes associated in this population could be related to the presence of diseases such as hypercholesterolemia, myocardial infarction and Alzheimer.


Association analysis identifies TLR7 and TLR8 as novel risk genes in asthma and related disorders.
Toll-like receptors (TLRs) are structurally and functionally related and play important roles in the innate and adaptive immune system. By genome scanning, evidence of linkage between chromosome Xp22 and asthma and related atopic disorders has previously been obtained. Xp22 harbours the TLR7 and TLR8 genes. The involvement of TLR7 and TLR8 in the aetiology of asthma and related disorders was investigated by a family based association analysis of two independently ascertained family samples comprising 540 and 424 individuals from 135 and 100 families, respectively. Ten affected individuals from families showing evidence of linkage to Xp22 were screened for sequence variations in TLR7 and 8, and nine single nucleotide polymorphisms (SNPs) identified were tested for association. In both samples, significant associations were observed for single SNPs and haplotypes of both TLR7 and 8 in all four phenotypes investigated: asthma, rhinitis, atopic dermatitis and increased specific IgE. The most significant association was seen for rs2407992 (TLR8) in asthma (p = 0.00023, sample A and B combined, recessive model). In TLR7, rs179008 showed the strongest association. Both rs179008 and rs2407992 are of putative functional significance, potentially affecting TLR7 processing and TLR8 splicing, respectively. Haplotypes comprising the major alleles of these two SNPs were overtransmitted to the affected offspring (eg, p = 0.00012 in asthma, combined sample, additive model). The results provide strong evidence that TLR7 and 8 may confer susceptibility to asthma and related atopic disorders and highlight these receptors as interesting targets for individualised, causally directed treatment.


Adherence to treatment: assessment of an unmet need in asthma.
In asthma, as in other chronic conditions, poor adherence to treatment and to medical advice is common and contributes to substantial worsening of the disease and increased health care costs. The aim of the present study was to evaluate patients' self-reported adherence to asthma medication regimens and to identify possible correlations between treatment adherence and depression, anxiety, and coping strategies. Sixty-three asthmatic outpatients (27 men and 36 women; mean age +/- SD, 38.5 +/- 14.1) were consecutively enrolled during their routine control visit. Patients were asked to complete 3 different questionnaires: the Adherence Schedule in Asthma, the Hospital Anxiety and Depression Scale, and the Coping Orientations to Problem Experienced questionnaires. Depression was detected in 32.3% of patients and anxiety in 34.9%. A negative correlation was found between older age and perception of family support (rho = -0.33). The presence of anxiety displayed a positive correlation with difficulty in accepting the illness (rho = 0.33) and a negative correlation with acceptance of illness limitations (p = -0.30); it was also positively correlated with fear of the side effects of medication (rho = 0.37). The presence of depression was negatively correlated with acceptance of illness limitations (rho = -0.32), knowledge of the illness (p = -0.29), and with ability to identify worsening signs (rho = -0.31). This study shows how different factors may modulate adherence to asthma treatment. The opportunity to identify reasons for nonadherence through a simple assessment will allow a tailored intervention to be planned for each patient.


Single base substitutions in the capsid region of the norovirus genome during viral shedding in cases of infection in areas where norovirus infection is endemic.
Norovirus (NoV) infections are the major cause of food- and waterborne nonbacterial gastroenteritis in Japan. Some individuals showed long-term excretion of the virus into feces in 29 outbreaks of acute nonbacterial gastroenteritis that occurred in Toyama Prefecture, Japan, in fiscal year 2006. In one of these cases, single base substitutions from A to G in the capsid region of the NoV genome were commonly detected in two individuals during virus shedding by direct sequencing of PCR products. The A-to-G substitution was accompanied by an N-to-S amino acid change. The population of clones that possessed A at the corresponding site was gradually replaced by those with G during the infectious course. Although other substitutions were observed in the complete open reading frame 2 sequence, they were not common in these two individuals. NoVs are capable of evolving in the gastroenteric tract.


Genetic Restoration of Heme Oxygenase-1 Expression Protects from Type 1 Diabetes in NOD Mice.
Antigen-presenting cells (APCs) including dendritic cells (DCs) play a critical role in the development of autoimmune diseases by presenting self-antigen to T-cells. Different signals modulate the ability of APCs to activate or tolerize autoreactive T-cells. Since the expression of heme oxygenase-1 (HO-1) by APCs has been associated with the tolerization of autoreactive T-cells, we hypothesized that HO-1 expression might be altered in APCs from autoimmune-prone non-obese diabetic (NOD) mice. We found that, compared to control mice, NOD mice exhibited a lower percentage of HO-1-expressing cells among the splenic DCs, suggesting an impairment of their tolerogenic functions. To investigate whether restored expression of HO-1 in APCs could alter the development of diabetes in NOD mice, we generated a transgenic mouse strain in which HO-1 expression can be specifically induced in DCs using a tetracycline-controlled transcriptional activation system. Mice in which HO-1 expression was induced in DCs exhibited a lower Type 1 Diabetes (T1D) incidence and a reduced insulitis compared to non-induced mice. Upregulation of HO-1 in DCs also prevented further increase of glycemia in recently diabetic NOD mice. Altogether, our data demonstrated the potential of induction of HO-1 expression in DCs as a preventative treatment, and potential as a curative approach for T1D.


Avascular femoral head necrosis in pediatric cancer patients.
Avascular femoral head necrosis was identified in 15 patients treated at a major pediatric oncology center from 1974 to 1991. The predominant underlying diagnosis was acute leukemia (lymphoblastic, n = 6; non-lymphoblastic, n = 2); two patients had chronic myeloid leukemia, two Hodgkin's disease, and three other solid tumors. Patients ranged from 7 to 27 years of age at diagnosis of this complication, with a median interval of 25 months (range, 0-11 years) from primary diagnosis. Both steroids and radiation therapy appear implicated in the pathogenesis of avascular necrosis: nine patients had received high cumulative doses of prednisone (3.4-14 g/m2), four had received 35-64.8 Gy local irradiation involving the femoral head, and one underwent total body irradiation (12 Gy). Of the 11 surviving patients, six are asymptomatic and fully active. Two patients have joint pain that is responsive to conservative measures. Severe pain and joint deterioration necessitated arthroplasty in two cases, and a third child is undergoing orthopedic evaluation because of worsening symptoms. Thus, like adult cancer patients, children who receive high doses of steroids or local irradiation involving femoral heads are at risk for avascular necrosis. In patients with chronic myeloid leukemia, the complication may be disease related. Although outcomes in our series are better than those reported in adults, the long period of risk for these children and young adults precludes definitive conclusions.


Organizing a Mass Gathering Amidst a Rising COVID-19 Public Health Crisis: Lessons Learned From a Chinese Public Health Forum in Vancouver, BC.
Introduction The coronavirus disease 2019 (COVID-19) evolved from a rising public health concern to a pandemic over mere weeks. Before March 11, 2020, the Public Health Agency of Canada had not advised against any mass gatherings. Herein, we highlight practical precautions taken by event organizers to adapt to the rising public health threat from COVID-19 and maintain public safety when conducting a health forum for the Chinese community of Vancouver, British Columbia on February 22, 2020. Materials and Methods In the pre-forum phase, we advertised the availability of virtual conferencing for remote participation in the forum and also had an official communication from the Ministry of Health available regarding COVID-19 on our website. At the forum, we ensured that attendees sanitized their hands at registration and had access to sanitizers throughout the forum. Additionally, we provided translated health literature on COVID-19 to participants and had our health professional speakers address COVID-19-related questions. Results This year, 231 older Chinese adults attended the forum in-person, while 150 participated remotely. The total number of 381 participants compares well to previous iterations of the forum, with twice the amount of participants on average attending online than before. Of the participants who attended the forum, 89% suggested that the forum would be effective in improving their overall health and 87% cited the forum's utility in directing them to access community resources. None of the attendees had COVID-19 or are suspected to have contracted it at the forum. Conclusion Conducting a mass gathering during a crisis required closely following guidance from local public health authorities, constant and clear communication with attendees, and employing practical risk mitigation strategies.


Safe medication management and use of narcotics in a Joint Commission International-accredited academic medical center hospital in the People's Republic of China.
Safe medication management and use of high-alert narcotics should arouse concern. Risk management experiences in this respect in a large-scale Joint Commission International (JCI)-accredited academic medical center hospital in the People's Republic of China during 2011-2015, focusing on organizational, educational, motivational, and information technological measures in storage, prescribing, preparing, dispensing, administration, and monitoring of medication are summarized. The intensity of use of meperidine in hospitalized patients in 2015 was one-fourth that in 2011. A 100% implementation rate of standard storage of narcotics has been achieved in the hospital since December 2012. A "Plan, Do, Check, Act" cycle was efficient because the ratio of number of inappropriate narcotics prescriptions to total number of narcotics prescriptions for inpatients decreased from August 2014 to December 2014 (28.22% versus 2.96%, P=0.0000), and it was controlled below 6% from then on. During the journey to good pain management ward accreditation by the Ministry of Health, People's Republic of China, (April 2012-October 2012), the medical oncology ward successfully demonstrated an increase in the pain screening rate at admission from 43.5% to 100%, cancer pain control rate from 85% to 96%, and degree of satisfaction toward pain nursing from 95.4% to 100% (all P-values <0.05). Oral morphine equivalent dosage in the good pain management ward increased from 2.3 mg/patient before June 2012 to 54.74 mg/patient in 2014. From 2011 to 2015, the oral morphine equivalent dose per discharged patient increased from 8.52 mg/person to 20.36 mg/person. A 100% implementation rate of independent double-check prior to narcotics dosing has been achieved since January 2013. From 2014 to 2015, the ratio of number of narcotics-related medication errors to number of discharged patients significantly decreased (6.95% versus 0.99%, P=0.0000). Taken together, continuous quality improvements have been achieved in safe medication management and use of narcotics by an integrated multidisciplinary collaboration during the journey to JCI accreditation and in the post-JCI accreditation era.


Updating Reports of Phase 3 Clinical Trials for Cancer.
Phase 3 randomized clinical trials (RCTs) are usually reported after a predetermined number of events (death or disease progression) have occurred, when survival curves remain poorly defined. Updated reports are important in providing mature data. To evaluate the proportion of phase 3 RCTs for cancer that are updated and the factors that are associated with updating them and, for updated trials, to compare initial and updated results. This study identified reports of 2-group RCTs with a sample size of at least 100, published in 6 major journals between 1990 and 2010, that evaluated drug treatments for breast, lung, or prostate cancer. PubMed and abstracts of large cancer conferences were searched to identify updated (or earlier) reports of the same trials published up to 2019. Logistic regression was used to identify factors associated with the provision of updated reports. The hazard ratios defining the relative treatment effects for the primary and secondary end points between the initial and updated reports were compared. Proportion of RCTs whose results are updated, factors associated with updating, and change in hazard ratio for the primary end point between initial and updated reports. A total of 207 RCTs met the inclusion criteria, and 41 (20%) were found to have updated reports. The factors significantly associated with an update included positive trial results (odds ratio [OR], 8.7 [95% CI, 3.3-23.3]), larger trial size (OR, 1.0006 [95% CI, 1.0000-1.0012]), evaluation of hormonal agents (OR, 5.8 [95% CI, 1.6-21.8]) or targeted agents (OR, 4.3 [95% CI, 1.3-14.6]) compared with chemotherapy, and evaluation of adjuvant therapy rather than therapy for advanced disease (OR, 8.0 [95% CI, 2.9-21.9]). For 31 trials for which initial and updated hazard ratios for the primary end point were available, the median hazard ratio increased from 0.66 (95% CI, 0.22-1.20) to 0.74 (95% CI, 0.32-1.19) (P < .001), indicating a decreased level of effectiveness. Only 20% of reports of phase 3 clinical trials for breast, lung, and prostate cancer were updated. Original reports of such trials are based on relatively few events, and their results are immature; more mature data indicate a decreased level of effect in updated trials. Updated reporting to provide mature, long-term results of clinical trials should be mandated.


Well-defined aminooxy terminated N-(2-hydroxypropyl) methacrylamide macromers for site specific bioconjugation of glycoproteins.
Syntheses and characterization of aminooxy terminated polymers of N-(2-hydroxyproyl) methacrylamide (HPMA) of controlled molecular weight and narrow molecular weight distribution are presented here. Design of a chain transfer agent (CTA) containing N-tert-butoxycarbonyl (t-Boc) protected aminooxy group enabled us to use reversible addition-fragmentation (RAFT) polymerization technique to polymerize the HPMA monomer. An amide bond was utilized to link the aminooxy group and the CTA through a triethylene glycol spacer. As a result, the aminooxy group is linked to the poly(HPMA) backbone through a hydrolytically stable amide bond. By varying the monomer to initiator ratios, polymers with targeted molecular weights were obtained. The molecular weights of the polymers were determined by gel permeation chromatography (GPC) and mass spectrometry (ESI and MALDI-TOF). The t-Boc protecting group was quantitatively removed to generate aminooxy terminated poly(HPMA) macromers. These macromers were converted to rhodamine B terminated poly(HPMA) by reacting N-hydroxysuccinimide (NHS) ester of the dye with the terminal aminooxy group to form a stable alkoxyamide bond. Utility of these dye-labeled polymers as molecular probes was evaluated by fluorescence microscopy by studying their intracellular uptake by renal epithelial cells. These aminooxy terminated poly(HPMA) were also tested as biocompatible carriers to prepare chemoselective bioconjugates of proteins using transferrin (Tf) as the protein. Oxidation of the sialic acid side chains of Tf generated aldehyde functionalized protein that was reacted with aminooxy terminated poly(HPMA), which resulted in protein-polymer bioconjugates carrying oxime linkages. These bioconjugates were characterized by gel electrophoresis and MALDI-TOF mass spectrometry.


Endogenous epidermal growth factor regulates limb development.
Mutations associated with genes of the EGF superfamily are implicated in limb malformations. To evaluate the potential role of EGF-mediated signal transduction in the control of early mammalian limb development, we developed a simple in vitro system which is permissive for morphogenesis and cytodifferentiation in serumless, chemically defined medium. Our experimental strategy was to ascertain if the EGF precursor gene was transcribed and translated into potentially bioactive growth factor. EGF mRNA transcripts are expressed in Swiss Webster mouse embryonic (42-44 somite pairs) forelimbs as determined by mRNA phenotyping. EGF transcripts are translated into precursor EGF polypeptides which were localized to limb covering epithelium and the chondrogenic mesenchymal cell lineages. EGF immunostaining patterns suggested a paracrine type of regulation for the cartilage blastema associated with forelimb development. To test whether EGF effects the timing and positional information required for limb-specific cartilage morphogenesis, we employed tyrphostin (RG 50864) which inhibits EGF receptor kinase activity in a concentration-dependent manner and severely retards limb development. These findings support our hypothesis that endogenous EGF or EGF-like proteins provide signaling for the size and shape of discrete forelimb cartilage formations during mouse embryonic morphogenesis.


The newer unconventional indications of permanent pacemakers.
In recent years, the indications for permanent pacemakers have expanded. The interest has focussed on hypertrophic cardiomyopathy, dilated cardiomyopathy and a new entity called hypertensive hypertrophy with cavity obliteration (HHCO). Pacemaker therapy is establishing itself for the prevention of atrial fibrillation. Pacing for neurocardiogenic syncope with newer pacing mode has encouraging datas. Pacemaker for long QT syndrome, after cardiac transplant and for haemodynamic improvement in occasional cases of first degree atrio-ventricular block is getting attention. The AHA and ACC guidelines updated in 1998 for implantation of cardiac pacemakers, now include several of these newer indications.


Acculturation and enculturation as predictors of psychological help-seeking attitudes (HSAs) among racial and ethnic minorities: A meta-analytic investigation.
Psychological services are culturally encapsulated for dominant cultural groups, and racial minorities underutilize treatment even though they suffer from more severe psychological distress. Sociocultural factors such as acculturation (one's adaptation into mainstream group) and enculturation (one's adherence to culture of heritage) are hypothesized to affect minorities' attitudes toward seeking psychological services. This meta-analysis examined 3 methods to assess acculturation/enculturation-unidimensional acculturation, bidimensional acculturation, and bidimensional enculturation as predictors of help-seeking attitudes (HSAs)-both positive and negative attitudes-among racial and ethnic minorities in 207 samples drawn from 111 research reports. The omnibus correlations between acculturation/enculturation variables and HSAs were quite small, but in the predicted direction. Moderator analyses suggested a more nuanced understanding of the association between bidimensional enculturation and positive HSAs: This association was significant (r = -.14 95% CI[-.18, -.09]) for Asians and Asian Americans, but very close to zero and nonsignificant for other racial minority groups (African Americans, Latino Americans, and others). In addition, the domain of acculturation/enculturation assessed was predictive of effect size, with enculturation measures containing a higher proportion of cognitive items (e.g., items that assess cultural values and beliefs) showing stronger (more negative) associations with positive HSAs. Post hoc analyses indicated that certain Asian cultural values, including emotional self-control, conformity to social norms, and collectivism, showed especially high negative associations with positive HSAs. (PsycINFO Database Record


Usage of neck circumference as novel indicator of erectile dysfunction: a pilot study in Turkish population.
Erectile dysfunction (ED) is the most common male sexual problem worldwide. The association between ED and components of metabolic syndrome (MtS) is well established. This study examined neck circumference (NC) as a possible indicator of MtS and also of ED. Ninety-two patients were included and divided into two groups. Group 1 consisted of 47 patients with ED and Group 2 consisted of 45 healthy volunteers. Questionnaires, differences in anthropometric and laboratory measurements between patients with ED and the control group, and a cut-off value for NC were investigated. The mean NC in ED patients was higher in Group 1 than in Group 2 (P = 0.001), and Group 1 also demonstrated more MtS criteria than Group 2 (P < 0.001). The cut-off point of NC was defined as 34.75 cm for ED and MtS. The cut-off values of waist circumference for ED and MtS were 105.5 and 102.5 cm respectively. In the light of these findings, NC may be a new component of MtS in ED patients. Additionally, NC may be a novel indicator of central obesity and ED. We suggest that NC values of 35 cm and over may predict ED in patients with MtS.


Expression of p53 gene in 184 unifocal hepatocellular carcinomas: association with tumor growth and invasiveness.
To elucidate the biological significance of the p53 gene expression in human hepatocellular carcinoma (HCC), the p53 protein was studied in 184 resected unifocal primary HCCs, including 102 small (< or = 5 cm) and 82 large HCCs (> 5 cm), using immunocytochemistry. The p53 mRNA expression was analyzed in 69 cases using Northern hybridization. The p53 protein, which was detected in 58 HCCs (31.5%), was overexpressed more frequently in HCC with elevated serum alpha-fetoprotein level (37.9 versus 25%, P < 0.04), in large HCC (39.0 versus 25.5%, P < 0.03), and in invasive HCC (35.1 versus 13.3%, P < 0.01). The overexpression of p53 protein closely correlated with p53 mRNA overexpression (75 versus 44.4%, P < 0.003), and p53 gene mutation (76.9 versus 19.2%, P < 1 x 10(-9)). HCCs with p53 protein expression (group A) and those negative for both p53 protein and mRNA expression (group B) had an unfavorable outcome, while HCC with no p53 protein but with p53 mRNA overexpression (group C) had the best outcome; the 4-year survival was 26.1, 26.3, and 62.5%, respectively. The p53 gene mutation was significantly higher in group A HCC (76.9%) than in groups B (27.3%) and C (23.5%), P < 0.0001. The results suggest that the p53 protein and mRNA expression patterns in HCC correlate with p53 gene mutation and tumor behavior and may serve as a molecular prognostic factor.


Classification of miRNA-related sequence variations.
miRNA regulome is whole set of regulatory elements that regulate miRNA expression or are under control of miRNAs. Its understanding is vital for comprehension of miRNA functions. Classification of miRNA-related genetic variability is challenging because miRNA interact with different genomic elements and are studied at different omics levels. In the present study, miRNA-associated genetic variability is presented at three levels: miRNA genes and their upstream regulation, miRNA silencing machinery and miRNA targets. Several types of miRNA-associated genetic variations are known, including short and structural polymorphisms and epimutations. Differential expression can also affect miRNA regulome function. Classification of miRNA-associated genetic variability presents a baseline for complementing sequence variant nomenclature, planning of experiments, protocols for multi-omics data integration and development of biomarkers.


[The war and refugees in former Yugoslavia].
The author describes the status of refugees displaced by the war in Yugoslavia. It is concluded that "the flight and displacements of population are not only the consequence of the war but also one of its aims: [to] produce ethnically 'pure' territories." Data mainly concern the period from late 1991 to the present. (SUMMARY IN ENG AND GER)


Oral health and dental care of elderly adults dependent on care.
The increase in life expectancy in Switzerland is posing new challenges, as more and more people are becoming dependent on care, both at home and in long-term care facilities. The dental profession must deal with patients retaining their own teeth until later in life with an increased incidence and severity of caries and periodontal diseases. The association between general and oral health is becoming important, particularly in older people with medical conditions. Aspiration pneumonia can develop as a result of pathogenic bacteria descending from the oral cavity to the bronchoalveolar system, which presents a frequent, potentially life-threatening danger. By adapting care and treatment concepts, the masticatory ability can be preserved or restored, which in turn helps preventing malnutrition. Other aims include preventing infections as well as maintaining subjective well-being and an attractive dental appearance. Care standards should be defined for the provision of oral-health related dentistry for the vulnerable population of the care-dependent adults. These should be implemented by an interdisciplinary care team composed of nursing personnel, long-term care facility managers, Spitex staff, physicians, dentists as well as dental assistants and hygienists.


Antiplatelet and Anticoagulation Treatment in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome: Comparison of the Updated North American and European Guidelines.
In 2014, the American Heart Association and the American College of Cardiology (AHA/ACC) published their guideline for the management of patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS), whereas the European Society of Cardiology published their latest guideline for the management of patients with NSTE-ACS in 2011. In this article, we review the main updates in antiplatelet and anticoagulation therapy in the 2014 AHA/ACC guideline and compare them with the 2011 European guidelines. Key recommendations in the AHA/ACC guidelines include the addition of ticagrelor to a broad spectrum of patients with NSTE-ACS, narrowing of the role of prasugrel to patients who undergo coronary stenting, and limiting the use of glycoprotein IIb/IIIa receptor inhibitors mainly to high-risk patients during percutaneous coronary intervention. These modifications bring the North American and the European guidelines closer together. The recommendations regarding anticoagulants still differ between the 2 guidelines, although all 4 parenteral agents (unfractionated heparin, low-molecular-weight heparin, bivalirudin, and fondaparinux) are now considered acceptable by both guidelines. We also review new data from clinical trials that became available after the 2014 guidelines were finalized, including studies with cangrelor, rivaroxaban, vorapaxar, ticagrelor, and long-term use of dual antiplatelets that will be considered in future guidelines. As the 2014 guidelines represent the most comprehensive and authoritative document for the management of patients with NSTE-ACS, clinicians who manage these patients should be familiar with their recommendations to ensure optimal patient care.


Comparison of contralateral oblique view with the lateral view for fluoroscopic-guided cervical epidural steroid injection: a randomized clinical trial.
Cervical epidural steroid injection is associated with rare but potentially catastrophic complications. The contralateral oblique (CLO) view may be a safe and feasible alternative to the lateral (LAT) view for fluoroscopic-guided cervical epidural steroid injection. However, evidence for the clinical usefulness of the CLO view for cervical epidural steroid injection is lacking. We assessed the clinical usefulness of the CLO view for cervical epidural steroid injection in managing cervical herniated intervertebral discs. Patients were randomly assigned to receive fluoroscopic-guided cervical epidural steroid injection under LAT view or CLO view at 50±5° degrees groups. The primary outcome was the needling time comparison between the two groups. Secondary outcomes were comparison of first-attempt success rate, needle tip visualization and location, total number of needle passes, final success rate, crossover success rate and false-positive/negative loss of resistance. Complications and radiation dose were also compared. The needling time significantly decreased in the CLO than in the LAT group. The first-attempt success rate was significantly higher in the CLO compared with the LAT group. The needle tip was clearly visualized (p<0.001) and located more often on (or just anterior to) the ventral interlaminar line (p<0.001) in the CLO than in the LAT group. There were significantly fewer needle passes (p=0.019) in the CLO than in the LAT group. There were no significant differences in the final success, crossover success, false-positive/negative loss of resistance or radiation dose between the groups. Two (5.9%) cases in the LAT group experienced complications. The CLO view may be recommended for fluoroscopic-guided cervical epidural steroid injection, considering its better clinical usefulness over the LAT view.


CHAOS: A fetal autopsy report.
Congenital high airway obstruction syndrome (CHAOS) is a rare congenital malformation, which results from deficient recanalization of the upper airways. Laryngeal atresia is the most common cause, other etiologies being trachea atresia, laryngeal or tracheal webs, subglottic stenosis, obstructing laryngeal cysts, and laryngeal or tracheal agenesis. There is decreased clearance of the fluid produced by fetal lungs due to obstruction leading to increased intratracheal pressure and thereby secondary proliferative lung growth. The heart becomes compressed in the midline due to hyperexpansion of the lungs causing elevated intrathoracic pressure, decreased venous return, and fetal cardiac failure. This sequence causes ascites, placento-megaly, and eventually hydrops fetalis. We present a case of antenatal diagnosis of a fetus with CHAOS corroborated by fetal autopsy.


[Epidemiological studies on multiple primary malignant tumors in Nagasaki City].
Ninety-four cases of multiple primary malignant tumors registered at the Nagasaki Tumor Registry during the period from 1973-1977 were studied. The crude incidence rate tended to be higher in atomic bomb survivors although the difference was not significant. The male:female ratio was 1:1.19. Cases in the sixth decade of life were dominant, the average age was somewhat lower in females than in males. Stomach cancer was observed in 48 patients (51.1%; triple malignancies in 8 cases (8.5%).


Beta microseminoprotein is not a prostate-specific protein. Its identification in mucous glands and secretions.
Beta microseminoprotein (beta inhibin, PSP94), an unglycosylated protein of 94 amino acids with unknown function, is one of the predominating proteins in the secretion of the human prostate gland. In this work the authors have demonstrated that the expression of beta microseminoprotein is not restricted to the prostate and that the protein has a previously unrecognized widespread occurrence in the human body. According to radioimmunoassay, beta microseminoprotein immunoreactivity is present in many nonprostatic body fluids. The highest concentrations were found in secretions from the respiratory tract; in tracheobronchial fluid sometimes even at concentrations comparable to that in seminal plasma (about 1 g/l). Intermediate concentrations were found in gastric juice and some samples of secretion from the uterine cervix, whereas tears, saliva, pancreatic juice, bile, and mucus from the colon had low concentrations. According to gel chromatography, the molecular size of the beta microseminoprotein immunoreactivity present in tracheal fluid, gastric juice, and secretion from the uterine cervix did not differ from that of beta microseminoprotein in seminal plasma. The beta microseminoprotein immunoreactive component present in gastric juice had the same amino-terminal amino acid sequence as prostatic beta microseminoprotein (14 residues identified in material purified from gastric juice), providing further evidence for chemical identity of a nonprostatic beta microseminoprotein with the prostatic protein. Immunohistochemical staining with affinity-purified antibodies demonstrated the presence of beta microseminoprotein in many tissues, including the goblet cells in the tracheobronchial epithelium, tracheobronchial submucosal glands, certain mucosal cells in the antrum of the stomach, some glands of Brunner in the duodenum, and in parts of the mucosa of the colon. At least in the respiratory tract, the staining was localized to mucus-containing cells. beta microseminoprotein immunoreactivity also was localized to the cilia of the ciliated epithelium in the respiratory tract, the fallopian tubes, and the Gartner ducts of the uterine cervix. The pattern of tissue distribution of beta microseminoprotein found in this work indicates a connection of beta microseminoprotein with mucous secretions.


Prolonged rewarding stimulation of the rat medial forebrain bundle: neurochemical and behavioral consequences.
Extracellular dopamine levels were measured in the rat nucleus accumbens by means of in vivo microdialysis. Delivery of rewarding medial forebrain bundle stimulation at a low rate (5 trains/min) produced a sustained elevation of dopamine levels, regardless of whether train onset was predictable. When the rate of train delivery was increased to 40 trains/min, dopamine levels rose rapidly during the first 40 min but then declined toward the baseline range. The rewarding impact of the stimulation was reduced following prior delivery of stimulation at the high, but not the low, rate. These results support the idea that dopamine tone plays an enabling role in brain stimulation reward and is elevated similarly by predictable and unpredictable stimulation.


p16 expression in primary malignant melanoma is associated with prognosis and lymph node status.
Lymph node (LN) status is an important prognostic factor in melanoma patients. p16 expression and proliferation rate (MIB-1) of primary melanomas have been suggested as a marker of metastatic potential. In this study, the correlation of p16 expression and the proliferation rate (MIB-1) with LN status and tumor-specific survival was investigated in primary melanomas. MIB-1 and p16 expression were analyzed by immunohistochemistry in 64 patients with primary cutaneous melanoma. Thirty four nevi were used as control. All patients underwent sentinel lymph node staging. Three different p16 staining patterns were observed: a combination of nuclear and cytoplasmic staining, only cytoplasmic staining and absence of p16 expression. All 34 nevi displayed a nuclear and cytoplasmic p16 staining, whereas p16 was negative in 14 of 64 (22%) melanomas. The level of p16 expression gradually decreased from benign nevi to melanoma without metastasis to melanoma with metastasis. There was a significant correlation between cytoplasmic p16 expression and absence of metastasis (p < 0.05). Death of disease correlated with absence of p16 immunostaining (p = 0.01). MIB-1 expression was not associated with survival. These results confirm the relevance of p16 expression as a prognostic marker in melanoma patients. In addition, it was shown that cytoplasmic immunostaining for p16 in primary melanoma might serve as a predictor of the LN status. Therefore, immunohistochemical evaluation for p16 expression is of potential value for treatment planning in melanoma surgery.


Effect of hemodilution on capillary and arteriolovenous shunt flow in organs after cardiac arrest in dogs.
The purpose of this study was to observe the changes in capillary and arteriolovenous shunting blood flow after cardiac arrest and subsequent resuscitation by venous return occlusion produced by inflation of an intra-atrial balloon and cross-clamping of the ascending aorta, and to determine how hemodilution might modify such changes. Organ capillary blood flow and the fractional distribution of cardiac output were measured by the microsphere (9-microns diameter) trapping method in dogs. Simultaneously, the arteriolovenous shunt rate was measured by continuous collection of venous blood drained at 4.8 ml.min-1 for 2 min from the brain, kidney, liver, splanchnic organs, skeletal muscle of the pelvic limb, and all of the systemic circulatory organs. The capillary blood flow of the brain, thyroid gland, pancreas, and stomach decreased after circulatory arrest in five nonhemodiluted dogs (group C); arteriolovenous shunt rate was unchanged after circulatory arrest in this group. However, with hemodilution, which was induced either before (pre group, n = 5) or after (post group, n = 5) circulatory arrest, no change occurred in the shunt rate in any of the organs, with the exception of an increase in the systemic arteriolovenous shunt rate in the pre group. Capillary blood flow was maintained at almost the same level as before circulatory arrest in the pre group, but increased significantly in several organs of the post group. The data indicated that hemodilution might be effective for prevention of organ ischemia after cardiac arrest.


Inhibitory effects of trospium chloride on cytochrome P450 enzymes in human liver microsomes.
Trospium chloride, an atropine derivative used for the treatment of urge incontinence, was tested for inhibitory effects on human cytochrome P450 enzymes. Metabolic activities were determined in liver microsomes from two donors using the following selective substrates: dextromethorphan (CYP2D6), denitronifedipine (CYP3A4), caffeine (CYP1A2), chlorzoxazone (CYP2E1), S-(+)-mephenytoin (CYP2C19), S-(-)-warfarin (CYP2C9) and coumarin (CYP2A6). Incubations with each substrate were carried out without a possible inhibitor and in the presence of trospium chloride at varying concentrations (37-3000 microM) at 37 degrees in 0.1 M KH2PO4 buffer containing up to 3% DMSO. Metabolite concentrations were determined by high-performance liquid chromatography (HPLC) in all cases except CYP2A6 where direct fluorescence spectroscopy was used. First, trospium chloride IC50 values were determined for each substrate at respective K(M) concentrations. Trospium chloride did not show relevant inhibitory effects on the metabolism of most substrates (IC50 values considerably higher than 1 mM). The only clear inhibition was seen for the CYP2D6-dependent high-affinity O-demethylation of dextromethorphan, where IC50 values of 27 microM and 44 microM were observed. Therefore, additional dextromethorphan concentrations (0.4-2000 microM) were tested. Trospium chloride was a competitive inhibitor of the reaction with Ki values of 20 and 51 microM, respectively. Thus, trospium chloride has negligible inhibitory effects on CYP3A4, CYP1A2, CYP2E1, CYP2C19, CYP2C9 and CYP2A6 activity but is a reasonably potent inhibitor of CYP2D6 in vitro. Compared to therapeutic trospium chloride peak plasma concentrations below 50 nM, the 1000-times higher competitive inhibition constant Ki however suggests that inhibition of CYP2D6 by trospium chloride is without any clinical relevance.


Pain Treatment of Underserved Older African Americans.
Older African Americans who experience pain are especially at high risk of underassessment and undertreatment. This study examined patterns and correlates of pain medication use: severity of pain, medical conditions, and access to care. African Americans aged 65 and older were recruited from 16 churches located in south Los Angeles (N = 400). Structured face-to-face interviews and visual inspection of each participant's medications were conducted. More than 39% of participants were aged 75 and older, and 65% were female. Forty-seven percent used at least one type of pain medication. The frequency of pain medication use according to pharmaceutical class was nonopioid, 33%; opioid, 12%; adjuvant, 9%; and other drug, 8%. Seventy-seven percent of nonopioids were nonsteroidal anti-inflammatory drugs (NSAIDs), which 25% of participants with hypertension, 28% with stroke, 26% with kidney disease, and 28% with gastrointestinal problems used. Ninety-eight percent of participants who used NSAIDs, 98% experienced potentially inappropriate medication (PIM) use, 69% experienced drug duplication, and 65% experienced drug-drug interactions. This study suggests severe mismanagement of pain in underserved older African Americans, particularly those with comorbidity, multiple providers, and limited access to health care. The use of pain medication was associated with drug-drug interactions, drug duplication, and PIM use. The data show that many participants with severe pain are not taking pain medication or experience PIM use. One in four participants was taking NSAIDs, which can cause serious side effects in older African Americans with multiple chronic conditions.


Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase.
The Sod2 gene for Mn-superoxide dismutase (MnSOD), an intramitochondrial free radical scavenging enzyme that is the first line of defense against superoxide produced as a byproduct of oxidative phosphorylation, was inactivated by homologous recombination. Homozygous mutant mice die within the first 10 days of life with a dilated cardiomyopathy, accumulation of lipid in liver and skeletal muscle, and metabolic acidosis. Cytochemical analysis revealed a severe reduction in succinate dehydrogenase (complex II) and aconitase (a TCA cycle enzyme) activities in the heart and, to a lesser extent, in other organs. These findings indicate that MnSOD is required for normal biological function of tissues by maintaining the integrity of mitochondrial enzymes susceptible to direct inactivation by superoxide.


Incidence of Vitis fruit-induced clinical signs and acute kidney injury in dogs and cats.
To determine the incidence of clinical signs and Vitis fruit-induced acute kidney injury in dogs and cats with a Vitis fruit ingestion reported to the Dutch Poisons Information Center, and a description of the therapies instituted by the veterinarians. All cases of Vitis fruit ingestions in dogs and cats reported to the center between January 1, 2018 and December 31, 2018 were included in this study. Veterinarians and pet owners were contacted by phone or email to obtain follow-up information. Information was collected using a standardised data collection sheet. Ninety-five dogs and 13 cats with proven Vitis fruit ingestion were included. Fourteen dogs and two cats developed clinical signs: emesis (11/16, 68.8%), lethargy (5/16, 31.3%), diarrhoea (3/16, 18.8%), anorexia (3/16, 18.8%), tremor (2/16, 12.5%) and restlessness (1/16, 6.3%). The overall incidence for developing clinical signs was 14.7% in dogs and 15.4% in cats. One (1/95, 1%) dog developed acute kidney injury after ingestion of Vitis fruit. No cats developed acute kidney injury. Induction of emesis and/or administration of activated charcoal was instituted in 72 of 82 (88%) and eight of 11 (73%) of asymptomatic dogs and cats and six of 14 (43%) and two of two (100%) of symptomatic dogs and cats, respectively. Overall, emesis was induced in 72 of 95 (76%) dogs (100% success rate) and removed Vitis fruits in the majority of cases (98% when induced <4 hours after ingestion and 83% when induced 4 to 12 hours after ingestion). Emesis was induced in seven of 13 (54%) cats (86% success rate) and removed Vitis fruits in 83% of the cases. In this study, a significant proportion (around 15%) of dogs and cats developed clinical signs after ingestion of Vitis fruits, which were predominantly related to the gastrointestinal tract. Symptomatic acute kidney injury was rare. Our findings suggest the use of decontamination measures, i.e. induction of emesis, may be warranted up to 12 hours after ingestion.


Exploring virtual mental practice in maintenance task training.
- This paper aims to contribute to a general understanding of mental practice by investigating the utility of and participant reaction to a virtual reality maintenance training among underground coal mine first responders. - Researchers at the National Institute for Occupational Safety and Health's Office of Mine Safety and Health Research (OMSHR) developed software to provide opportunities for mine rescue team members to learn to inspect, assemble and test their closed-circuit breathing apparatus and to practice those skills. In total, 31 mine rescue team members utilized OMSHR's BG 4 Benching Trainer software and provided feedback to the development team. After training, participants completed a brief post-training questionnaire, which included demographics, perceived training climate and general training evaluation items. - The results overall indicate a generally positive reaction to and high perceived utility of the BG 4 benching software. In addition, the perceived training climate appears to have an effect on the perceived utility of the mental practice virtual reality game, with benchmen from mines with more positive training climates reporting greater perceived efficacy in the training's ability to prepare trainees for real emergencies. - This paper helps to broaden current applications of mental practice and is one of the few empirical investigations into a non-rehabilitation virtual reality extension of mental practice. This paper also contributes to the growing literature advocating for greater usage of accurate and well-informed mental practice techniques, tools and methodologies, especially for occupational populations with limitations on exposure to hands-on training.


Phenomenology in need of treatment: commentary for the special series "Narcissistic personality disorder--new perspectives on diagnosis and treatment".
Comments on the articles by A. E. Skodol et al. (see record 2013-24395-001), E. Ronningstam (see record 2014-42878-005), D. Diamond et al. (see record 2014-42878-004), and A. L. Pincus et al. (see record 2014-01439-001). Good delineation of the phenomenology of narcissistic personality disorder (NPD) is necessary but insufficient for informing us on what to do clinically. Perry suspects that we will see reams of publications comparing Section III and II diagnoses with various external measures and possibly experimental procedures. We will learn some important things, along with many facts without actionable consequences. However, because NPD does not show many differential relationships to particular functional measures, I believe that treatment studies will likely be the most informative.


1H NMR and circular dichroism studies of the N-terminal domain of cyclic GMP dependent protein kinase: a leucine/isoleucine zipper.
Cyclic GMP dependent protein kinase exists as a dimer in its native form. A peptide corresponding to the dimerization domain in the N-terminal segment has been characterized by circular dichroism, ultracentrifugation, and 1H NMR spectroscopy. The peptide (G-kinase1-39 amide) is shown to be dimeric in solution. Determination of the molecular weight of the species in solution from the sedimentation coefficient and diffusion coefficient yields a value more than twice that of the monomeric species. Circular dichroism studies show G-kinase1-39 amide to be largely helical in aqueous solution and stable over a wide range of pH and temperature. The conformational stability is found to be concentration dependent, the peptide having a melting temperature of 75 degrees C (at 20 microM and pH 4.0). The assignment of the 1H NMR spectrum and analysis of the patterns of nuclear Overhauser enhancements confirm the helical nature of the conformation. Distance geometry calculations result in a well-defined helical structure containing a kink near Ser 26. The dimerization of G-kinase is most likely to occur through the hydrophobic interaction of leucine and isoleucine side chains located on one face of a helical structure with supporting electrostatic interactions between flanking side chains. The dimerization domain of G-kinase is clearly analogous to the "leucine zipper" motifs found in a number of DNA transcriptional activators.


Quasi-confocal, multichannel parallel scan hyperspectral fluorescence imaging method optimized for analysis of multicolor microarrays.
The microarray technique, which can provide parallel detection with high throughput in biomedical research, has generated considerable interest since the end of the 20th century. A number of instruments have been reported for microarray detection. In this paper, we have developed a quasi-confocal, multichannel parallel scan hyperspectral fluorescence imaging system for multicolor microarray research. Hyperspectral imaging records the entire emission spectrum for every voxel within the imaged area in contrast to recording only fluorescence intensities of filter-based scanners. When coupled with data analysis, the recorded spectral information allows for quantitative identification of the contributions of multiple, spectrally overlapping fluorescent dyes and elimination of unwanted artifacts. This system is improved with a specifically designed, high performance spectrometer which can offer a spectral resolution of 0.2 nm and operates with spatial resolutions ranging from 2 to 30 μm. We demonstrate the application of the system by reading out arrays for identification of bacteria.


Ca2+/calmodulin-dependent protein kinase II: identification of autophosphorylation sites responsible for generation of Ca2+/calmodulin-independence.
Ca2+/calmodulin-dependent protein kinase II contains two types of subunit, alpha (Mr 50,000) and beta (Mr 60,000/58,000), both of which undergo Ca2+/calmodulin-dependent autophosphorylation. Autophosphorylation is known to convert the enzyme to a Ca2+/calmodulin-independent form. In the present study, we have characterized the autophosphorylation sites on rat forebrain Ca2+/calmodulin-dependent protein kinase II that are most likely to be responsible for the generation of Ca2+/calmodulin-independence. Under conditions (0 degree C, low concentrations of ATP) sufficient to generate close to maximal Ca2+/calmodulin-independence, only a few of the phosphorylatable sites on the enzyme became phosphorylated. These autophosphorylation sites were examined by phospho amino acid analysis, two-dimensional thermolytic phosphopeptide mapping, and high-performance liquid chromatography. The time course of phosphorylation of threonine in both alpha and beta subunits was similar to the time course of the generation of Ca2+/calmodulin-independence. Moreover, the time course of phosphorylation of one set of peptides, referred to as peptide 1/1', present in both alpha and beta subunits was similar to the time course of the generation of Ca2+/calmodulin-independence. Threonine was the only amino acid phosphorylated in peptide 1/1'. An additional peptide, referred to as peptide 2, was phosphorylated in the beta subunit. The time course of phosphorylation of peptide 2, which also contained only phosphothreonine, did not parallel the time course of the generation of Ca2+/calmodulin-independence. It is likely that the phosphorylation of a threonine residue on peptide 1/1' is responsible for the generation of Ca2+/calmodulin-independence of Ca2+/calmodulin-dependent protein kinase II.


TAK1 regulates resident macrophages by protecting lysosomal integrity.
Hematopoietic cell survival and death is critical for development of a functional immune system. Here, we report that a protein kinase, TAK1, is selectively required for resident macrophage integrity during embryogenesis. Hematopoietic lineage-specific deletion of Tak1 gene (Tak1HKO) caused accumulation of cellular debris in the thymus in perinatal mice. Although no overt alteration in thymocytes and blood myeloid populations was observed in Tak1HKO mice, we found that thymic and lung macrophages were diminished. In the in vitro setting, Tak1 deficiency caused profound disruption of lysosomes and killed bone marrow-derived macrophages (BMDMs) without any exogenous stressors. Inhibition of the lysosomal protease, cathepsin B, partially blocked Tak1-deficient BMDM death, suggesting that leakage of the lysosomal contents is in part the cause of cell death. To identify the trigger of this cell death, we examined involvement of TNF and Toll-like receptor pathways. Among them, we found that deletion of Tnfr1 partially rescued cell death. Finally, we show that Tnfr1 deletion partially restored thymic and lung macrophages in vivo. These results suggest that autocrine and potentially paracrine TNF kills Tak1-deficient macrophages during development. Our results reveal that TAK1 signaling maintains proper macrophage populations through protecting lysosomal integrity.


Lung epithelial NF-kappaB and Stat1 signaling in response to CD8+ T cell antigen recognition.
CD8+ T cell recognition of viral antigens presented by lung epithelial cells is important in the clearance of respiratory viral infection but may cause considerable injury to the lung. We have shown that a critical event of this type of injury is the activation of target epithelial cells and expression of chemokines by these cells. In this study, epithelial gene expression and transcription factor activation triggered by specific CD8+ T cell antigen recognition was examined in vitro and in vivo. T cell recognition triggers expression profiles of tumor necrosis factor-alpha (TNF-alpha)-dependent and interferon-gamma (IFN-gamma)-dependent genes in epithelial target cells. Consistent with these profiles, transcription factors nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) were activated in lung epithelial cells of wild-type (WT) mice but not TNF receptor 1 (TNFR1)-deficient mice after CD8+ T cell recognition in vivo. In contrast, Stat1 activation and Stat1-dependent genes, such as IFN regulatory factor-1 (IRF-1) and guanylate-binding protein-2 (GBP-2), were induced to a similar extent in epithelial cells of both WT and TNFR1-deficient mice, indicating that this pathway is insufficient to induce pulmonary immunopathology in the absence of NF-kappaB-dependent transcriptional activation. Antibody neutralization of TNF-alpha abrogated epithelial monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) production in vitro as well as pulmonary immunopathology in vivo, confirming the primary importance of this cytokine in CD8+ T cell-mediated immunopathology.


Redox control of the catalytic cycle of flavocytochrome P-450 BM3.
Flavocytochrome P-450 BM3 from Bacillus megaterium is a 119 kDa polypeptide whose heme and diflavin domains are fused to produce a catalytically self-sufficient fatty acid monooxygenase. Redox potentiometry studies have been performed with intact flavocytochrome P-450 BM3 and with its component heme, diflavin, FAD, and FMN domains. Results indicate that electron flow occurs from the NADPH donor through FAD, then FMN and on to the heme center where fatty acid substrate is bound and monooxygenation occurs. Prevention of futile cycling of electrons is avoided through an increase in redox potential of more than 100 mV caused by binding of fatty acids to the active site of P-450. Redox potentials are little altered for the component domains with respect to their values in the larger constructs, providing further evidence for the discrete domain organization of this flavocytochrome. The reduction potentials of the 4-electron reduced diflavin domain and 2-electron reduced FAD domain are considerably lower than those for the blue FAD semiquinone species observed during reductive titrations of these enzymes and that of the physiological electron donor (NADPH), indicating that the FAD hydroquinone is thermodynamically unfavorable and does not accumulate under turnover conditions. In contrast, the FMN hydroquinone is thermodynamically more favorable than the semiquinone.


Untargeted metabolic quantitative trait loci analyses reveal a relationship between primary metabolism and potato tuber quality.
Recent advances in -omics technologies such as transcriptomics, metabolomics, and proteomics along with genotypic profiling have permitted dissection of the genetics of complex traits represented by molecular phenotypes in nonmodel species. To identify the genetic factors underlying variation in primary metabolism in potato (Solanum tuberosum), we have profiled primary metabolite content in a diploid potato mapping population, derived from crosses between S. tuberosum and wild relatives, using gas chromatography-time of flight-mass spectrometry. In total, 139 polar metabolites were detected, of which we identified metabolite quantitative trait loci for approximately 72% of the detected compounds. In order to obtain an insight into the relationships between metabolic traits and classical phenotypic traits, we also analyzed statistical associations between them. The combined analysis of genetic information through quantitative trait locus coincidence and the application of statistical learning methods provide information on putative indicators associated with the alterations in metabolic networks that affect complex phenotypic traits.


CD21lo/medCD27+ proinflammatory B cells are enriched in breast cancer patients and promote antitumor T cell responses.
Breast cancer is a common malignancy and a major cause of death in women worldwide. The immunomodulatory role of B cells is being increasingly recognized in autoimmune diseases and cancers. In recent years, immunotherapeutic strategies that upregulate the patient's own antitumor T cell responses have shown promise in treating solid tumors and are being developed for breast cancer. In this study, we discovered that the B cells in breast cancer patients were enriched with interferon (IFN)-γ-expressing cells and presented high potency for IFN-γ production. These IFN-γ-expressing B cells were enriched in, but did not completely overlap with, the CD21lo/medCD27+IgM-IgD-IgG+IgA- B cell subset, which was consistent with IgG-expressing memory B cells. Compared to CD27+IgG- B cells, the CD27+IgG+ B cells expressed significantly higher IFN-γ expression. Given that B cells demonstrate important antigen-presenting function to T cells, we incubated CD27+IgG- B cells and CD27+IgG+ B cells with autologous CD4+ T cells. Compared to the CD4+ T cells that were incubated with CD27+IgG- B cells, the CD4+ T cells that were incubated with CD27+IgG+ B cells presented significantly higher TBX21 and lower FOXP3 expression, suggesting that the CD27+IgG+ B cells, but not the CD27+IgG- B cells, promoted Th1 and suppressed regulatory T cell responses. IFN-γ-expressing B cells were further enriched in the intratumoral environment of breast cancer patients. Together, we discovered that breast cancer patients presented an upregulation of IFN-γ-expressing proinflammatory B cells with the potency to promote Th1 responses.


Considerations on the effect of anti-sandfly antibodies on biological parameters of Lutzomyia longipalpis (Lutz & Neiva, 1912) (Diptera: Psychodidae: Phlebotominae).
The immunization of vertebrate hosts with vector components may be an alternative for the control of diseases transmitted by insects. In the present study we evaluated the effects of anti-sandfly antibodies on some of the biological parameters of female Lutzomyia longipalpis, a vector of visceral leishmaniasis. Rabbits were immunized with extracts of gut from blood-fed (GB) or sugar-fed (GS) females, carcass of sugar-fed (CS) or blood-fed (CB) females, and with repeated sandfly bites (BITE). Immune sera showed increased antibody titers compared to pre-immunized animals, and specific bands were detected by Western Blot. An analysis of biological parameters revealed a decline in fecundity in the group of females fed on rabbits immunized with GB and BITE. Longevity and mortality were studied in females with oviposition (parous) and without oviposition (nulliparous). Nulliparous females that fed on rabbits immunized with bites died in the highest percentage. A mortality analysis after egg laying revealed a peak on the fifth day in all the groups, but females fed on rabbit subjected to repeated bites showed a shift towards the third day.


Vascular endothelial growth factor levels in the serum and synovial fluid of patients with rheumatoid arthritis.
To determine the vascular endothelial growth factor (VEGF) concentrations in serum and synovial fluid (SF) from patients with rheumatoid arthritis (RA) and to search for relationships between VEGF levels and clinical and laboratory variables. We measured VEGF levels using an enzyme-linked immunosorbent assay. Serum samples were obtained from 99 RA patients, 49 osteoarthritis (OA) patients, and 80 normal controls. Paired samples of serum and SF were collected from 32 patients with RA and 15 with OA. The mean serum VEGF concentration was 590.1 pg/ml for RA patients, 286.7 pg/ml for OA patients, and 265.8 pg/ml in controls. The serum VEGF concentration was significantly higher in the RA patients than in the OA patients or the controls (both p < 0.001). Furthermore, the VEGF levels in SF from RA patients were significantly higher than in SF from OA patients (p = 0.017). However, there was no correlation between VEGF levels in serum and SF from the same RA patients. The serum VEGF concentration was correlated with the ESR, serum CRP concentration, serum rheumatoid factor, number of tender and swollen joints, Modified Health Assessment Questionnaire, and patient and physician global assessments of disease activity in RA patients. These results suggest that VEGF level is related to RA disease activity, suggesting that VEGF may play some role in the pathogenesis of RA.


Delivery of bioactive conjugated linoleic acid with self-assembled amylose-CLA complex.
A delivery system for bioactive conjugated linoleic acid (CLA) through a self-assembled amylose-CLA complex was investigated in comparison with a beta-cyclodextrin (BCD)-CLA complex. Successful complexation between CLA and amylose or BCD was confirmed by differential scanning calorimetry, X-ray diffraction, and Fourier transform infrared spectral analysis. The yield and complexing percentages were 71.9 and 1.4% for the amylose-CLA complex and 42.3 and 7.7% for the BCD-CLA complex, respectively. However, the amylose-CLA complex showed a better antioxidative protection effect on CLA than BCD-CLA complex, supporting a strong complexing interaction between CLA and amylose shown by thermogravimetric analysis. Compared to 15.9% of CLA released from the BCD-CLA complex under simulated small intestine conditions, 95.6% of CLA was released from the amylose-CLA complex. These results indicate that an amylose-lipid complex self-assembled in the natural way of food component interaction can be used to protect and deliver functional lipids or other bioactive components into the targeted small intestine for absorption.


[Correlation of gastric cancer and effects of vitamin D receptor gene FokⅠ polymorphism on C-reactive protein and D-dimer in Uygur nationality patients].
This study aimed to determine the correlation of Uygur gastric cancer and the polymorphism effects of vitamin D receptor gene FokⅠ on C-reactive protein and D-dimer. Method of random sampling was used to select 147 Uygur patients with gastric cancer who admitted at Tumor Hospital of Xinjing Medical University (Group A) and 151 healthy controls with the same nationality (Group B). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine FokⅠ loci polymorphism in both groups to identify the gastric cancer susceptibility gene. All patients were divided into Group FF (Group a) and Group Ff+ ff (Group b) by PCR-RFLP according to the f-gene carrier to compare the expression level of C-reactive protein and D-dimer. The expression frequency of the f allelic gene of patients with gastric cancer was higher than that of healthy control patients (57.8% vs 47.4%, P<0.05). The carriers of the f allelic gene (Ff+ ff) had increased risk of gastric cancer (OR=2.85). Measurement levels of C-reactive protein and D-dimer in the f allelic gene group were higher than those of the non-f allelic gene group (4.72±1.65 vs 2.81±0.93, and 2.79±1.21 vs 1.09±0.65, respectively), and the differences were statistically significant (P<0.05). The FokⅠ loci polymorphism of vitamin D receptor gene was related to gastric cancer susceptibility in Uygur. f allelic gene may be one of the risk factors of gastric cancer in Uygur. Moreover, f allelic gene may be a factor that increased the level of C-reactive protein and D-dimer in Uygur patients with gastric cancer.


Clomipramine in the treatment of rapid (premature) ejaculation.
Twenty-three premature ejaculators (PEs) and 11 control subjects were administered 25 mg of clomipramine in a double-blind, placebo-controlled, crossover design study. During 2-week trials, subjects took either the drug or the placebo 4 to 6 hours prior to sexual activity. Daily diary data revealed that, for both groups, orgasmic latency was significantly increased when taking the clomipramine. For the PEs, the average increase in orgasmic latency during intercourse was from less than 1 minute to more than 3.5 minutes. Subjects also participated in two laboratory sessions while on the drug and placebo. During these lab sessions they were exposed to erotic videos with and without the addition of vibrotactile stimulation to the penis. Results from the laboratory data support those from the diaries. Specifically, PEs were significantly less likely to reach orgasm during the lab sessions while on the clomipramine than while on the placebo. Further, they reported a significantly greater sense of control over their orgasm while on the drug. The results of this study, along with previous research, strongly support the value of low doses of clomipramine in the treatment of premature ejaculation, specifically when taken on an as-needed basis as little as 4 hours prior to sexual activity. It is important to note, however, that the beneficial effects of the drug were not uniform across clinical subjects. In this study, those PEs with the shortest orgasmic latencies while on the placebo were the least likely to substantially improve while on the drug. Additional research is necessary to determine whether changes in the timing and dosage of the clomipramine administration can extend the benefits of the drug to those with the shortest latencies.


Induction of puberty in hypogonadal children.
Puberty is the transitional period between childhood and adulthood when physical, sexual, and psychosocial maturation occurs. The onset of puberty is controlled by the gonadotropin-releasing hormone (GnRH) neuron and is triggered when inhibition of the neuron is lifted. Subsequently, GnRH induces secretion of other hormones, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which in turn stimulate the gonads. Concurrently, increases in estrogen levels in both boys and girls stimulate growth hormone (GH) and insulin-like growth factor-I (IGF-I) secretion, which are responsible for the pubertal growth spurt. In hypogonadal children, however, hypothalamic/pituitary defects or gonadal diseases preclude the production of these hormones, preventing the onset of puberty. Hormone replacement therapy with either estrogen or testosterone is a viable treatment option for hypogonadal children. These should be administered with consideration of sexual maturation rates, statural and bone growth rates, and occurrence of adverse effects. The merits and disadvantages of various hormone replacement therapies for girls and for boys are discussed.


Efficacy of recombinant human follicle-stimulating hormone in improving oocyte quality in assisted reproductive techniques.
To estimate the efficacy of recombinant human follicle-stimulating hormone (rFSH) versus highly purified urinary human FSH (uFSH) in women undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET). This prospective, randomized, quality of retrieved double-blind study compared uFSH with rFSH in IVF-ET rFSh cycles. A total of 254 cycles from 241 patients who attended the infertility clinic at Samsung Cheil Hospital from January to August 2001 were included in the study. With pituitary desensitization using gonadotropin-releasing hormone agonist and a short protocol, rFSH was administered in 131 cycles; uFSH was administered in 123 cycles. We analyzed ovarian response, oocyte quality, fertilization rate, embryo quality, pregnancy rate and live birth rate in the uFSH and rFSH groups. Total FSH dosage (1322.3 +/- 526.2 vs. 2124.4 +/- 881.9 i.u.) and dosage per retrieved oocyte (90.6 +/- 36.0 vs. 138.0 +/- 57.2 i.u.) were significantly lower in the rFSH group than those in the uFSH group (P < .001). The proportion of good-quality oocytes (grade 1 and 2) was higher in the rFSH group (68.2% vs. 64.8%, P = .024). Moreover, the proportion of atretic oocytes (grade 5) was lower in the rFSH group (7.5% vs. 10.3%, P = .002). The fertilization rate, quality of transferred embryos, clinical pregnancy rate and live birth rate were not significantly differ between the 2 groups. In women undergoing COH, rFSH revealed more efficient ovarian response and better quality of oocytes than did uFSH.


Ruthenium nanocatalysis on redox reactions.
Nanoparticles have generated intense interest over the past 20 years due to their high potential applications in different areas such as catalysis, sensors, nanoscale electronics, fuel and solar cells and optoelectronics. As the large fractions of metal atoms are exposed to the surface, the use of metal nanoparticles as nanocatalysts allows mild reaction conditions and high catalytic efficiency in a large number of chemical transformations. They have emerged as sustainable heterogeneous catalysts and catalyst supports alternative to conventional materials. This review focuses on the synthesis, characterization and catalytic role of ruthenium nanoparticles (RuNPs) on the redox reactions of heteroatom containing organic compounds with the green reagent H2O2, a field that has attracted immense interest among the chemical, materials and industrial communities. We intend to present a broad overview of Ru nanocatalysts for redox reactions with an emphasis on their performance, stability and reusability. The growth in the chemistry of organic sulfoxides and N-oxides during last decade was due to their importance as synthetic intermediates for the production of a wide range of chemically and biologically active molecules. Thus design of efficient methods for the synthesis of sulfoxides and N-oxides becomes important. This review concentrates on the catalysis of RuNPs on the H2O2 oxidation of organic sulfides to sulfoxides and amines to N-oxides. The deoxygenation reactions of sulfoxides to sulfides and reduction of nitro compounds to amines are fundamental reactions in both chemistry and biology. Here, we also highlight the catalysis of metal nanoparticles on the deoxygenation of sulfoxides and sulfones and reduction of nitro compounds with particular emphasis on the mechanistic aspects.


T lymphocyte proliferative capacity and CD4+/CD8+ ratio in primiparous and pluriparous lactating cows.
T cells play a central role in specific immunity; their populations and phenotypes could be affected by number of lactation in high-yielding dairy cows. To investigate the effects of parity on the dynamics of T lymphocytes, lymphoproliferative capacity, T lymphocyte subsets and CD4+/CD8+ ratio were studied in peripheral blood of primiparous and pluriparous dairy cows during mid-late lactation. A non-radioactive technique was also adapted for a detailed lymphoproliferation assay. Compared with the primiparous cows, the pluriparous cows exhibited weaker lymphoproliferative activity, larger number of CD4+ cells and substantially greater CD4+/CD8+ ratio in their blood circulation. The increase of the CD4+/CD8+ ratio in the blood of pluriparous dairy cows was mainly due to the rise in the proportion of CD4+ cells and decline in the proportion of CD8+ cells. This increase of the CD4+/CD8+ ratio coincided with the decrease of mitogen-induced proliferation capacity of T lymphocytes. Of four lymphocyte divisions or generations during the lymphoproliferation assay, maximal lymphocyte proliferation capacity at generation 3 in primiparous cows was markedly greater than in pluriparous cows. With an alternatively safer, faster and more reproducible assay (compared with 3H-thymidine scintillation assay) we showed for the first time that aging in dairy cows leads to a decreased mitogen-induced lymphoproliferation and disturbed proportion between CD4+ and CD8+ T cells. This CD4+-CD8+ imbalance together with diminished lymphoproliferative capacity may lead to a weaker T cytotoxic-mediated immunity and increased susceptibility to infectious diseases in pluriparous lactating cows. Our study also emphasizes further application of the methods in farm animals.


Potential mechanism for pentachlorophenol-induced carcinogenicity: a novel mechanism for metal-independent production of hydroxyl radicals.
The hydroxyl radical ((*)OH) has been considered to be one of the most reactive oxygen species produced in biological systems. It has been shown that (*)OH can cause DNA, protein, and lipid oxidation. One of the most widely accepted mechanisms for (*)OH production is through the transition metal-catalyzed Fenton reaction. Pentachlorophenol (PCP) was one of the most widely used biocides, primarily for wood preservation. PCP is now ubiquitously present in our environment and even found in people who are not occupationally exposed to it. PCP has been listed as a priority pollutant by the U.S. Environmental Protection Agency (EPA) and classified as a group 2B environmental carcinogen by the International Association for Research on Cancer (IARC). The genotoxicity of PCP has been attributed to its two major quinoid metabolites: tetrachlorohydroquinone and tetrachloro-1,4-benzoquinone (TCBQ). Although the redox cycling of PCP quinoid metabolites to generate reactive oxygen species is believed to play an important role, the exact molecular mechanism underlying PCP genotoxicity is not clear. Using the salicylate hydroxylation assay and electron spin resonance (ESR) secondary spin-trapping methods, we found that (*)OH can be produced by TCBQ and H(2)O(2) independent of transition metal ions. Further studies showed that TCBQ, but not its corresponding semiquinone radical, the tetrachlorosemiquinone radical (TCSQ(*)), is essential for (*)OH production. The major reaction product between TCBQ and H(2)O(2) was identified to be trichloro-hydroxy-1,4-benzoquinone (TrCBQ-OH), and H(2)O(2) was found to be the source and origin of the oxygen atom inserted into this reaction product. On the basis of these data, we propose that (*)OH production by TCBQ and H(2)O(2) is not through a semiquinone-dependent organic Fenton reaction but rather through the following novel mechanism: a nucleophilic attack of H(2)O(2) to TCBQ, leading to the formation of an unstable trichloro-hydroperoxyl-1,4-benzoquinone (TrCBQ-OOH) intermediate, which decomposes homolytically to produce (*)OH. These findings represent a novel mechanism of (*)OH formation not requiring the involvement of redox-active transition metal ions and may partly explain the potential carcinogenicity of the widely used biocides such as PCP and other polyhalogenated aromatic compounds.