Histology of skeletal muscle reconstructed by means of the implantation of autologous adipose tissue: an experimental study.
The purpose of this study was to determine the histological characteristics of a skeletal muscle reconstructed by means of the implantation of autologous adipose tissue following an experimentally-induced volumetric muscle loss. A cylindrical piece in the belly of the rat anterior tibial muscle was removed. In the hole, inguinal subcutaneous adipose tissue of the same rat was grafted. Animals were sacrificed 7, 14, 21, 28 and 60 days posttransplantation. Histological, histochemical, immunohistochemical and morphometric techniques were used. At all times analyzed, the regenerative muscle fibers formed from the edges of the muscle tissue showed histological, histochemical and immunohistochemical differences in comparison with the control group. These differences are related to delays in the maturation process and are related to problems in reinnervation and disorientation of muscle fibers. The stains for MyoD and desmin showed that some myoblasts and myotubes seem to derive from the transplanted adipose tissue. After 60 days, the transplant area was 20% occupied by fibrosis and by 80% skeletal muscle. However, the neo-muscle was chaotically organized showing muscle fiber disorientation and centronucleated fibers with irregular shape and size. Our results support the hypothesis that, at least from a morphological point of view, autologous adipose tissue transplantation favors reconstruction following a volumetric loss of skeletal muscle by combining the inherent regenerative response of the organ itself and the myogenic differentiation of the stem cells present in the adipose tissue. However, in our study, the formed neo-muscle exhibited histological differences in comparison with the normal skeletal muscle.


Design, development, and characterization of lipid nanocarriers-based epigallocatechin gallate delivery system for preventive and therapeutic supplementation.
Green tea is manufactured from the leaves of Camellia sinensis and has been shown to possess, among other properties, anticancer, antiobesity, antiatherosclerotic, antidiabetic, antibacterial, and antiviral effects. The beneficial effects of green tea are related to the activities of (-)-epigallocatechin gallate (EGCG). This catechin is very unstable, undergoing degradation and epimerization, which is responsible for the loss of its health benefits. Encapsulation in nanoparticles (NPs) is an effective method to protect EGCG from adverse environmental conditions. In this work, solid lipid NPs (SLN) and nanostructured lipid carriers (NLC) were successfully developed to be used as biocompatible nanocarriers, enhancing the stability of EGCG. The mean diameter of the NPs was found to be around 300-400 nm, which is suitable for oral administration. Moreover, EGCG was effectively encapsulated with a remarkable efficiency of encapsulation of 80% and 90% for SLN and NLC, respectively. In addition, high storage stability of the formulations is expected as they maintain the initial characteristics for 3 months. Limited release of EGCG from the NPs was observed in simulated gastric and intestinal fluids. MTT and lactate dehydrogenase (LDH) assays demonstrated that NPs possess low toxicity, and so have potential to be used for preventive and therapeutic EGCG supplementation.


Determination of DNA damage in floriculturists exposed to mixtures of pesticides.
The aim of the study was to determine possible DNA damage in floriculturists chronically exposed to pesticides. Leukocytes from 52 workers, 46 environmentally exposed, and 38 control individuals were evaluated with the comet assay. Serum from all individuals was also analyzed for pesticides using gas chromatography coupled to mass spectrometry. A statistically significant difference in DNA fragmentation in the pesticide exposed group compared to the other two groups (P < .001) was found. No differences between environmentally exposed and control individuals were detected. The statistical analysis showed no significant correlation between DNA damage and sex, age, drinking or smoking habits, as well as years of exposure. One or more pesticides were detected in 50% of the floriculturists, while in the rest of the individuals, a chemical related with the preparation of pesticides, such as additives, plasticizers, or solvents, was found. Our study shows that chronic exposure to pesticides produces DNA damage in floriculturists. It also suggests that this type of monitoring could be valuable in recommending preventive measures.


Real-world treatment patterns and survival for locally advanced esophageal squamous cell carcinoma.
The "real world" treatment mode and clinical efficacy of locally advanced esophageal squamous cell carcinoma (LAESCC) are unclear. Meanwhile, the role of immunotherapy in the clinical practice is also puzzling. We conducted the research to investigate the statue of "real world" LAESCC. The clinical data of patients with locally advanced esophageal squamous cell carcinoma which met the criteria from January 2010 to December 2019 have been retrospectively analyzed, and the distribution of clinical treatment patterns has been analyzed. They cover such aspects as dfferences in survival time and further analysis of the differences in overall survival (OS) and progression-free survival (PFS) between patients who received immunotherapy and those who did not receive immunotherapy. What is more, Cox risk regression model has also been used to evaluate the risk factors affecting the prognosis of LAESCC. The cases of a total of 5328 newly diagnosed patients with esophageal cancer were collected, and a total of 363 patients were included in the study, with a median age of (46.2 ± 7.8) years old; 84 (23.1%) and 279 (76.9%) patients received 1L and ≥ 2L, respectively; Concurrent chemoradiotherapy (74.1%) and paclitaxel combined with platinum-based chemotherapy (14.3%) were the main first-line treatment options; fluorouracil combined with cisplatin regimen-based chemotherapy (63.8%) was the main treatment option for ≥ 2L, of which 69 patients (25.3%) received immunization treatment; OS of patients with 1 line of therapy and ≥ 2L were (22.4 ± 7.2) months and (38.7 ± 8.5) months, respectively, and the comparison between groups was statistically significant (P < .05); among 69 patients with ≥ 2L who received immunotherapy, PFS and The OS was (14.6 ± 6.9) and (45.3 ± 9.7) respectively, and the comparison between the groups was statistically significant (all P < .05). Cox multivariate analysis has shown that clinical stage, immunotherapy, concurrent chemoradiotherapy, and ≥ 2L are the main factors affecting OS. and immunotherapy, concurrent chemoradiotherapy, and ≥ 2L are independent factors affecting PFS. Concurrent chemoradiotherapy is currently one of the standard treatments for LAESCC, and most patients are still willing to receive second-line or above treatments. Adding immunotherapy to standard treatment modalities may further optimize clinical treatment modalities and improve patient outcomes.


Surviving sepsis campaign: a critical reappraisal.
In 2002, the declaration of Barcelona launched a worldwide campaign that proposed to decrease in sepsis-related mortality by the introduction of evidence-based medicine into the management of sepsis. This paved the way for the publication of a wide selection of recommendations entitled the Surviving Sepsis Campaign (SSC) Guidelines. Whereas most of the medical community received the guidelines with enthusiasm, dissonant voices were made public just after its publication, and in recent years, the SSC guidelines were a source of intense debate, resulting in a recent revision of the guidelines. In the midst of a large controversy, it is evident that a critical reappraisal of the SSC guidelines is timely. In our opinion, whereas many relevant aspects of the SSC guidelines have been discussed, there are three major limitations that deserve a closer look, and they are sepsis as a public health issue, the weight of the evidence behind the recommendations, and the absence of recommendations related to the prevention of sepsis. In conclusion, although we recognize that the SSC is a valuable initiative, many of its present aspects must be revised to provide a clear message for clinicians taking care of sepsis patients at bedside. New guidelines should be based on solid evidence, have no interference from the pharmaceutical or medical equipment industry, and should have a stronger preventive and public health approach.


Assessment of human islet labeling with clinical grade iron nanoparticles prior to transplantation for graft monitoring by MRI.
Ex vivo labeling of islets with superparamagnetic iron oxide (SPIO) nanoparticles allows posttransplant MRI imaging of the graft. In the present study, we compare two clinical grade SPIOs (ferucarbotran and ferumoxide) in terms of toxicity, islet cellular uptake, and MRI imaging. Human islets (80-90% purity) were incubated for 24 h with various concentrations of SPIOs (14-280 μg/ml of iron). Static incubations were performed, comparing insulin response to basal (2.8 mM) or high glucose stimulation (16.7 mM), with or without cAMP stimulation. Insulin and Perl's (assessment of iron content) staining were performed. Electronic microscopy analysis was performed. Labeled islets were used for in vitro or in vivo imaging in MRI 1.5T. Liver section after organ removal was performed in the same plane as MRI imaging to get a correlation between histology and radiology. Postlabeling islet viability (80 ± 10%) and function (in vitro static incubation and in vivo engraftment of human islets in nude mice) were similar in both groups. Iron uptake assessed by electron microscopy showed iron inclusions within the islets with ferucarbotran, but not with ferumoxide. MRI imaging (1.5T) of phantoms and of human islets transplanted in rats, demonstrated a strong signal with ferucarbotran, but only a weak signal with ferumoxide. Signal persisted for >8 weeks in the absence of rejection. An excellent correlation was observed between radiologic images and histology. The hepatic clearance of intraportally injected ferucarbotran was faster than that of ferumoxide, generating less background. A rapid signal decrease was observed in rejecting xenogeneic islets. According to the present data, ferucarbotran is the most appropriate of available clinical grade SPIOs for human islet imaging.


Mucoid impaction: a localized form of allergic bronchopulmonary aspergillosis.
Mucoid impaction is defined as the obstruction of proximal bronchi by mucous plugs and exudates. There are striking similarities between patients with mucoid impaction and those with allergic bronchopulmonary aspergillosis (ABPA), often referred to as "mucoid microimpaction." We evaluated three patients with mucoid impaction for diagnostic criteria of ABPA and human leukocyte antigen type. We found that certain human leukocyte antigen types were common among mucoid impaction patients and those with ABPA. It is possible that patients with mucoid impaction could represent a localized form of ABPA.


Beneficial effects of a woman-focused development programme on child survival: evidence from rural Bangladesh.
This paper reports results from a prospective study of the impact of a woman-focused development programme on child survival in Matlab, a rural area of Bangladesh. The programme was targeted to households owning less than 50 decimals of land and members selling more than 100 days of labour for living in a year. Programme components included formation of women's groups for saving and credit, training on skill development, functional literacy including legal and social awareness, and technical and marketing support to projects undertaken with the loan money from the organization. A total of 13,549 children born alive during 1988-97 in the study area were included in the study. Hazards of mortality during pre- and post-intervention periods were compared among the programme participants and non-participants controlling the effects of other relevant variables. There has been a substantial reduction in mortality during the post-intervention period; however, the reduction was much greater for infants whose mothers participated in the development programme compared to infants of non-participant mothers from similar socioeconomic background. In a relative sense, there has been a 52% reduction of the pre-intervention level hazard of death of children during infancy of participant mothers compared to 31% reduction for the infants of non-participant mothers from similar socioeconomic background. There had also been a substantial reduction in hazard of death during childhood (1-4 year age group), however, the reduction was statistically similar for all groups of children irrespective of their mothers' participation in the development programmes.


Temperature modulation of integrin-mediated cell adhesion.
In response to external stimuli, cells modulate their adhesive state by regulating the number and intrinsic affinity of receptor/ligand bonds. A number of studies have shown that cell adhesion is dramatically reduced at room or lower temperatures as compared with physiological temperature. However, the underlying mechanism that modulates adhesion is still unclear. Here, we investigated the adhesion of the monocytic cell line THP-1 to a surface coated with intercellular adhesion molecule-1 (ICAM-1) as a function of temperature. THP-1 cells express the integrin lymphocyte function-associated antigen-1 (LFA-1), a receptor for ICAM-1. Direct force measurements of cell adhesion and cell elasticity were carried out by atomic force microscopy. Force measurements revealed an increase of the work of de-adhesion with temperature that was coupled to a gradual decrease in cellular stiffness. Of interest, single-molecule measurements revealed that the rupture force of the LFA-1/ICAM-1 complex decreased with temperature. A detailed analysis of the force curves indicated that temperature-modulated cell adhesion was mainly due to the enhanced ability of cells to deform and to form a greater number of longer membrane tethers at physiological temperatures. Together, these results emphasize the importance of cell mechanics and membrane-cytoskeleton interaction on the modulation of cell adhesion.


Pulmonary mechanics in healthy term neonates: variability in measurements obtained with a computerized system.
Using a commercially available computer-based analysis of ventilation and esophageal pressure (PeDs), we studied 11 healthy term neonates with serial pulmonary mechanics measurements during the first 3 days of life to determine the intrasubject variability of repeated measurements. Three consecutive pulmonary function tests were obtained before and after repositioning of the esophageal catheter, for a total of six measurements per day in each subject. The daily coefficient of variation for these 11 subjects ranged from 6% to 32% for respiratory rate; 6% to 27% for tidal volume; 3% to 28% for specific dynamic compliance, and 11% to 69% for pulmonary resistance. Repositioning the esophageal catheter did not produce significant differences in measurements of pulmonary mechanics (p greater than 0.05). We conclude that within a given subject, the maximum variability (mean + 2 SD) was 28% for specific dynamic compliance and 56% for pulmonary resistance. These intrasubject variability limits are important when one is interpreting pulmonary mechanics measurements in neonates before and after specific treatment, such as bronchodilators, diuretics, surfactant, or steroids.


PTEN expression is consistent in colorectal cancer primaries and metastases and associates with patient survival.
Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) negatively regulates the phosphoinositide-3-kinase (PI3K) signaling pathway. In colorectal cancer (CRC), observed frequencies of loss of PTEN expression, concordant expression in primary tumors and metastases, and the association of PTEN status with outcome vary markedly by detection method. We determined the degree to which PTEN expression is consistent in 70 matched human CRC primaries and liver metastases using a validated immunohistochemistry assay. We found loss of PTEN expression in 12.3% of assessable CRC primaries and 10.3% of assessable liver metastases. PTEN expression (positive or negative) was concordant in 98% of matched colorectal primaries and liver metastases. Next we related PTEN status to mutations in RAS and PI3K pathway genes (KRAS, NRAS, BRAF , and PIK3CA) and to overall survival (OS). PTEN expression was not significantly associated with the presence or absence of mutations in RAS or PI3K pathway genes. The median OS of patients whose tumors did not express PTEN was 9 months, compared to 49 months for patients whose tumors did express PTEN (HR = 6.25, 95% confidence intervals (CI) (1.98, 15.42), P = 0.0017). The association of absent PTEN expression with increased risk of death remained significant in multivariate analysis (HR = 6.31, 95% CI (2.03, 17.93), P = 0.0023). In summary, PTEN expression was consistent in matched CRC primaries and in liver metastases. Therefore, future investigations of PTEN in metastatic CRC can use primary tumor tissue. In patients with liver-only metastases, loss of PTEN expression predicted poor OS.


[Relationship between the dietary behavior targets of Health Japan 21 (second term) and perceived food environment and health literacy].
Objective The interim evaluation of Health Japan 21(second term), a national health promotion plan, suggested that improvements in the food environment did not lead to improvements in individual dietary habits. The present study aimed to evaluate the relationship between the dietary behavior targets of Health Japan 21 (second term) and perceived food environment and health literacy.Method We conducted an online cross-sectional survey in March 2019 among adults aged 20-64 years. From the 9,667 registered monitors of the research firm, we collected 2,851 responses (29.5% response rate). The perceived food environment (how people perceive the local food environment) was estimated using the following six questions, namely, availability: easy access to nutritionally balanced meals, accessibility: no inconvenience in daily shopping, affordability: access to nutritionally balanced meals at reasonable prices, accommodation: easy access to food services within business hours, acceptability: satisfaction with the quality of food ingredients, and another form of acceptability: adequate food safety. Health literacy was evaluated using five questions related to information gathering, information selection, information transfer, information judgment, and self-determination. Last, we asked the respondents about two dietary behaviors, namely, the frequency of a balanced diet (defined as comprising the staple food, a main dish, and a side dish) and the quantity of vegetable intake, along with sociodemographic information. The analysis included 2,111 respondents, excluding those whose socioeconomic status was unknown. Multiple logistic regression analyses were performed to determine the relationship between perceived food environment and health literacy on dietary behaviors, while adjusting for sociodemographic factors.Result A balanced diet was associated with the following perceptions of the food environment: "access to nutritionally balanced meals at reasonable prices" (adjusted odds ratio [95% confidence interval] = 1.37 [1.02, 1.82]; women), and "adequate food safety" (1.54 [1.19, 1.98]; men), and health literacy: "information gathering" (0.84 [0.73,0.97]; men) and "self-determination" (1.28 [1.10,1.50], 1.37 [1.14,1.63]; men, women). The quantity of vegetable intake was associated with the following perceptions of the food environment: "easy access to nutritionally balanced meals" (1.54 [1.15,2.06]; men), and "no inconvenience in daily shopping" (1.55 [1.12,2.15]; women), and health literacy: "information transfer" (1.30 [1.10,1.54]; men), and "self-determination" (1.67 [1.38,2.02]; women)).Conclusion To achieve a balanced diet and increased vegetable intake in a population, it is necessary to promote both the acquisition of a higher level of "self-determination" (rather than "information gathering") in health literacy and the creation of a heathy food environment.


Are elderly end-stage renal disease patients more susceptible for drug resistant organisms in their sputum?
End stage renal disease (ESRD) patients are at risk for pneumonia in view of their impaired immune status. Similar empiric antibiotic regimens are used in elderly as well as young ESRD patients with respiratory tract infections. We conducted an observational, cross sectional study between June 2007 and June 2008 in 100 ESRD patients half being > 65 yrs. All patients had positive sputum culture and chest X-ray findings of pneumonia Streptococcus pneumoniae was the commonest in younger while Klebsiella pneumoniae in > 65 yrs old patients. Elderly patients had significant resistance to common antibiotics. Ceftrioxone was the most suitable antibiotic in the younger patients while a combination of piperacillin with gentamycin was the best choice in the geriatric age group. In conclusion, organisms cultured from sputum in ESRD patients with pneumonia were different in the ESRD patients of more than and less than 65 years of age as well as the drug susceptibility. We should probably redefine the management of pneumonia according to the sensitivities in our local populations to better treat these patients.


Studies of renal injury III: lipid-induced nephropathy in type II diabetes.
Studies of renal injury III: Lipid-induced nephropathy in type II diabetes. Nephrotoxicity from elevated circulating lipids occurs in experimental and clinical situations. We tested the hypothesis that lipid-induced nephropathy causes advanced renal failure in rats with type II diabetes and dyslipidemia. First generation (F1) hybrid rats derived from the spontaneous hypertensive heart failure rat (SHHF/Gmi-fa) and the LA/NIH-corpulent rat (LA/N-fa) were studied for 41 weeks while being on specific diets. Group 1 (14 rats) ingested 11.5% protein, 47.9% fat, and 40.6% carbohydrate. Group 2 (8 rats) ingested 26.9% protein, 16.7% animal fat, and 56.4% carbohydrate, and group 3 (20 rats) ingested 20.2% protein, 40.4% soy and coconut oil, and 39.4% carbohydrate. Hyperglycemia was more severe in rat groups 1 and 2 than in group 3. In contrast, circulating cholesterol and hydroperoxide levels were highest in group 3, intermediate in group 2, and lowest in group 1. Group 3 had severe renal failure secondary to glomerulosclerosis and tubulointerstitial disease, with striking deposition of the lipid peroxidation stress biomarker 4-hydroxynonenal in glomeruli and renal microvessels. Moreover, in group 3, increased arterial wall thickness also connoted vascular injury. In contrast, the glycoxidation stress biomarkers pentosidine and carboxymethyl-lysine were preferentially localized to renal tubules of hyperglycemic rats in groups 1 and 2 and did not segregate with the most severe renal injury. Glomerular and interstitial fibrosis was accompanied by proportional increases in renal transforming growth factor-beta1 levels, which were threefold higher in the hypercholesterolemic rats of group 3 than in the hyperglycemic rats of group 1. Acquisition of non-nodular glomerular sclerosis and tubulointerstitial disease is dependent on lipoxidation stress in rats with type II diabetes. On the other hand, in the absence of hypercholesterolemia, prolonged glycoxidation stress does not appear to be uniquely nephrotoxic.


[Influence of electroacupuncture intervention on free radical metabolism in athletes undergoing intensive endurance exercise].
To observe the effect of electroacupuncture (EA) intervention on free radical metabolism in athletes during intensive endurance exercise, so as to reveal its mechanism underlying fatigue relief. Thirty male college student volunteers were equally divided into control group, intensive endurance exercise group (exercise group for short) and EA group. Student volunteers in both exercise and EA groups were asked to conduct fixed quantitative load exercise (Harvard step test) for 30 min, once daily for 15 days. EA was applied to bilateral Xuehai (SP 10), Zusanli (ST36), Taichong (LR3), and Sanyinjiao (SP 6) for 30 min, once daily for 15 days. Serum malondialdehyde (MDA) contents and superoxide dismutase (SOD) activity levels on the day before exercise, one day after exercise and 15 days after EA intervention were detected by using thiomalonylurea colorimetric method and xanthine oxidase method, respectively. Compared with pre-exercise or the control group, serum MDA content and SOD activity after one day's intensive endurance exercise were increased significantly in both exercise and EA groups (P < 0.05, P < 0.01), and the ratios of SOD/MDA decreased considerably in the latter two groups (P < 0.01). At the time-point of post-EA intervention, serum MDA level was significantly higher in the exercise group than in the control group (P < 0.05), serum MDA content in the EA group was significantly lower than that in the exercise group (P < 0.05), and serum SOD activity in the EA group was significantly higher than that in the exercise group (P < 0.01). The ratio of SOD/ MDA was increased obviously in the EA group than in the exercise group (P < 0.01). EA can decrease serum MDA content and increase SOD activity and SOD/MDA in athletes experiencing intensive endurance exercise, which may contribute to its effect in relieving athletic fatigue.


The pathway of in-situ ammonium removal from aerated municipal solid waste bioreactor: nitrification/denitrification or air stripping?
In-situ ammonium removal from municipal solid waste (MSW) landfill is an attractive method due to its economic advantages. In this study, two simulated MSW bioreactors with different degrees of initial bio-stabilization were utilized to investigate the effects of intermittent aeration mode and the addition of activated sludge on the removal of ammonium. The results showed that up to 90% of ammonium could be removed and the amount of NO(x)-N produced was less than 1% of NH4 (+)-N removed in both reactors. The pH values increased rapidly and finally arrived at a high level of 8.5-8.8. The efficiency of ammonium removal was improved by increasing the continuous aeration time, but it was not affected by the addition of activated sludge. A portion of liquid escaped from the reactors in the form of vapour, and as high as 195-258 mg L(-1) of NH(4) ( +)-N was detected in the vapour collector. According to calculation, nitrification was inhibited by the high level of free ammonia in the bioreactors. As a result, air stripping was enhanced and became the primary pathway of ammonium removal. Therefore, controlling free ammonia concentration was essential in ammonium removal from the aerated MSW bioreactor.


Fourier X-ray scattering radiography yields bone structural information.
To characterize certain aspects of the microscopic structures of cortical and trabecular bone by using Fourier x-ray scattering imaging. Protocols approved by the National Institutes of Health Animal Care and Use Committee were used to examine ex vivo the hind limb of a rat and the toe of a pig. The Fourier x-ray scattering imaging technique involves the use of a grid mask to modulate the cone beam and Fourier spectral filters to isolate the harmonic images. The technique yields attenuation, scattering, and phase-contrast (PC) images from a single exposure. In the rat tibia cortical bone, the scattering signals from two orthogonal grid orientations were compared by using Wilcoxon signed rank tests. In the pig toe, the heterogeneity of scattering and PC signals was compared between trabecular and compact bone regions of uniform attenuation by using F tests. In cortical bone, the scattering signal was significantly higher (P < 10(-15)) when the grid was parallel to the periosteal surface. Trabecular bone, as compared with cortical bone, appeared highly heterogeneous on the scattering (P < 10(-34)) and PC (P < 10(-27)) images. The ordered alignment of the mineralized collagen fibrils in compact bone was reflected in the anisotropic scattering signal in this bone. In trabecular bone, the porosity of the mineralized matrix accounted for the granular pattern seen on the scattering and PC images.


Transmembrane topography of the 100-kDa a subunit (Vph1p) of the yeast vacuolar proton-translocating ATPase.
The membrane topography of the yeast vacuolar proton-translocating ATPase a subunit (Vph1p) has been investigated using cysteine-scanning mutagenesis. A Cys-less form of Vph1p lacking the seven endogenous cysteines was constructed and shown to have 80% of wild type activity. Single cysteine residues were introduced at 13 sites within the Cys-less mutant, with 12 mutants showing greater than 70% of wild type activity. To evaluate their disposition with respect to the membrane, vacuoles were treated in the presence or absence of the impermeant sulfhydryl reagent 4-acetamido-4'-maleimidylstilbene-2,2'-disulfonic acid (AMS) followed by the membrane permeable sulfhydryl reagent 3-(N-maleimidylpropionyl) biocytin (MPB). Three of the 12 active cysteine mutants were not labeled by MPB. The mutants E3C, D89C, T161C, S266C, N447C, K450C, and S703C were labeled by MPB in an AMS-protectable manner, suggesting a cytoplasmic orientation, whereas G602C and S840C showed minimal protection by AMS, suggesting a lumenal orientation. Factor Xa cleavage sites were introduced at His-499, Leu-560, and Pro-606. Cleavage at 560 was observed in the absence of detergent, suggesting a cytoplasmic orientation for this site. Based on these results, we propose a model of the a subunit containing nine transmembrane segments, with the amino terminus facing the cytoplasm and the carboxyl terminus facing the lumen.


[Medical indications for laser therapy in dermatology].
Laser therapy in dermatology is often associated with cosmetic procedures. However, nowadays laser therapy has become a treatment modality for many dermatological diseases. We present three cases of patients with different dermatological diseases that are highly therapy-resistant. The first case is a 19-year-old man with multiple angiofibromas in the face, who was treated with ablative laser therapy. We also administered ablative laser therapy to a 64-year-old man with a big tumourous nose due to granuloma faciale, who had already tried multiple treatment options without result. Finally, a 69-year-old woman with extensive neurofibromas in the face, which had been considered untreatable, was successfully treated with ablative laser therapy. We would like to show the extensive therapeutical options of laser therapy for difficult-to-treat dermatological diseases.


N-acetylcysteine negatively regulates Notch3 and its malignant signaling.
Notch3 receptor is expressed in a variety of cancers and the excised active intracellular domain (N3ICD) initiates its signaling cascade. N-acetylcysteine (NAC) as an antioxidant has been implicated in cancer prevention and therapy. In this study, we demonstrated a negative regulation of Notch3 by NAC in cancer cells. HeLa cells treated with NAC exhibited a time- and concentration-dependent decrease in Notch3 levels and its downstream effectors Hes1 and HRT1 in a manner independent of f-secretase or glutathione. In contrast, NAC did not affect protein levels of Notch1, the full length Notch3 precursor, or ectopically expressed N3ICD. Although SOD, catalase and NAC suppressed reactive oxygen species in HeLa cells, the first two antioxidants did not impact on Notch3 levels. While the mRNA expression of Notch3 was not altered by NAC, functional inhibition of lysosome, but not proteasome, blocked the NAC-dependent reduction of Notch3 levels. Furthermore, results from Notch3 silencing and N3ICD overexpression demonstrated that NAC prevented malignant phenotypes through down-regulation of Notch3 protein in multiple cancer cells. In summary, NAC reduces Notch3 levels through lysosome-dependent protein degradation, thereby negatively regulates Notch3 malignant signaling in cancer cells. These results implicate a novel NAC treatment in sensitizing Notch3-expressing tumors.


Sharing and Reuse of Sensitive Data and Samples: Supporting Researchers in Identifying Ethical and Legal Requirements.
Availability of and access to data and biosamples are essential in medical and translational research, where their reuse and repurposing by the wider research community can maximize their value and accelerate discovery. However, sharing human-related data or samples is complicated by ethical, legal, and social sensitivities. The specific ethical and legal requirements linked to sensitive data are often unfamiliar to life science researchers who, faced with vast amounts of complex, fragmented, and sometimes even contradictory information, may not feel competent to navigate through it. In this case, the impulse may be not to share the data in order to safeguard against unintentional misuse. Consequently, helping data providers to identify relevant ethical and legal requirements and how they might address them is an essential and frequently neglected step in removing possible hurdles to data and sample sharing in the life sciences. Here, we describe the complex regulatory context and discuss relevant online tools-one which the authors co-developed-targeted at assisting providers of sensitive data or biosamples with ethical and legal questions. The main results are (1) that the different approaches of the tools assume different user needs and prior knowledge of ethical and legal requirements, affecting how a service is designed and its usefulness, (2) that there is much potential for collaboration between tool providers, and (3) that enriched annotations of services (e.g., update status, completeness of information, and disclaimers) would increase their value and facilitate quick assessment by users. Further, there is still work to do with respect to providing researchers using sensitive data or samples with truly 'useful' tools that do not require pre-existing, in-depth knowledge of legal and ethical requirements or time to delve into the details. Ultimately, separate resources, maintained by experts familiar with the respective fields of research, may be needed while-in the longer term-harmonization and increase in ease of use will be very desirable.


Cor triatriatum and coronary artery fistula in tetralogy of Fallot.
Coexistence of divided left atrium with tetralogy of Fallot is rare. Preoperative diagnosis of this rare association is difficult. We here report preoperative diagnosis of this rare combination. In addition, the patient also had coronary to left ventricle fistula.


Influence of vitamin D status on the content of complexed acidic phospholipids in chick diaphyseal bone.
Calcium acidic phospholipid phosphate complexes cause hydroxyapatite formation in vitro and in vivo. Previous studies have shown that the amount of these complexed acidic phospholipids is altered in the bones of animals depleted of vitamin D and phosphate. To help differentiate the effects of vitamin D from those due to altered mineral metabolism, the amount of complexed acidic phospholipids present in diaphyseal bone was determined in five groups of chicks varying in calcium, phosphate and vitamin D status. Highest levels of complexed acidic phospholipids were found in chicks receiving vitamin D and having normal serum levels of Ca and P. Lowest levels were found in vitamin D-deficient chicks; levels were not altered in vitamin D-deficient chicks when their serum Ca was normalized. Intermediate levels were found in vitamin D-treated chicks fed a low Ca diet. Levels of the complexed acidic phospholipids were low in bones of hypophosphatemic, vitamin D-treated chicks but, when related to total lipid phosphorus content, values were similar to those of hypocalcemic chicks. These data suggest that while disturbances in calcium and phosphate metabolism which are present in rickets influence the bone content of these complexed acidic phospholipids, vitamin D may also play a direct role in their formation. Further, the ability of vitamin D to increase bone complexed acidic phospholipid content does not seem to be related to its hypercalcemic effect.


Relationship between alpha adrenoceptor occupancy and response for the alpha-1 adrenoceptor agonist, cirazoline, and the alpha-2 adrenoceptor agonist, B-HT 933, in canine saphenous vein.
The relationship between alpha adrenoceptor occupancy and response was investigated for the alpha-1 adrenoceptor agonist, cirazoline, and the alpha-2 adrenoceptor agonist, B-HT 933, in canine saphenous vein, a tissue known to contain both alpha adrenoceptor subtypes. Both cirazoline and B-HT 933 produced dose-dependent vasoconstrictor responses in canine saphenous vein, with the maximum vasoconstrictor response elicited by B-HT 933 being only 75% of that produced by cirazoline. Dissociation constants were obtained for cirazoline (0.61 microM) and B-HT 933 (4.99 microM) for interaction with postsynaptic vascular alpha-1 and alpha-2 adrenoceptors, respectively, by the method of fractional irreversible receptor inactivation using phenoxybenzamine. Based on this information, alpha-1 and alpha-2 adrenoceptor occupancy-response relationships were constructed. The alpha-1 adrenoceptor occupancy-response relationship obtained for cirazoline was approximately 4-fold more favorable than the alpha-2 adrenoceptor occupancy-response relationship for B-HT 933, although both agonists were associated with a significant receptor reserve. The alpha-1 adrenoceptor occupancy-response relationship of cirazoline and the alpha-2 adrenoceptor occupancy-response relationship of B-HT 933 were both rectangular hyperbolas, suggesting that both compounds have high intrinsic efficacy at their respective alpha adrenoceptor subtypes. The results indicate that a receptor reserve exists for the alpha-1 and alpha-2 adrenoceptor-mediated effects of cirazoline and B-HT 933, respectively, and that the alpha adrenoceptor reserve may be significantly larger for postsynaptic vascular alpha-1 adrenoceptors than for postsynaptic vascular alpha-2 adrenoceptors in canine saphenous vein.(ABSTRACT TRUNCATED AT 250 WORDS)


[Smith-Magenis syndrome].
The main features of the Smith-Magenis syndrome include broad flat midface, brachycephaly, broad nasal bridge, brachydactyly, hoarse deep voice, speech and developmental delay, and behavioral anomalies. This syndrome is due to interstitial deletion of chromosome 17p11.2. A 7-year-old girl was admitted for mental retardation. Clinical examination showed brachycephaly, broad flat midface, broad nasal bridge, malar hypoplasia, brachydactyly, decreased or absent deep tendon reflexes, and hoarse deep voice. She had a mild deafness, behavioral problems, and sleep disturbances. Chromosome analysis on lymphocytes identified a microdeletion of one chromosome subband 17p11.2. Molecular studies indicated loss of maternal allele. The Smith-Magenis syndrome is probably underdiagnosed because of its usually mild clinical features. High-resolution chromosome analysis is needed for diagnosis.


The medial approach to the hip revisited.
Several muscular intervals have been described to approach the hip through a medial incision. We studied in detail the original descriptions of these surgical planes and found that several of them are nearly identical. We attempt to clarify the anatomic intervals available to the surgeon in hope of eliminating ambiguity in future reporting.


[The correlation of gastric secretory function and morphological changes in the gastric mucosa in peptic ulcer complicated by hemorrhage].
In 80% gastric ulcer and 86% duodenal ulcer observations Helicobacter pylori (HP) were revealed while observation of 124 patients with gastroduodenal ulcer disease, complicated by hemorrhage. Low pH of gastric contents was observed in the III-IV stages of blood loss. Stable rise of all indexes of gastric secretion was noted while III-IV stages of HP dissemination on the background of pronounced gastritis with dystrophic and inflammatory changes of its mucosa. The conformity between morphological changes of gastroduodenal mucosa, the blood loss intensity and the HP dissemination stage was noted.


Prevalence of stroke in an Argentine community.
To determine the prevalence of stroke and its distribution by age, sex and clinical type, and to use the outcomes for prevention, care and rehabilitation. The survey was conducted in Junín, a town of about 75,000 inhabitants, situated in an agricultural region of the Province of Buenos Aires, Argentina. Systematic sampling was used to select 5,839 dwellings (sampling fraction approximately 25%) and 5,648 (97%) households participated in our study, including 17,049 participants. The initial stage of the study involved a case-finding strategy consisting of a two-stage screening approach in the selected households; household screening was followed by neurological examination. We used a point prevalence with reference date January 1, 1991. Stroke was defined according to the WHO criteria. As of January 1, 1991, 148 subjects were identified as cases of stroke (79.6% ischemic and 20.4% hemorrhagic). Point prevalence ratio was 868.1 cases per 100,000 inhabitants in the total population (473.4/100,000 age adjusted to the worldwide population) and 1,867.4 in those patients of 40 years of age or older (1,534.4/100,000 age adjusted to the worldwide population). In both sexes, prevalence increased with age. However, this increase was more significant and sustained in men of 50 years of age and older. Moderate to severe disability was observed in 52% of patients. This is one of the first community-based studies conducted in Argentina about the prevalence of stroke. Final results are similar to those reported in other developed countries.


Identification of a stool long non-coding RNAs panel as a potential biomarker for early detection of colorectal cancer.
The feces of colorectal cancer (CRC) patients contain tumor colonocytes, which constantly shed into the lumen area. Therefore, stool evaluation can be considered as a rapid and low-risk way to directly determine the colon and rectum status. As long non-coding RNAs (lncRNAs) alterations are important in cancer cells fate regulation, we aimed to assess the level of a panel of cancer-related lncRNAs in fecal colonocytes. The population study consisted of 150 subjects, including a training set, a validation set, and a group of 30 colon polyps. The expression levels of lncRNAs were evaluated by quantitative real-time PCR (qRT-PCR). The NPInetr and EnrichR tools were used to identify the interactions and functions of lncRNAs. A total of 10 significantly dysregulated lncRNAs, including CCAT1, CCAT2, H19, HOTAIR, HULC, MALAT1, PCAT1, MEG3, PTENP1, and TUSC7, were chosen for designing a predictive panel. The diagnostic performance of the panel in distinguishing CRCs from the healthy group was AUC: 0.8554 in the training set and 0.8465 in the validation set. The AUC for early CRCs (I-II TNM stages) was 0.8554 in the training set and 0.8465 in the validation set, and for advanced CRCs (III-IV TNM stages) were 0.9281 in the training set and 0.9236 in the validation set. The corresponding AUC for CRCs vs polyps were 0.9228 (I-IV TNM stages), 0.9042 (I-II TNM stages), and 0.9362 (III-IV TNM stages). These data represented the application of analysis of fecal colonocytes lncRNAs in early detection of CRC.


Athlete medicine applied in a pandemic: disparities among athletes and performers reveal the need for a true 'revolution' in health care.
While society watches athletes and artists on a screen during the COVID-19 pandemic, some proponents tout 'normalcy' as the moment live in-action play resumes again. However, when we 'see' these athletes, are we truly seeing them? Failing to understand and address athletes' adversity faced during this pandemic amidst social pressures to return to play under a preconceived notion of 'normal' commoditises athletes; instead, we must humanise them while recognising additional burdens they bear amidst unmet healthcare needs. Athletes and performers represent a unique population; they stand at the intersection of racial and socioeconomic health inequity and societal expectations for entertainment. Returning to the field or stage suddenly, unscathed by effects of global viral and racial pandemics, is impossible. Instead, athletes face resuming play with a sobering realisation the pursuit of health is not fulfilled with the same tenacity for everyone. This editorial is to raise awareness to disparities that exist for athletes and performing artist athletes during the COVID-19 pandemic and beyond.


Alteration of REDD1-mediated mammalian target of rapamycin pathway and hypoxia-inducible factor-1α regulation in human breast cancer.
The purpose of this study is to investigate REDD1-(regulated in development and DNA damage response 1) mediated regulation of the mammalian target of rapamycin (mTOR) pathway in breast cancer. A tissue microarray included samples from 224 patients with breast cancer, and 30 patients with papilloma were used as a control group. An immunohistochemistry (IHC) including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), epithelial growth factor receptor, cytokeratin 5/6, glucose transporter 1 (Glut-1), hypoxia-inducible factor (HIF)-1α, REDD1, AMPK (5'-adenosine-monophosphate-activated protein kinase) α(1), 14-3-3σ, phosphatase and tensin homolog, phospho-Akt, phospho-mTOR, phospho-S6, and Ki-67 was conducted. The phenotypic classification of breast cancer was performed based on the results of the IHC for ER, PR and HER2: luminal A, luminal B, HER2 overexpression and triple-negative breast cancer (TNBC). Glut-1 and HIF-1α were more highly expressed in TNBC, the HER2 overexpression type and papilloma than in the luminal A and B phenotypes (p = 0.000). REDD1 expression was higher in papilloma than in breast cancer (p = 0.000), but no difference was found among the 4 breast cancer phenotypes (p = 0.307). In the HER2 overexpression type and TNBC, tumor cell proliferation and survival in the hypoxic tumor environment could possibly be due to disinhibition of the mTOR pathway and HIF-1α stabilization by downregulation of REDD1.


Modeling and simulation of nanoparticle separation through a solid-state nanopore.
Recent experimental studies show that electrokinetic phenomena such as electroosmosis and electrophoresis can be used to separate nanoparticles on the basis of their size and charge using nanopore-based devices. However, the efficient separation through a nanopore depends on a number of factors such as externally applied voltage, size and charge density of particle, size and charge density of membrane pore, and the concentration of bulk electrolyte. To design an efficient nanopore-based separation platform, a continuum-based mathematical model is used for fluid. The model is based on Poisson-Nernst-Planck equations along with Navier-Stokes equations for fluid flow and on the Langevin equation for particle translocation. Our numerical study reveals that membrane pore surface charge density is a vital parameter in the separation through a nanopore. In this study, we have simulated high-density lipoprotein (HDL) and low-density lipoprotein (LDL) as the sample nanoparticles to demonstrate the capability of such a platform. Numerical results suggest that efficient separation of HDL from LDL in a 0.2 M KCL solution (resembling blood buffer) through a 150 nm pore is possible if the pore surface charge density is ∼ -4.0 mC/m(2). Moreover, we observe that pore length and diameter are relatively less important in the nanoparticle separation process considered here.


Reliability and validity of nasality ratings between a monolingual and bilingual listener for speech samples from English-Spanish-Speaking children.
This study sought to determine if a monolingual English listener could rate nasality in English and in Spanish with the same proficiency as a bilingual English-Spanish listener, and to compare nasalance scores with nasality ratings. Speakers for this study were 26 bilingual English-Spanish-speaking children. Speech samples and nasalance scores were obtained simultaneously as each speaker recited one English sentence and one Spanish sentence. A monolingual listener and a bilingual listener rated nasality. For the English sentences, the intrajudge correlation coefficient was r = 0.89 for the monolingual listener and r = 0.89 for the bilingual listener. For the Spanish sentences, the intrajudge correlation coefficient was r = 0.91 for the monolingual listener and r = 0.92 for the bilingual listener. Interjudge agreement was r = 0.86 for rating English sentences and r = 0.78 for rating Spanish sentences. All correlation coefficients were significant (p < 0.001). The correlation coefficients between nasality ratings and nasalance scores were essentially the same for both listeners and both languages. A monolingual and a bilingual judge had high agreement on ratings of nasality for English and Spanish speech. The relationship between nasalance and nasality was not different across languages.


[Analysis of proteins in the extracts of Physalis alkekengi L. var. franchetii (Mast.) Makino using nanoflow reversed-phase liquid chromatography-tandem mass spectrometry].
The protein was extracted from Physalis alkekengi L. var. franchetii (Mast.) Makino fruit by using water extraction and acid precipitation methods, and it consisted of 188 mg/g of protein on dry basis of the extract. Among 18 amino acids, eight essential amino acids for human account for 31% were found in this extract. Based on shotgun proteomics method, the protein extracted from Physalis fruit was analysed by nanoflow reversed-phase liquid chromatography-tandem mass spectrometry (nano-RPLC-MS/MS) system. Combined with database searches and bioinformatics analysis, the protein species and six molecular functions were identified, including with catalytic activity, antioxidant activity, enzyme regular activity, nutrient reservoir activity, transporter activity and binding activity. And three antioxidant activity-related proteins were identified. These results may lay the foundation for further study of the functional properties of the proteins in Physalis fruit.


Superior cervical sympathetic ganglion block under ultrasound guidance promotes recovery of abducens nerve palsy caused by microvascular ischemia.
The abducens nerve palsy is most likely caused by microvascular issue. Spontaneous recovery of vasculopathic abducens nerve palsies was common at 3-6 months. But recovery time was longer when many risk factors were present. Several patients had residual esotropia or abduction deficit. Cervical sympathetic block has an established use in treating patients with disorders related to cranial circulatory insufficiency. It causes a significant increase in cerebral blood flow. We report a case of a 67-year-old man with acute horizontal diplopia and right periocular pain. He had been diagnosed with right abducens nerve palsy caused by microvascular ischemia. We performed ultrasound-guided superior cervical sympathetic ganglion blocks. After 4 weeks, the symptoms had been completely resolved. We introduce ultrasound-guided superior cervical sympathetic ganglion blocks for management of abducens nerve palsy caused by microvascular ischemia, which could be an effective novel method to promote recovery from diplopia.


Overexpression of DEC1 in the epithelium of OSF promotes mesenchymal transition via activating FAK/Akt signal axis.
Previous studies on oral submucous fibrosis (OSF) mostly focused on the activation of fibroblasts and collagen metabolism, while little involved in the epithelium. As we have reported the role of differentiated embryo-chondrocyte expressed gene 1 (DEC1) in oral cancer and other precancerous lesions, this research aimed to explore its role in the OSF epithelium. Expression of DEC1 and other proteins were investigated in tissue array constructed with 33 OSF and 14 normal oral mucosa (NOM) tissues. Human oral keratinocytes treated with arecoline and/or hypoxia were used to simulate OSF epithelium and detected for morphological and protein alterations. Inhibition of DEC1 was used to explore its mediating role. Finally, animal models of OSF constructed by locally arecoline injecting in buccal mucosa were used to verify our findings. DEC1 overexpression could be detected in the epithelium of OSF compared with that in NOM followed by phosphorylated FAK and Akt, and DEC1 showed a significant positive correlation with them. Cytology experiment revealed that OSF-like treatment could upregulate DEC1 expression followed by phosphorylated FAK, Akt, but inhibit E-cadherin, while knockdown of DEC1 could suppress the effects. In addition, OSF mice revealed higher expression of DEC1 in the epithelium of buccal mucosa, along with synchronized alterations of phosphorylated FAK and Akt. In the epithelium of OSF, overexpression of DEC1 induced activation of FAK/Akt signal axis, caused mesenchymal transition in epithelial cells, and may promote malignant transformation of OSF. Targeting DEC1 in OSF could be promising a new target for the diagnosis and treatment of this process.


[Clinical information system and its significance in intensive care].
The increasing number of the patients requiring admission to the intensive care unit and growing demand for the outcome analysis was noted over the last decade. The goal of this study was to evaluate the characteristics of the patients, to compare the outcome of surgical and medical patients, and to demonstrate the importance of the clinical information system in the intensive care. During 12-month period 1031 patients were enrolled for the study. Data were collected on forms and then entered into a computer program specifically designed for this study. For the overall population mean age was 63 years, Simplified Acute Physiology Score II (SAPS II)--31, and stay in the intensive care unit--4 days. The most frequent site of the intensive care unit acquired infection was respiratory, mainly pneumonia. The overall mortality in the intensive care unit was 19.4% and hospital mortality--24.8%. The mortality was directly associated with advanced age, increased SAPS II sore, and the occurrence of organ dysfunction. Medical patients in comparison with surgical patients had higher SAPS II scores (p < 0.001) and number of organ dysfunctions (p < 0.001), longer intensive care unit stay (p < 0.001) and higher mortality rate (p < 0.001). The underprediction of actual mortality by the SAPS II system was predetermined by this value of the neurological patients. The outcome of the surgical patients was good compared to the results of the studies from other countries. Clinical information system is necessary for comprehensive and objective evaluation of the intensive care unit data and quality of therapy.


The septic syndrome. An oncologic treatment challenge.
The septic syndrome has three phases, characterized by alterations in tissue perfusion (phase I), fluid volume (phase II), and cardiac output (phase III). It must be viewed as a continuum: the degree of illness and the rate of mortality increase with each stage. Each phase must be clearly understood by health-care professionals for them to be able to intervene actively to prevent a patient's progressive deterioration. Since the septic syndrome frequently cannot be treated effectively in the advanced stage, the nurse's role must focus on early detection of infection, thorough evaluation of all the parameters, and expeditious initiation of treatment in collaboration with the physician. The high mortality of cancer patients who develop septic shock is an incentive for nurse and physician to work together to prevent this serious condition and provide maximum support if it should occur. The nurse's ability to make critical judgments derived from a knowledgeable assessment of clinical data can positively influence the outcome. The timeliness of the nursing intervention may determine the patient's fate.


On the possible central effects of calcium antagonists.
The present paper discusses the possible central effects of calcium antagonists on the central nervous system in the light of present knowledge of the role of Ca2+ in physiological and pathophysiological processes.


Instrumented Four Square Step Test in Adults with Transfemoral Amputation: Test-Retest Reliability and Discriminant Validity between Two Types of Microprocessor Knees.
Technology-based outcomes have recently been proposed to complement the standard Four Square Step Test (FSST) by providing a decomposition of the sequences and information about the stepping pattern. A test-retest study and a randomized crossover design have been used to determine immediate test-retest reliability and to assess discriminant validity, in persons with a unilateral transfemoral amputation, for the parameters computed by an instrumented version of the Four Square Step Test. Twenty adults, independent and unlimited community ambulators, with a unilateral transfemoral amputation, performed two Four Square Step Tests on a pressure mat first with a microprocessor knee, then, a few weeks later with another one. One of these prosthetic knees was acknowledged to be superior and to provide functional improvement. Test-retest, intraclass correlation coefficients and minimal detectable change at 95% confidence level were calculated for each variable. Paired samples t-tests were then used to identify differences between the two microprocessor knee systems. The test-retest reliability of most outcome measures was good to excellent. Few variables showed a systematic difference and a trend to improve between test 1 and test 2. When comparing both microprocessor knees, significant differences in the expected direction were observed, with interpretation in accordance with a functional improvement. Importantly, we highlighted that various strategies to improve the performance in the test might complexify the interpretation of the most detailed measurement. The instrumented Four Square Step test provides reliable measures with satisfactory test-retest reliability and discriminant validity in persons with unilateral transfemoral amputation.


Strategy for applying genome-wide selection in dairy cattle.
Animals can be genotyped for thousands of single nucleotide polymorphisms (SNPs) at one time, where the SNPs are located at roughly 1-cM intervals throughout the genome. For each contiguous pair of SNPs there are four possible haplotypes that could be inherited from the sire. The effects of each interval on a trait can be estimated for all intervals simultaneously in a model where interval effects are random factors. Given the estimated effects of each haplotype for every interval in the genome, and given an animal's genotype, a 'genomic' estimated breeding value is obtained by summing the estimated effects for that genotype. The accuracy of that estimator of breeding values is around 80%. Because the genomic estimated breeding values can be calculated at birth, and because it has a high accuracy, a strategy that utilizes these advantages was compared with a traditional progeny testing strategy under a typical Canadian-like dairy cattle situation. Costs of proving bulls were reduced by 92% and genetic change was increased by a factor of 2. Genome-wide selection may become a popular tool for genetic improvement in livestock.


Budgerigar breeders' hypersensitivity pneumonitis presenting as chronic bronchitis with purulent sputum.
A 49-year-old woman complained of cough and a purulent sputum (about 40 ml/day). She kept budgerigars for a period of 30 years, she first noticed a productive cough 10 years previously. Her chest roentgenogram revealed a diffuse reticulonodular pattern. She was diagnosed as having a chronic type of budgerigar breeder's lung associated with chronic bronchitis. Peptostreptococcus anaerobius was cultured from her sputum, bronchoalveolar lavage fluid, as well as from droppings of her budgerigar. This is the second case of hypersensitivity pneumonitis presenting as chronic bronchitis with much sputum in Japan.


Encapsulation of Sulfur into N-Doped Porous Carbon Cages by a Facile, Template-Free Method for Stable Lithium-Sulfur Cathode.
Lithium-sulfur (Li-S) batteries with a high energy density and long lifespan are considered as promising candidates for next-generation electrochemical energy-storage devices. However, the sluggish redox kinetics of electrochemistry and high solubility of polysulfide during cycling render insufficient sulfur utilization and poor cycling stability. Herein, a facile, template-free procedure based on controlled pyrolysis of polydopamine vesicles is described to prepare N-doped porous carbon cages (NHSC) as a new sulfur host, which significantly improves both the sulfur utilization and cycling stability. As NHSC shows a high pore volume, continuous electron and ion transport paths, and good catalytic activity, encapsulation of S nanoparticles into NHSC endows the resulting S@NHSC electrode with a good energy storage capacity and exceptionally high electrochemical stability. Consequently, a Li-S cell with the S@NHSC as the cathode achieves a high initial capacity of 1280.7 mAh g-1 , and cycling stability over 500 cycles with the capacity decay as low as 0.0373% per cycle.


Response normalized liquid chromatography nanospray ionization mass spectrometry.
The widely different LC-MS response observed for many structurally different compounds limits the use of LC-MS in full scan detection mode for quantitative determination of drugs and metabolites without using reference standard. The recently introduced nanospray ionization (NSI) technique shows comparable MS response for some compounds under non-LC-MS conditions. However, in the presence of numerous endogenous compounds commonly associated with biological samples such as urine, plasma, and bile, LC-MS is required to separate, detect, identify, and measure individual analytes. An LC-NSI-MS system was devised and the MS response obtained in this system for a variety of pharmaceutical drugs and their metabolites. The set-up involves two high-performance liquid chromatography (HPLC) systems, a chip-based NSI source and a quadrupole-time-of-flight (Q-TOF) mass spectrometer. Herein this is referred to as the response normalized-liquid chromatography NSI-MS (RNLC-NSI-MS) system. One HPLC unit performs the analytical separation, while the other unit adds solvent post-column with an exact reverse of the mobile phase composition such that the final composition entering the NSI source is isocratic throughout the entire HPLC run. The data obtained from four different structural classes of compounds [vicriviroc (VCV), desloratadine (DL), tolbutamide, and cocaine] and their metabolites indicate that by maintaining the solvent composition unchanged across the HPLC run, the influence of the solvent environment on the ionization efficiency is minimized. In comparison to responses obtained from radiochromatograms, responses from conventional LC-ESI-MS overestimated the VCV and DL responses, respectively, by 6- and 20-fold. Although VCV and DL responses obtained using LC-NSI-MS are within 2- to 6-fold from the respective radiochromatographic responses, the response normalization modification results in nearly uniform LC-NSI-MS response for all compounds evaluated.


[Massive pulmonary embolism similar to acute myocardial infarction rescued by ECMO: a case report].
Acute myocardial infarction (AMI) and acute massive pulmonary embolism can be characterized by no pulse electrical activity. Patients of cardiac arrest (CA) with no pulse electrical activity have a high mortality rate before the cause was corrected. Extracorporeal membrane oxygenation (ECMO), as a kind of artificial heart-lung support organ, provides treatment for CA patients. A case of massive pulmonary embolism similar to AMI was treated in the Third Central Hospital of Tianjin, who received interventional thrombolysis assisted by ECMO. Through the review of the overall development of the case, we aim to broaden the diagnosis and treatment of CA patients with no pulse electrical activity, and to improve the understanding of the complications secondary to ECMO.


Formation of triploid plants via possible polyspermy.
Polyploidization is a common phenomenon in angiosperms, and polyploidy has played a major role in the long-term diversification and evolutionary success of plants. Triploid plants are considered as the intermediate stage in the formation of stable autotetraploid plants, and this pathway of tetraploid formation is known as the triploid bridge. As for the mechanism of triploid formation among diploid populations, fusion of an unreduced gamete with a reduced gamete is generally accepted. In addition, the possibility of polyspermy has been proposed for maize, wheat and some orchids, although it has been regarded as an uncommon mechanism of polyploid formation. One of the reasons why polyspermy is regarded as uncommon is because it is difficult to reproduce the polyspermy situation in zygotes and to analyze the developmental profiles of polyspermic zygotes. In the study, we produced polyspermic rice zygotes by electric fusion of an egg cell with two sperm cells and monitored their developmental profiles. The two sperm nuclei and the egg nucleus fused into a zygotic nucleus in the polyspermic zygote, and the triploid zygote divided into a two-celled embryo via mitotic division with a typical bipolar microtubule spindle. The two-celled proembryos developed and regenerated into triploid plants. These results suggest that polyspermic plant zygotes have the potential to form triploid embryos, and that polyspermy in angiosperms might be a pathway for the formation of triploid plants.


Case Report: Challenges for the Diagnosis and Treatment of Strongyloides stercoralis in Chronic Obstructive Pulmonary Disease Patients.
Strongyloidiasis, a neglected tropical disease (NTD), which is caused by Strongyloides stercoralis, can be fatal in immunocompromised patients. In most chronic cases, infections most frequently are asymptomatic, and eosinophilia might be the only clinical characteristic of this disease. The use of corticosteroids in some diseases like chronic obstructive pulmonary disease (COPD) may lead to the development of the life-threatening S. stercoralis hyperinfection syndrome. In the present research, we presented five cases of strongyloidiasis with a history of COPD and receiving corticosteroids from Abadan County, southwestern Iran. By performing the direct smear stool examinations, two cases were identified and the other three cases were diagnosed using the agar plate culture method. Despite reporting eosinophilia in previous patients' hospitalizations, the fecal examination was not performed for parasitic infections. Moreover, pulmonary symptoms were similar, but gastrointestinal symptoms were varied, including nausea, vomiting, abdominal pain, epigastric pain, constipation, and diarrhea. All the included patients were treated with albendazole, which is the second-line drug for S. stercoralis, and relapse of infection was observed in two patients by passing few months from the treatment. The increased blood eosinophil count was shown to play important roles in both the management of COPD and diagnosis of helminthic infections. In COPD patients who are receiving steroids, screening and follow-up for strongyloidiasis should be considered as priorities. In addition, ivermectin, which is the first-line drug for strongyloidiasis, should be available in the region.


Screening patients for risk of sleep apnea using facial photographs.
We investigated using frontal and profile facial photographic images for screening patients for risk of sleep apnea. A 180 image pairs were used from patients who were diagnosed using an attended overnight polysomnogram test into controls (AHI<;10/h) and sleep apnea (AHI≥10/h). A series of 35 landmarks and 71 features motivated by craniofacial structure pertinent to upper airway physiology were identified on the photographs. After reducing the dimension of the feature set using recursive feature selection, the features were processed by a Support Vector Machine (SVM). Classification was performed using linear kernel SVM. The accuracy and area under Receiver Operating Curve (ROC) improved when the number of features reduced from 71 to eight top-ranked features. Further improvement was achieved by adding clinical measurements to the selected features resulting in the accuracy of 80% and the area under ROC of 0.83.


Effects of Naphthazarin (DHNQ) Combined with Lawsone (NQ-2-OH) or 1,4-Naphthoquinone (NQ) on the Auxin-Induced Growth of Zea mays L. Coleoptile Segments.
Naphthoquinones, plants secondary metabolites are known for their antibacterial, antifungal, anti-inflammatory, anti-cancer and anti-parasitic properties. The biological activity of naphthoquinones is connected with their ability to generate reactive oxygen species and to modify biological molecules at their nucleophilic sites. In our research, the effect of naphthazarin (DHNQ) combined with 2-hydroxy-1,4-naphthoquinone (NQ-2-OH) or 1,4-naphthoquinone (1,4-NQ) on the elongation growth, pH changes of the incubation medium, oxidative stress and redox activity of maize coleoptile cells were investigated. This paper describes experiments performed with maize (Zea mays L.) coleoptile segments, which is a classical model system to study plant cell elongation growth. The data presented clearly demonstrate that lawsone and 1,4-naphthoquinone combined with naphthazarin, at low concentrations (1 and 10 nM), reduced the endogenous and IAA-induced (Indole-3-Acetic Acid) elongation growth of maize coleoptile segments. Those changes in growth correlated with the proton concentration in the incubation medium, which suggests that the changes in the growth of maize coleoptile segments observed in the presence of naphthoquinones are mediated through the activity of PM H⁺-ATPase. The presence of naphthoquinones induced oxidative stress in the maize coleoptile tissue by producing hydrogen peroxide and causing changes in the redox activity. Moreover, the incubation of maize segments with both naphthoquinones combined with naphthazarin resulted in lipid peroxidation and membrane damage. The regulation of PM H⁺-ATPase activity, especially its inhibition, may result from two major types of reaction: first, a direct interaction between an enzyme and naphthoquinone, which leads to the covalent modification of the protein thiols and the generation of thioethers, which have been found to alter the activity of the PM H⁺-ATPases; second, naphthoquinones induce reactive oxygen species (ROS) production, which inhibits PM H⁺-ATPases by increasing cytosolic Ca2+. This harmful effect was stronger when naphthazarin and 1,4-naphthoquinone were added together. Taking these results into account, it can be suggested that by combining naphthoquinones in small quantities, an alternative to synthetic pesticides could be developed.


Use of dextran-40 gradients for separation of pea cotyledon mitochondria into different fractions.
A crude pea (Pisum sativum L. var. Homesteader) mitochrondrial preparation was divided into two equal parts. One part was layered on a Dextran-40 step gradient, and the other on a sucrose step gradient, and they were centrifuged to obtain different bands of particles. The densities at which the particles banded and the mitochondrial respiratory activities of the particles were determined. Dextran-40 density gradient centrifugation resulted in a better separation of mitochondrial populations than did sucrose density gradient centrifugation. Separation by sucrose density gradient centrifugation may not be according to the true densities of the particles. On the other hand, the use of gradients of Dextran-40, a solute of low osmotic potential, facilitated separation of particles acording to their true densities. Such mitochondria showed better respiratory control ratio and ADP:0 values, than those isolated by sucrose density gradient centrifugation.


Variation in the incidence of AGUS between different patient populations.
To determine the frequency of atypical glandular cells of undetermined significance (AGUS) for three consecutive calendar years from three different referral sources. Cervicovaginal smears with a diagnosis of AGUS were identified from January 1995 through December 1997. The smears were submitted from three different sources: two were city government hospital clinics, one with predominantly African American and Hispanic patients and the other with predominantly Asian and Hispanic patients. The third referral source was private practitioners' offices with predominantly Caucasian patients. A diagnosis of AGUS was made in 707 cases, accounting for 0.56% of all smears examined. This was in contrast to 6,872 smears reported as atypical squamous cells of undetermined significance (ASCUS) (5.4%) and 3,347 reported as squamous intraepithelial lesions (SIL) or above (2.7%). The incidence of AGUS ranged from 0.16% to 1.00% among different patient populations. This difference was also noted in the rate of ASCUS and SIL in the same patient population. There was a steady increase in the rate of AGUS for each referral source during the study period. The overall rate of patients who underwent histologic evaluation and the incidence of biopsy-proven preinvasive and invasive lesions were 62.4% and 23%, respectively. There was no significant difference in the rate of significant lesions after a diagnosis of AGUS during the study period or between the three referral sources. The AGUS rate in our laboratory was low and within the range (0.17-1.83%) reported in the literature. The AGUS rate varies with different patient populations, particularly with the incidence of SIL and age distribution.


Analyses of joint variance related to voluntary whole-body movements performed in standing.
This article investigates two methodological issues resulting from a recent study of center of mass positional stability during performance of whole-body targeting tasks (Freitas et al., 2006): (1) Can identical results be obtained with uncontrolled manifold (UCM) variance analysis when it is based on estimating the Jacobian using multiple linear regression (MLR) analysis compared to that using typical analytic formal geometric model? (2) Are kinematic synergies more related to stabilization of the instantaneous anterior-posterior position of the center of mass (COM(AP)) or the center of pressure (COP(AP))? UCM analysis was used to partition the variance of the joint configuration into 'bad' variance, leading to COM(AP) or COP(AP) variability, and 'good' variance, reflecting the use of motor abundance. Findings indicated (1) nearly identical UCM results for both methods of Jacobian estimation; and (2) more 'good' and less 'bad' joint variance related to stability of COP(AP) than to COM(AP) position. The first result requires further investigation with more degrees of freedom, but suggests that when a formal geometric model is unavailable or overly complex, UCM analysis may be possible by estimating the Jacobian using MLR. Correct interpretation of the second result requires analysis of the singular values of the Jacobian for different performance variables, which indicates how certain amount of joint variance affects each performance variable. Thus, caution is required when interpreting differences in joint variance structure among various performance variables obtained by UCM analysis without first investigating how the different relationships captured by the Jacobian translate those variances into performance-level variance.


Biases in ecological studies: utility of including within-area distribution of confounders.
This paper is centred on studies commonly known as ecological studies, where one seeks to estimate risks from data aggregated on a geographical basis. The aggregated nature of the data creates difficulties for interpreting, at an individual level, any ecological association found, difficulties which are generically referred to as 'the ecological bias or fallacy'. Here, we address an important component of this bias related to the problem of misspecification in ecological studies. We consider how aggregated level dose-response relationships are derived from integrating individual level ones over the group, and how their correct specification requires, in general, knowledge of the within-group joint distribution of the relevant risk factors, which is rarely available. We discuss in detail the common situation where data on the proportion of persons exposed in each area to several dichotomous risk factors are available. We show that ecological regression estimates of the relative risk for each factor will be improved by including in the regression, besides the linear terms, cross-product terms of the marginal prevalences. Results from a simulation study are discussed and an example concerning the geographical analysis of lung cancer mortality in France is presented.


[Role of thymocytes in the correlation between the thymus and hypophysis].
The influence of the thymus on the growth hormone (GH) level in the mouse hypophysis has been studied. It has been found, that syngeneic transfer of thymocytes of young mice into thymectomized mice causes on increase of the growth hormone level in the hypophysis. Administration of hydrocortisone simultaneously with transfer of thymocytes accelerated the GH level increase. The administration of only hydrocortisone into thymectomized mice does not lead to changes in the GH level. The increased GH level was observed when thymocytes were replaced by some structures shedding from thymocytes after their stimulation with short peptide thymic hormone. It is supposed that thymocytes can stimulate GH accumulation in the hypophysis.


Improvement of the Ocular Bioavailability of Econazole Nitrate upon Complexation with Cyclodextrins.
Econazole nitrate (EC) is an active, imidazole antifungal agent. However, low aqueous solubility and dissolution rate of EC has discouraged its usage for the treatment of ophthalmic fungal infection. In this study, inclusion complexes of EC with cyclodextrins were prepared to enhance its solubility, dissolution, and ocular bioavailability. To achieve this goal, EC was complexed with β-CyD/HP-β-CyD using kneading, co-precipitation, and freeze-drying techniques. Phase-solubility studies were performed to investigate the complexes in the liquid form. Additionally, the complexes in the solid form were characterized with Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and transmission electron microscopy (TEM). Furthermore, different eye drops containing EC-CyD complexes were prepared using different polymers and then characterized regarding their drug contents, pH, viscosity, mucoadhesive strength, and in vitro release characteristics. The results showed that stable EC-CyD complexes were formed in 1:1 molar ratio as designated by BS-type diagram. Econazole nitrate water solubility was significantly increased in about three- and fourfold for β-CyD and HP-β-CyD, respectively. The results showed that the prepared complexes were spherical in shape having an average particle diameter from 110 to 288.33 nm with entrapment efficiency ranging from 64.24 to 95.27%. DSC investigations showed the formation of real inclusion complexes obtained with co-precipitation technique. From the in vitro studies, all eye drops containing co-precipitate complexes exhibited higher release rate than that of other complexes and followed the diffusion-controlled mechanism. In vivo study proved that eye drops containing EC-CyD complexes showed higher ocular bioavailability than EC alone which indicated by higher AUC, Cmax, and relative bioavailability values.


Physical exercise as a tool to minimize the consequences of the Covid-19 quarantine: An overview for cystic fibrosis.
Coronavirus (SARS-CoV-2) outbreak leading to the coronavirus disease (Covid-19) has become a global pandemic. Patients with Cystic fibrosis are considered of major risk, as respiratory tract infections are more severe than in the general population, with a higher risk of complications and a negative impact on lung function. The performance of physical exercise is considered as key for its well-known general benefits and also as a complementary method to help airway clearance. Therefore, physical exercise is also considered as key in the therapeutic strategy during the quarantine period. However, the impossibility to perform exercise with appropriate prescription and monitoring is of considerable worry to health care professionals. Thus, alternative strategies, such as online measures to monitor this therapy and, consequently, to achieve a safe and effective dose are highly needed. Exercise regimens should include strength and endurance, as well as balance and flexibility exercises. Patients are highly encouraged to participate in exercise programs to maintain fitness and exercise should be continued during the quarantine period. This commentary provides a summary of the main effects and benefits of physical exercise, as well as the main recommendations for its adequate execution, including exercise modality, frequency, intensity, and volume.


Radiocapitellar Impingement after a Pediatric Type II Capitellar Fracture.
We present a case of radiocapitellar impingement caused by osteochondral fragment after type II capitellar fracture. Painful extension limitation of the elbow was treated successfully by diagnostic arthroscopy and mini-open removal of loose body. A displaced type II capitellar fracture in children is extremely rare, but must be carefully diagnosed and treated.


Quantitative analysis of the novel depsipeptide anticancer drug Kahalalide F in human plasma by high-performance liquid chromatography under basic conditions coupled to electrospray ionization tandem mass spectrometry.
Kahalalide F (KF) is a novel cyclic depsipeptide anticancer drug, which has shown anticancer activity both in vitro and in vivo especially against human prostate cancer cell lines. To characterize the pharmacokinetics of KF during a phase I clinical trial in patients with androgen refractory prostate cancer, a method was developed and validated for the quantitative analysis of KF in human plasma using high-performance liquid chromatography (HPLC) coupled to positive electrospray ionization tandem mass spectrometry (ESI-MS/MS). Microbore reversed-phase liquid chromatography (LC) performed with mobile phases containing trifluoroacetic acid, an additive commonly used for separating peptides, resulted in substantial suppression of the signal for KF on ESI-MS/MS. An alternative approach employing a basic mobile phase provided an excellent response for KF when detected in the positive ion mode. Plasma samples were prepared for LC MS/MS by solid-phase extraction on C(18) cartridges. The LC separation was performed on a Zorbax Extend C(18) column (150 x 2.1 mm i.d., particle size 5 micro m) with acetonitrile -10 mM aqueous ammonia (85 : 15, v/v) as the mobile phase, at a flow-rate of 0.20 ml min(-1). A butyric acid analogue of KF was used as the internal standard. The lower limit of quantitation (LLQ) using a 500 micro l sample volume was 1 ng ml(-1) and the linear dynamic range extended to 1000 ng ml(-1). The inter-assay accuracy of the assay was -15.1% at the LLQ and between -2.68 and -9.05% for quality control solutions ranging in concentration from 2.24 to 715 ng ml(-1). The inter-assay precision was 9.91% or better at these concentrations. The analyte was stable in plasma under all relevant conditions evaluated and for a period of 16 h after reconstituting plasma extracts for LC analysis at ambient temperature.


Fracture of the polyethylene component in an ankle arthroplasty: a case report.
A 57-year-old female underwent total ankle arthroplasty for post-traumatic arthrosis using the Agility Total Ankle System. The talar component was placed in varus malalignment. Her postoperative course was remarkable for 19 months of satisfactory function followed by the acute onset of intense pain and decreased range of motion. There was no history of trauma. After failing a short course of observation, revision surgery of the arthroplasty was performed. Operative findings revealed a complete fracture of the polyethylene. This report details the first case of such a complication and discusses the importance of component alignment in the prevention of polyethylene insert failure.


Split lateral iliac crest chimera flap: utility of the ascending branch of the lateral femoral circumflex vessels.
Complex head and neck reconstruction often requires multiple tissue components to restore form and function to the traumatized area. Here, the authors describe the split lateral iliac crest chimera flap and demonstrate the utility of the ascending branch of the lateral femoral circumflex system to provide vascularized bone for complex head and neck reconstruction. A retrospective case series analysis was performed for patients undergoing complex head and neck reconstruction utilizing the split lateral iliac crest chimera flap to provide vascularized bone and soft tissue. The blood supply to the lateral iliac crest was via the ascending branch of the lateral femoral circumflex system, and the soft tissue was supplied by the transverse and descending branches of the circumflex system. Four patients with advanced recurrent head and neck cancer undergoing split lateral iliac crest chimera reconstruction between November of 2007 and April of 2009 were included. Three patients required reconstruction of segmental mandibulectomy defects, and one required reconstruction of a maxillectomy defect. All components of the chimeric flaps in each patient survived. Bone vascularity was confirmed with triphasic bone scans within the first week postoperatively in two patients. The split lateral iliac crest chimera flap employs distinct branches of the lateral femoral circumflex system to supply the split lateral iliac crest and soft tissue of the thigh, each isolated on separate vascular leashes connected to a common source vessel. Through inclusion of a vascularized bone component, the flap extends the versatility of the lateral femoral circumflex flap for complex head and neck reconstruction requiring both hard-tissue and soft-tissue replacement.


[A pathological and histochemical study of capsules of impacted teeth with special reference to keratin immunohistochemistry in the lining epithelium].
The purpose of this study was to examine and understand the nature of capsules consisted of fifty cases of unerupted wisdom teeth using radiological, pathological and immunohistochemical methods. Radiologically, the pericoronal space was measured with slide caliper and divided into three groups (-0.9 mm, 1.0-1.9 mm, 2.0mm). Pathologically, all specimens were examined by the routine paraffin method and were stained with hematoxylin.eosin and PAS-alcian blue pH 2.5 stainings. Immunohistochemically, PAP (peroxidase-antiperoxidase) method using various keratin antibodies, such as, anti-keratin K 528 (40-68 KD), anti-cytokeratin PKK 1 (40, 45, 52.5 KD), anti-cytokeratin PKK 2 (40, 46, 48, 54 KD), anti-keratin A 575 (56, 64 KD) and anti-cytokeratin high molecular weight (68 KD), and other various antibodies of anti-EMA, anti-IgA and anti-SC was used in order to study the nature of the epithelium of capsule of impacted teeth. The following results were obtained; 1. Radiologically, the width of the capsules was 1.6 mm in the average. Histopathologically, the inner surface of the capsule was covered with two types of epithelium which were composed of non-typical epithelium with cuboidal (basal layer) and columnar (superficial layer) cells, and typical stratified squamous epithelium. The epithelium lining was observed in 74% of all cases. Among the cases, cyst like structure was more often seen in the cases with typical squamous epithelial lining and with pericoronal space more than 1.0 mm width. 2. In the connective tissue's findings of capsules of impacted teeth, fibrosis was found in almost all the cases. Inflammatory and myxomatous changes were recognized in ca. half cases. Epithelial rest and calcification with dystrophy and epithelial product were observed in about one third of the cases. The epithelial proliferation in the capsule was also rarely seen in the specimens. 3. Immunohistochemically, keratins of 56 KD and 64 KD were identified in the superficial layer of non-typical epithelium and basal, intermediate and superficial layers of the typical squamous epithelium of the capsules of imparted teeth. Keratin of 68 KD was only observed in superficial layer of squamous epithelium. 4. Epithelial membrane antigen was positive in the intermediate and superficial layers of typical squamous cell epithelium. However, it was not seen in the non-typical epithelium of capsule of impacted teeth. 5. Immunoglobulin A and secretory component were negative in the epithelia of capsules.


Comprehensive genomic and phenotypic characterization of germline FH deletion in hereditary leiomyomatosis and renal cell carcinoma.
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a familial cancer syndrome associated with the development of cutaneous and uterine leiomyomas, and an aggressive form of type 2 papillary kidney cancer. HLRCC is characterized by germline mutation of the FH gene. This study evaluated the prevalence and clinical phenotype of FH deletions in HLRCC patients. Patients with phenotypic manifestations consistent with HLRCC who lacked detectable germline FH intragenic mutations were investigated for FH deletion. A series of 28 patients from 13 families were evaluated using a combination of a comparative genomic hybridization (CGH) array and/or CLIA-approved FH deletion/duplication analyses. Thirteen distinct germline deletions were identified in the 13 UOB families, including 11 complete FH gene deletions and 2 partial FH gene deletions. The size of eight evaluated complete FH deletions varied from ∼4.74 Mb to 249 kb, with all deletions resulting in additional gene losses. Two partial FH gene deletions were identified, with one resulting in loss of exon 1 and the upstream region of the FH gene only. Kidney cancer was diagnosed in 9 (32%) of 28 patients and 7 (54%) of 13 families possessing either complete or partial FH deletions. Cutaneous and uterine leiomyomas were observed at similar rates to those in FH point mutation families. Complete or partial FH gene alterations in HLRCC families are associated with all of the canonical HLRCC manifestations, including type 2 papillary kidney cancer and should be screened for in any patient at-risk for this disorder.


Immunostimulatory effect of coumarin derivatives before and after infection of mice with the parasite Schistosoma mansoni.
Coumarins (pyranobenzopyran derivatives) (coumarin: CAS 91-64-5), organic compounds of known chemotherapeutic importance against bacteria, infectious diseases and tumors, were tested for their immunomodulatory effects. The compounds used in the present study were 1H,9H-3-amino-7-methyl-9-oxo-1-phenylpyran(2,3-h)(1)benzopyran-2-carbonitrile; 1H,9H-2-carboxamido-7-methyl-3,9-dioxo-1-phenylpyran(2,3-h)(1)benzopyran; 4H,8H-2-amino-7-bromo-6-methyl-10-nitro-8-oxo-4-(p-nitrophenyl)-pyran(3,2-g)(1)benzopyran-3-carbonitrile; 4H-7-bromo-3-carboxamido-2,8-dioxo-6-methyl-10-nitro-4-(p-nitrophenyl)2,8-dihydropyran(3,2g)(1) benzopyran. Mice were injected subcutaneously (0.75 mg/mouse) with each of the compounds for three successive days, then each animal was exposed to 100 Schistosoma mansoni cercariae. The effect on the humoral immune response was detected by measuring immunoglbulin G (IgG) levels using enzyme-linked immunosorbent assay (ELISA) against E. coli lysate, soluble worm antigen preparation (SWAP) and cancer bladder tissue homogenates. The reactivity of IgG to E. coli lysate was measured in sera of treated mice before and after infection. However, for SWAP and cancer tissue homogenates the IgG was measured only after infection. Mice given compounds 2, 3 and 4 showed a concentration dependent increase in IgG level against E. coli lysate as compared to untreated uninfected mice. Animals given compounds 3 and 4 followed by S. mansoni infection showed a significant increase (p< 0.05) in IgG level against the same antigen. Moreover, compounds 1, 2 and 4 significantly (p < 0.05) stimulated IgG production when measured against SWAP. Compounds 2, 3 and 4 induced a significant (p < 0.05) IgG response to cancer bladder tissue homogenates as compared to infected control mice. At the cellular level, treatment with compounds 1, 2, 3 and 4 caused a significant increase (p < 0.05) in the mean percentage of CD4+-T cells as compared with normal control, whereas, compounds 1, 2 and 3 stimulated a significant increase (p < 0.05) in the mean percentage of CD8+-T cells. Six weeks post-infection compounds 3 and 4 induced a significant stimulation (p< 0.05) in the mean number of both CD4+ and CD8+-T cells. The study showed that the compounds used have an immunomodulatory effect at both humoral and cellular levels.


Inference of gene regulatory networks using boolean-network inference methods.
The modeling of genetic networks especially from microarray and related data has become an important aspect of the biosciences. This review takes a fresh look at a specific family of models used for constructing genetic networks, the so-called Boolean networks. The review outlines the various different types of Boolean network developed to date, from the original Random Boolean Network to the current Probabilistic Boolean Network. In addition, some of the different inference methods available to infer these genetic networks are also examined. Where possible, particular attention is paid to input requirements as well as the efficiency, advantages and drawbacks of each method. Though the Boolean network model is one of many models available for network inference today, it is well established and remains a topic of considerable interest in the field of genetic network inference. Hybrids of Boolean networks with other approaches may well be the way forward in inferring the most informative networks.


New complete mitochondrial genome of the Perccottus glenii (Perciformes, Odontobutidae): additional non-coding region.
Perccottus glenii is a species of freshwater sleeper native to the Russian Far East, north-eastern China, and the northern part of the Korean Penninsula with introduced populations in other regions of Eurasia. In this study, a new complete mitochondrial genome of Perccottus glenii was reported. The circular genome is 16,510 bp in length and consists of 13 protein-coding genes, 22 tRNA genes, 2 ribosomal RNA genes, and 1 control region. Except the origin of the light strand replication (OL), an additional non-coding region was present between ND6 and tRNA-Glu in the Light strand. The overall nucleotide composition was 30.5% A, 29.2% T, 24.4% C and 15.9% G, with an A + T bias of 59.7%. The gene composition and the structural arrangement of the P. glenii complete mtDNA were identical to most of the other vertebrates. The molecular data here we presented could play a useful role to study the evolutionary relationships and population genetics of Odontobutidae fish.


Father-child relationships from the preschool years through mid-adolescence.
In this study, we examined variations in fathering and father-child relationships from the children's preschool years through mid-adolescence. One hundred seventy-seven fathers with first-born children ages 4, 8, 12, and 16 years responded to five sets of questionnaires tapping four domains of childrearing: practices, attitudes, parental role involvement, and role satisfaction. A multivariate analysis of variance identified significant variability among the four age groups in fathers' use of acceptance in childrearing practices, role involvement (frequency and task sharing), satisfaction with paternal role performance, and attitudes about the modifiability of child behavior. The results contribute new information about the nature of fathering throughout the childhood years and adolescence and provide additional support for the view of parenting as dynamic and responsive to the developmental level and gender-related characteristics of the child.


FTIR Spectrum of the nu4 Band of DCOOD.
The FTIR spectrum of the nu4 band of deuterated formic acid (DCOOD) has been measured with a resolution of 0.004 cm-1 in the frequency range of 1120 to 1220 cm-1. A total of 1866 assigned transitions have been analyzed and fitted using a Watson's A-reduced Hamiltonian in the Ir representation to derive rovibrational constants for the upper state (v4 = 1) with a standard deviation of 0.00036 cm-1. In the course of the analysis, the constants for the ground state were improved by a simultaneous fit of microwave frequencies and combination differences from the infrared measurements. Due to the relatively unperturbed nature of the band, the constants can be used to accurately calculate the infrared line positions for the whole band. Although the band is a hybrid type A and B, only a-type transitions were strong enough to be observed. The band center is at 1170.79980 +/- 0.00002 cm-1. Copyright 1999 Academic Press.


[Mexican families in their homeland and in exile].
"The present study takes advantage of the Mexican and American census simultaneity in Spring 1990 to compare the Mexican populations according to their migratory status. The analysis of their composition by age and by sex is completed by an estimation of the undercount of migrants omitted by these statistics.... The fertility of the Mexican immigrants is compared to that of the country of origin and to that of Mexican Americans so as to specify changes induced by the exile. But one of the most interesting mutations deals with the recomposition of the migrant's family in the U.S.: units of residence gain in complexity by the extended integration of relatives or individuals that do not belong to the nuclear family." (SUMMARY IN ENG AND SPA)