Clinicopathological implication of cripto expression in early stage invasive cervical carcinomas.
This study evaluates the expression of cripto (CR-1) protein in matched sets of non-neoplastic cervical epithelium, primary cervical carcinoma and metastatic tumours in the lymph nodes to investigate its role in uterine cervical cancer development and progression. Ninety-four primary cervical carcinomas in an early clinical stage and having the same surgical treatment modality were analysed. Immunoreactivity in the primary tumour was compared with that of non-neoplastic cervical epithelium and metastatic lymph nodes. The conventional clinicopathological prognostic variables for cervical carcinomas such as grade, tumour size, depth of invasion, parametrial and endometrial extension, lymphovascular space involvement and lymph node metastasis status were also compared with CR-1 expression of the primary tumour. Strong CR-1 immunopositivity was significantly correlated with tumour size and lymphovascular space involvement (P < 0.05). Furthermore, a significant relationship was found between CR-1 immunoreactivity and endometrial extension as well as parametrial involvement (P < 0.05). Interestingly, the CR-1 expression level was increased in metastatic lymph nodes compared with their primary tumours. These results suggest that CR-1 may contribute to disease progression in cervical carcinomas.


An exploration of strategies used by dressage horses to control moments around the center of mass when performing passage.
Locomotion results from the generation of ground reaction forces (GRF) that cause translations of the center of mass (COM) and generate moments that rotate the body around the COM. The trot is a diagonally-synchronized gait performed by horses at intermediate locomotor speeds. Passage is a variant of the trot performed by highly-trained dressage horses. It is distinguished from trot by having a slow speed of progression combined with great animation of the limbs in the swing phase. The slow speed of passage challenges the horse's ability to control the sagittal-plane moments around the COM. Footfall patterns and peak GRF are known to differ between passage and trot, but their effects on balance management, which we define here as the ability to control nose-up/nose-down pitching moments around the horse's COM to maintain a state of equilibrium, are not known. The objective was to investigate which biomechanical variables influence pitching moments around the COM in passage. Three highly-trained dressage horses were captured by a 10-camera motion analysis system (120 Hz) as they were ridden in passage over four force platforms (960 Hz). A full-body marker set was used to track the horse's COM and measure balance variables including total body center of pressure (COP), pitching moments, diagonal dissociation timing, peak force production, limb protraction-retraction, and trunk posture. A total of twenty passage steps were extracted and partial correlation (accounting for horse) was used to investigate significant (P < 0.05) relationships between variables. Hindlimb mean protraction-retraction correlated significantly with peak hindlimb propulsive forces (R = 0.821; P < 0.01), mean pitching moments (R = 0.546, P = 0.016), trunk range of motion, COM craniocaudal location and diagonal dissociation time (P < 0.05). Pitching moments around the COM were controlled by a combination of kinematic and kinetic adjustments that involve coordinated changes in GRF magnitudes, GRF distribution between the diagonal limb pairs, and the moment arms of the vertical GRFs. The moment arms depend on hoof placements relative to the COM, which were adjusted by changing limb protraction-retraction angles. Nose-up pitching moments could also be increased by providing a larger hindlimb propulsive GRF.


The multidomain protein Brpf1 binds histones and is required for Hox gene expression and segmental identity.
The Trithorax group (TrxG) is composed of diverse, evolutionary conserved proteins that form chromatin-associated complexes accounting for epigenetic transcriptional memory. However, the molecular mechanisms by which particular loci are marked for reactivation after mitosis are only partially understood. Here, based on genetic analyses in zebrafish, we identify the multidomain protein Brpf1 as a novel TrxG member with a central role during development. brpf1 mutants display anterior transformations of pharyngeal arches due to progressive loss of anterior Hox gene expression. Brpf1 functions in association with the histone acetyltransferase Moz (Myst3), an interaction mediated by the N-terminal domain of Brpf1, and promotes histone acetylation in vivo. Brpf1 recruits Moz to distinct sites of active chromatin and remains at chromosomes during mitosis, mediated by direct histone binding of its bromodomain, which has a preference for acetylated histones, and its PWWP domain, which binds histones independently of their acetylation status. This is the first demonstration of histone binding for PWWP domains. Mutant analyses further show that the PWWP domain is absolutely essential for Brpf1 function in vivo. We conclude that Brpf1, coordinated by its particular set of domains, acts by multiple mechanisms to mediate Moz-dependent histone acetylation and to mark Hox genes for maintained expression throughout vertebrate development.


β-lactams against emerging 'superbugs': progress and pitfalls.
Bacterial resistance to antimicrobial agents is an ever-growing problem. So-called 'superbugs', such as multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa harboring multiple resistance determinants, including extended-spectrum β-lactamases, carbapenemases, efflux pumps and downregulated outer-membrane proteins or porins, are becoming more prevalent in hospital, intensive and long-term care settings. Enterobacteriaceae are also acquiring a myriad of β-lactamases, such as class A and D carbapenemases, and plasmid-borne class C cephalosporinases. Gram-positive superbugs, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate or heteroglycopeptide-intermediate S. aureus, vancomycin-resistant S. aureus and penicillin-resistant Streptococcus pneumoniae (PRSP), are problematic pathogens, both in the hospital and in the community (e.g., community-acquired MRSA and PRSP). β-lactam antibiotics remain among the most effective and safest anti-infectives in use, although their utility is being severely challenged by these superbugs. This review will discuss aspects of resistance seen in these pathogens and will review some of the newer β-lactam agents, both investigational and in clinical use, that target these superbugs.


Optimization of the interferon assay using inhibition of Semliki forest virus-ribonucleic acid synthesis.
The method for assaying chicken interferon by its inhibition of viral ribonucleic acid (RNA) synthesis was optimized for the chicken embryo fibroblast-Semliki Forest virus (SFV) system, with respect to time, multiplicity of infection, and addition of actinomycin D and (3)H-uridine. Incorporation of (3)H into viral RNA is reproducible, and amounts to 10(4) to 2 x 10(4) counts per min per uninhibited culture per 1 muCi per 6 hr. The assay may be carried out in less than 1 day and is sensitive (0.05 units/ml) and exact (+/-20% of the mean titers on different days); it can be used for purification procedures as well.


iPSC-derived hypoimmunogenic tissue resident memory T cells mediate robust anti-tumor activity against cervical cancer.
Functionally rejuvenated human papilloma virus-specific cytotoxic T lymphocytes (HPV-rejTs) generated from induced pluripotent stem cells robustly suppress cervical cancer. However, autologous rejT generation is time consuming, leading to difficulty in treating patients with advanced cancer. Although use of allogeneic HPV-rejTs can obviate this, the major obstacle is rejection by the patient immune system. To overcome this, we develop HLA-A24&-E dual integrated HPV-rejTs after erasing HLA class I antigens. These rejTs effectively suppress recipient immune rejection while maintaining more robust cytotoxicity than original cytotoxic T lymphocytes. Single-cell RNA sequencing performed to gain deeper insights reveal that HPV-rejTs are highly enriched with tissue resident memory T cells, which enhance cytotoxicity against cervical cancer through TGFβR signaling, with increased CD103 expression. Genes associated with the immunological synapse also are upregulated, suggesting that these features promote stronger activation of T cell receptor (TCR) and increased TCR-mediated target cell death. We believe that our work will contribute to feasible "off-the-shelf" T cell therapy with robust anti-cervical cancer effects.


Identification of nucleotide substitutions necessary for trans-activation of mariner transposable elements in Drosophila: analysis of naturally occurring elements.
Six copies of the mariner element from the genomes of Drosophila mauritiana and Drosophila simulans were chosen at random for DNA sequencing and functional analysis and compared with the highly active element Mos1 and the inactive element peach. All elements were 1286 base pairs in length, but among them there were 18 nucleotide differences. As assayed in Drosophila melanogaster, three of the elements were apparently nonfunctional, two were marginally functional, and one had moderate activity that could be greatly increased depending on the position of the element in the genome. Both molecular (site-directed mutagenesis) and evolutionary (cladistic analysis) techniques were used to analyze the functional effects of nucleotide substitutions. The nucleotide sequence of the element is the primary determinant of function, though the activity level of elements is profoundly influenced by position effects. Cladistic analysis of the sequences has identified a T----A transversion at position 1203 (resulting in a Phe----Leu amino acid replacement in the putative transposase) as being primarily responsible for the low activity of the barely functional elements. Use of the sequences from the more distantly related species, Drosophila yakuba and Drosophila teissieri, as outside reference species, indicates that functional mariner elements are ancestral and argues against their origination by a novel mutation or by recombination among nonfunctional elements.


A systematic review of screening instruments for depression for use in antenatal services in low resource settings.
In low resource settings, short, valid and reliable instruments with good high sensitivity and specificity are essential for the screening of depression in antenatal care. A review of published evidence on screening instruments for depression for use in antenatal services in low resource settings was conducted. The aim of this review was to appraise the best available evidence on screening instruments suitable for detecting depression in antenatal care in low resource settings. Searching, selection, quality assessment, and data abstraction was done by two reviewers. ScienceDirect, CINAHL, MEDLINE, PubMed, SABINET and PsychARTICLES databases were searched using relevant search terms. Retrieved studies were evaluated for relevancy (whether psychometric data were reported) and quality. Data were synthesised and sensitivity and specificity of instruments were pooled using forest plots. Eleven articles were included in the review. The methodological quality ranged from adequate to excellent. The review found 7 tools with varying levels of accuracy, sensitivity and specificity, including the Edinburgh Postnatal Depression Scale, Beck Depression Index, Centre for Epidemiologic Studies Depression Scale 20, Hamilton Rating Scale for Depression, Hopkins Symptoms Checklist-25, Kessler Psychological Distress Scale and Self-Reporting Questionnaire. The Edinburgh Postnatal Depression Scale was most common and had the highest level of accuracy (AUC = .965) and sensitivity. This review suggests that the Edinburgh Postnatal Depression Scale can be a suitable instrument of preference for screening antenatal depression in low resource settings because of the reported level of accuracy, sensitivity and specificity. CRD42015020316 .


Use of anti-neoepitope antibodies for the analysis of degradative events in cartilage and the molecular basis for neoepitope specificity.
Degradation of the cartilage proteoglycan, aggrecan, is an essential aspect of normal growth and development, and of joint pathology. The roles of different proteolytic enzymes in this process can be determined from the sites of cleavage in the aggrecan core protein, which generates novel termini (neoepitopes). Antibodies specific for the different neoepitopes generated by such cleavage events provide powerful tools with which to analyse these processes. The same approach can be used to differentiate the processed, active forms of proteases from their inactive pro-forms. Since the proteolytic processing of these enzymes requires the removal of the inhibitory pro-region, it also results in the generation of N-terminal neoepitopes. Using the newborn rat long bone as a model system, it was shown that the active form of ADAMTS-4 [ADAM (a disintegrin and metalloproteinase) with thrombospondin motifs-4], but not ADAMTS-5, co-localizes with the aggrecan cleavage neoepitopes known to be produced by this metalloproteinase. Thus, in long bone growth, aggrecan turnover seems to be dependent on ADAMTS-4 activity. To demonstrate the molecular basis of the specificity of anti-neoepitope antibodies, the Fv region of a monoclonal antibody specific for a neoepitope generated by the ADAMTS-4-mediated cleavage of aggrecan has been modelled and the binding of the peptide epitope simulated. In the docked structure, the N-terminus of the peptide antigen is clearly buried in the binding-site cavity. The absence of an open cleft makes it impossible for the intact substrate to pass through the binding site, providing a rationale for the specificity of this class of antibodies.


MAN UNDER PRESSURE.
Current achievements in environments at pressures higher than atmospheric are reviewed, ranging from the uses of hyperbaric oxygen for treatment to the concept of residence at high pressure for extended Continental Shelf exploration and very deep caisson work.A case is made for the use of high oxygen pressures in the treatment of hypoxias of acute onset, of certain infections, and as an adjunct to radiotherapy. Achievement of the desired high tissue tensions of oxygen while avoiding toxicity requires careful choice of both pressure and duration of exposure.Man has successfully dived to 1000 feet in the sea, and has remained for weeks at high pressures. Adequate prophylactic decompression remains a major problem, since current recompression procedures are to a large extent empirically derived. There are grounds for expecting improved prophylactic and therapeutic procedures when present studies are completed.


Models for material failure and deformation.
Simple computer models have been used to investigate a variety of pattern formation processes associated with material failure and deformation. These models reproduce surprisingly well the characteristic morphologies observed in a wide range of real systems. They provide a sound basis for the development of more realistic models that can be used to develop a better understanding of the mechanical properties of real materials. The present algorithms are adequate for some purposes, but substantial improvements are needed if simulation results are to make a major contribution to our theoretical understanding of the asymptotic fractal scaling and universality properties of patterns generated by failure and deformation phenomena.


Dermal Exposure to Hazardous Chemicals in Baby Diapers: A Re-Evaluation of the Quantitative Health Risk Assessment Conducted by The French Agency for Food, Environmental and Occupational Health and Safety (ANSES).
In January 2019, the French Agency for Food, Environmental and Occupational Health and Safety (ANSES) published an opinion on risks related to the presence of hazardous chemicals in infant diapers. ANSES found that health reference values were largely exceeded for polycyclic aromatic hydrocarbons (PAHs), dioxins (PCCD/Fs) and dioxin-like polychlorobiphenyls (DL-PCBs). The levels of formaldehyde and some fragrances were also considered potentially unsafe. Therefore, ANSES concluded that actions have to be taken to restrict levels of these contaminants in diapers. Under the exposure scenario deemed the most reliable by ANSES, estimates of cancer risks of the most potent PAHs detected in diapers exceeded 10-3 and hazard quotients for neurobehavioral effects attained values up to 66. Regarding dioxins and DL-PCBs, ANSES derived a hazard quotient of 12 for the risk of decreased sperm count at adult age. The aim of this study was to examine whether the exposure and risk assessment conducted by ANSES contained potential flaws that could explain such a high exceedance of health reference values. This study also put into perspective the exposure from diapers with that from breast milk whose benefits for children's health are undisputable despite contamination by PAHs, dioxins and DL-PCBS.


Enhanced surveillance of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines in pregnancy in the Vaccine Adverse Event Reporting System (VAERS), 2011-2015.
In October 2011, the Advisory Committee on Immunization Practices (ACIP) issued updated recommendations that all pregnant women routinely receive a dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine. We characterized reports to the Vaccine Adverse Event Reporting System (VAERS) in pregnant women who received Tdap after this updated recommendation (2011-2015) and compared the pattern of adverse events (AEs) with the period before the updated recommendation (2005-2010). We searched the VAERS database for reports of AEs in pregnant women who received Tdap vaccine after the routine recommendation (11/01/2011-6/30/2015) and compared it to published data before the routine Tdap recommendation (01/01/2005-06/30/2010). We conducted clinical review of reports and available medical records. The clinical pattern of reports in the post-recommendation period was compared with the pattern before the routine Tdap recommendation. We found 392 reports of Tdap vaccination after the routine recommendation. One neonatal death but no maternal deaths were reported. No maternal or neonatal deaths were reported before the recommendation. We observed an increase in proportion of reports for stillbirths (1.5-2.8%) and injection site reactions/arm pain (4.5-11.9%) after the recommendation compared to the period before the routine recommendation for Tdap during pregnancy. We noted a decrease in reports of spontaneous abortion (16.7-1%). After the 2011 Tdap recommendation, in most reports, vaccination (79%) occurred during the third trimester compared to 4% before the 2011 Tdap recommendation. Twenty-six reports of repeat Tdap were received in VAERS; 13 did not report an AE. One medical facility accounted for 27% of all submitted reports. No new or unexpected vaccine AEs were noted among pregnant women who received Tdap after routine recommendations for maternal Tdap vaccination. Changes in reporting patterns would be expected, given the broader use of Tdap in pregnant women in the third trimester.


Tuberculosis in Bissau: incidence and risk factors in an urban community in sub-Saharan Africa.
Despite the long history of tuberculosis (TB) research, population-based studies from developing countries are rare. In a prospective community study in Bissau, the capital of Guinea-Bissau, we assessed the impact of demographic, socioeconomic and cultural risk factors on active TB. A surveillance system in four districts of the capital identified 247 adult (>or=15 years) cases of intrathoracic TB between May 1996 and June 1998. Risk factors were evaluated comparing cases with the 25,189 adults living in the area in May 1997. The incidence of intrathoracic TB in the adult population was 471 per 100 000 person-years. Significant risk factors in a multivariate analysis were increasing age (P < 0.0001), male sex (odds ratio [OR] = 2.58, 95% CI: 1.85, 3.60), ethnic group other than the largest group (Pepel) (OR = 1.64, 95% CI: 1.20, 2.22), adult crowding (OR = 1.68, 95% CI: 1.18, 2.39 for >2 adults in household), and poor quality of housing (OR = 1.66, 95% CI: 1.24, 2.22). Household type was important; adults living alone or with adults of their own sex only, had a higher risk of developing TB than households with husband and wife present, the adjusted OR being 1.76 (95% CI: 1.11, 2.78) for male households and 3.80 (95% CI: 1.69, 8.56) for female households. In a multivariate analysis excluding household type, child crowding was a protective factor, the OR being 0.68 (95% CI: 0.51, 0.90) for households with >2 children per household. Bissau has a very high incidence of intrathoracic TB. Human immunodeficiency virus (HIV), increasing age, male sex, ethnicity, adult crowding, family structure, and poor housing conditions were independent risk factors for TB. Apart from HIV prevention, TB control programmes need to emphasize risk factors such as socioeconomic inequality, ethnic differences, crowding, and gender.


Healthy Ageing: Raising Awareness of Inequalities, Determinants, and What Could Be Done to Improve Health Equity.
Social and scientific discourses on healthy ageing and on health equity are increasingly available, yet from a global perspective limited conceptual and analytical work connecting both has been published. This review was done to inform the WHO World Report on Ageing and Health and to inform and encourage further work addressing both healthy aging and equity. We conducted an extensive literature review on the overlap between both topics, privileging publications from 2005 onward, from low-, middle-, and high-income countries. We also reviewed evidence generated around the WHO Commission on Social Determinants of Health, applicable to ageing and health across the life course. Based on data from 194 countries, we highlight differences in older adults' health and consider three issues: First, multilevel factors that contribute to differences in healthy ageing, across contexts; second, policies or potential entry points for action that could serve to reduce unfair differences (health inequities); and third, new research areas to address the cause of persistent inequities and gaps in evidence on what can be done to increase healthy ageing and health equity. Each of these areas warrant in depth analysis and synthesis, whereas this article presents an overview for further consideration and action.


[Comparative study on association between femoral head size and linear wear rate of highly cross-linked polyethylene liner].
To investigate the effects of the femoral head size on the linear wear rate of highly cross-linked polyethylene (HXLPE) liner in total hip arthroplasty (THA). A retrospective analysis was performed on the clinical data of 41 patients (43 hips) who underwent primary THA with HXLPE liner and different sizes of femoral heads between January 2004 and December 2007 for hip diseases. There were 22 males (23 hips) and 19 females (20 hips) with a mean age of 60.2 years (range, 35-89 years), including femoral neck fracture (26 hips), avascular necrosis of femoral head (8 hips), osteoarthritis (5 hips), rheumatoid arthritis (2 hips), and congenital hip dysplasia (2 hips). According to the size of the femoral head, the patients were divided into 2 groups: standard head size (26 and 28 mm) was used in 25 cases (26 hips, group A) and big head size (32, 36, and 40 mm) in 16 cases (17 hips, group B). The cumulative penetration of the femoral head, linear wear rate, and effectiveness were evaluated and compared between 2 groups. All the incisions healed by first intention, no complications of infection, deep vein thrombosis, or nerve injury occurred. The patients were followed up 5-9 years (mean, 5.7 years). No two-stage revision was needed. Harris score was significantly improved at 3 months, 6 months, and 1, 2, 3, 4, and 5 years after operation when compared with preoperative score in each group (P < 0.05), but no significant difference was found between different time points after operation in 2 groups (P > 0.05), and between 2 groups at each time point (P > 0.05). Acetabular abduction angle was (31.4 ± 3.8)° in group A and (32.3 ± 4.1)° in group B, showing no significant difference (t = 0.482, P = 0.621). At last follow-up, no radiographic or clinical loosening was observed in each group. At 5 years after operation, X-ray results of acetabular components showed radiolucent line (< 1 mm) in 1 case (1 hip) and 1 case (1 hip) of 2 groups respectively; but X-ray results of femoral components showed no radiolucent line. There was no significant difference in the cumulative penetration of the femoral head between 2 groups at 1, 2, 3, 4, and 5 years after operation (P > 0.05). The linear wear rate was (0.026 ± 0.007) mm/year in group A and (0.025 ± 0.007) mm/year in group B, showing no significant difference between 2 groups (t = -0.708, P = 0.483). No association is found between femoral head size and the linear wear rate of HXLPE liner. It is an ideal interface of THA because of its low linear wear rate.


Purification and characterization of N-ethylmaleimide-insensitive phosphatidic acid phosphohydrolase (PAP2) from rat liver.
N-Ethylmaleimide-insensitive phosphatidic acid phosphohydrolase (PAP; EC 126.96.36.199) was purified 5900-fold from rat liver. The enzyme was solubilized from membranes with octylglucoside, fractionated with (NH4)2SO4, and purified in the presence of Triton X-100 by chromatography on Sephacryl S300, hydroxyapatite, heparin-Sepharose and Affi-Gel Blue. Silver-stained SDS/PAGE indicated that the enzyme was an 83 kDa polypeptide. Sephacryl S-300 gel filtration also produced a second peak of enzyme activity, which was eluted from all of the chromatography columns at a different position from the purified enzyme. SDS/PAGE indicated that it contained three polypeptides (83 kDa, 54 kDa and 34 kDa), and gel filtration suggested that it was not an aggregate of the purified enzyme. Both forms were sensitive to inhibition by amphiphilic amines, Mn2+ and Zn2+, but not by N-ethylmaleimide. Purified PAP required detergent for activity, but was not activated by Mg2+, fatty acids or phospholipids. The enzyme was able to dephosphorylate lysophosphatidic acid or phosphatidic acid, and was inhibited by diacylglycerol and monoacylglycerol. No evidence was obtained for regulation of PAP by reversible phosphorylation.


Life after pelvic organ prolapse surgery: a qualitative study in Amhara region, Ethiopia.
Women living in resource constrained settings often have limited knowledge of and access to surgical treatment for pelvic organ prolapse. Additionally, little is known about experiences during recovery periods or about the reintegration process for women who do gain access to medical services, including surgery. This study aimed to explore women's experiences related to recovery and reintegration after free surgical treatment for pelvic organ prolapse in a resource-constrained setting. The study had a qualitative design and used in-depth interviews in the data collection with a purposive sample of 25 participants, including 12 women with pelvic organ prolapse. Recruitment took place at the University of Gondar Hospital, Ethiopia, where women with pelvic organ prolapse had been admitted for free surgical treatment. In-depth interviews were carried out with women at the hospital prior to surgery and in their homes 5-9 months following surgery. Interviews were also conducted with health-care providers (8), representatives from relevant organizations (3), and health authorities (2). The fieldwork was carried out in close collaboration with a local female interpreter. The majority of the women experienced a transformation after prolapse surgery. They went from a life dominated by fear of disclosure, discrimination, and divorce due to what was perceived as a shameful and strongly prohibitive condition both physically and socially, to a life of gradually regained physical health and reintegration into a social life. The strong mobilization of family-networks for most of the women facilitated work-related help and social support during the immediate post-surgery period as well as on a long-term basis. The women with less extensive social networks expressed greater challenges, and some struggled to meet their basic needs. All the women openly disclosed their health condition after surgery, and several actively engaged in creating awareness about the condition. Free surgical treatment substantially improved the health and social life for most of the study participants. The impact of the surgery extended to the communities in which the women lived through increased openness and awareness and thus had the potential to ensure increased disclosure among other women who suffer from this treatable condition.


Study on the Oxygen Enrichment Effect of Individual Oxygen-Supply Device in a Tunnel of Plateau Mine.
Complex characteristics of the plateau environment such as low oxygen content seriously restrict the exploitation of abundant mineral resources in plateau areas. To regulate the hypoxia environment and improve the comfort of workers engaged in intense physical labor like tunnel excavation operations in plateau mines, an individual oxygen-supply device for tunnel of plateau mine was proposed to create local oxygen enrichment in the area around the human nose. The Computational Fluid Dynamics (CFD) method was used to judge the application's effect of the individual oxygen-supply device in plateau mine, revealing the oxygen diffusion law under the influence of different oxygen enrichment factors. The orthogonal design and range analysis were used to measure the degree of influence of major factors such as oxygen-supply velocity, oxygen-supply concentration, and tunnel airflow velocity. The results demonstrate that the oxygen mass fraction of the air inhaled by the human had a positive correlation exponential function, a positive correlation linear function, and a negative correlation exponential function, respectively, concerning oxygen-supply velocity, oxygen-supply concentration, and tunnel airflow velocity. The range analysis revealed that the major influencing factors of oxygen enrichment in the tunnel of the plateau mine were, in a descending sequence, as follows: oxygen-supply concentration, tunnel airflow velocity, and oxygen-supply velocity, and the corresponding ranges were 2.86, 2.63, and 1.83, respectively. The individual oxygen-supply device achieved the best oxygen enrichment effect when the oxygen-supply velocity was 5 m/s, the oxygen-supply concentration was 60%, and the tunnel airflow velocity was 0.2 m/s, which increased the oxygen mass fraction of air inhaled by the human to 30.42%. This study has a positive guiding significance for the improvement of the respiration environment in the tunnel of plateau mine.


Congenital joint laxity and disproportionate dwarfism in a herd of beef cattle.
Three calves from a herd of beef cattle were examined because of disproportionate dwarfism and excessive extension of metacarpophalangeal and metatarsophalangeal joints. Abnormalities had been noticed at birth, 1 to 6 days earlier. A thorough herd investigation revealed that 16 calves born to 70 multiparous cows were affected during the calving season. The condition did not adversely affect calf survival. Affected calves had limbs that were disproportionally short, compared with their trunk size, and wide epiphyses of the femurs and humeri. Radiographic evaluation revealed incomplete maturation of carpal and tarsal bones and incomplete maturation and abnormal flaring of epiphyses of the short humeri and femurs. Histologic findings were consistent with chondrodystrophy. This disorder had not been seen in the herd in previous years and was traced to feeding of dry, spoiled silage to the dams during midgestation. Covering the silage prevented problems in the subsequent year.


Poison ivy dermatitis.
Eruptions caused by poison ivy (see Cover) and related plants are almost always a form of allergic contact dermatitis. Usually they can be readily recognized because of their characteristic streak- or line-like appearance. They usually clear within one to three weeks unless there is continued exposure to the allergen. Local treatment suffices in mild to moderate cases, but in more severe cases systemic corticosteroids can be added.


Osteogenesis imperfecta type V: clinical and radiographic manifestations in mutation confirmed patients.
Osteogenesis imperfecta (OI) type V is a specific OI phenotype with interosseous membrane calcification of the forearm and hyperplastic callus formation as typical features. The causative gene mutation for OI type V has been recently discovered. The purpose of this report is to review the clinical and radiographic characteristics of mutation confirmed OI type V in detail. Sixteen (nine familial and seven sporadic) patients were enrolled in the study. Blue sclera and dentinogenesis imperfecta were not evident in any patient. However, hypodontia in the permanent teeth, ectopic eruption, and short roots in molars were additionally observed in 11 patients. Of the radiographic abnormalities, cortical thickening and bony excrescence of interosseous margin of the ulna was the most common finding, followed by overgrowth of the olecranon and/or coronoid process of the ulna. Slender ribs and sloping of the posterior ribs with or without fractures were also a consistent finding. Hyperplastic callus was detected in 75% of patients and was commonly encountered at the femur. Heterotopic ossification in the muscles and tendon insertion sites were noted in four patients, which resulted in bony ankylosis or contracture of joints. The current study confirms common clinical and radiographic findings of OI type V and reports additional phenotypic information. These observations provide clues to recognize OI type V more promptly and guide to direct targeted molecular study. © 2013 Wiley Periodicals, Inc.


Basic Concepts of Contrast Injection Protocols for Coronary Computed Tomography Angiography.
Coronary Computed Tomography Angiography (CTA) has become one of the most important diagnostic imaging modalities for the evaluation of coronary artery diseases. During coronary computed CTA, sufficient vascular enhancement is essential for the accurate detection and evaluation of lesions in the coronary arteries. To obtain optimal contrast enhancement and perform appropriate clinical coronary CTA, physicians, radiologists, and radiology technologists should acquire a basic knowledge of contrast injection protocols. This review article summarizes the basic concepts of contrast injection protocols for coronary CTA.


Market concentration, supply, quality and prices paid by local authorities in the English care home market.
We investigate the impact of exogenous local conditions which favor high market concentration on supply, price and quality in local markets for care homes for older people in England. We extend the existing literature in: (i) considering supply capacity as a market outcome alongside price and quality; (ii) taking account of the chain structure of care home supply and differences between the nursing home and residential care home sectors; (iii) using an econometric approach based on reduced form relationships that treats market concentration as a jointly determined outcome of a complex market. We find that areas susceptible to a high degree of market concentration tend to have greatly restricted supply of care home places and (to a lesser extent) a higher average public cost, than areas susceptible to low degree of market concentration. There is no significant evidence that conditions favoring high market concentration affect average care home quality.


Nuclear and cytoplasmic lectin receptor sites in rat Py1a osteoblasts.
The intracellular distribution of lectin receptor sites was studied in the rat Pyla osteoblasts using immunofluorescence at the confocal microscopy level. This immortalized cell line was found to represent a satisfactory model to study the occurrence and distribution of sugar moieties. Our data showed distinct affinity patterns of lectins recognizing different terminal or internal sugar residues. For some lectins, the binding patterns appeared to be cell cycle-independent, whereas for PNA the cell cycle greatly influenced the nuclear binding. By combining lectin affinity with sialidase degradation and alcoholic saponification the sialic acid acceptor sugars and derivatives were also visualized. In particular, glycoconjugates with sialic acids linked to beta-galactose, and mainly C4 acetylated, were located in the cytoplasm, while glycoconjugates characterized by sialic acids linked to alpha-N-acetylgalactosamine, and devoid of acetyl groups at C4, were almost exclusively found in the nucleus. The comparison of lectin affinities, with and without prior glycosidase digestions, allowed us to gain further insight into the chemical composition of glycoconjugates that act as the lectin receptor sites that appeared to belong to O- and N-linked glycoconjugates. The use of additional enzymatic treatments were useful to better establish the localization of nuclear receptor sites and results were compared with previous studies about endogenous and exogenous lectins in an attempt to reconcile the association of lectins and sugars within the nucleus and their possible involvement in modulation of cell proliferation and/or response to chemical signals. The above digestions also provided information about the cytoplasmic binding patterns.


Feedback consistency effects in visual and auditory word recognition: where do we stand after more than a decade?
The role of phonology-to-spelling consistency (i.e., feedback consistency) was investigated in 3 lexical decision experiments in both the visual and auditory modalities in French and English. No evidence for a feedback consistency effect was found in the visual modality, either in English or in French, despite the fact that consistency was manipulated for different kinds of units (onsets and rimes). In contrast, robust feedback consistency effects were obtained in the auditory lexical decision task in both English and French when exactly the same items that produced a null effect in the visual modality were used. Neural network simulations are presented to show that previous demonstrations of feedback consistency effects in the visual modality can be simulated with a model that is not sensitive to feedback consistency, suggesting that these effects might have come from various confounds. These simulations, together with the authors' results, suggest that there are no feedback consistency effects in the visual modality. In contrast, such effects are clearly present in the auditory modality. Given that orthographic information is absent from current models of spoken word recognition, the present findings present a major challenge to these models.


Genetic control of maize shoot apical meristem architecture.
The shoot apical meristem contains a pool of undifferentiated stem cells and generates all above-ground organs of the plant. During vegetative growth, cells differentiate from the meristem to initiate leaves while the pool of meristematic cells is preserved; this balance is determined in part by genetic regulatory mechanisms. To assess vegetative meristem growth and genetic control in Zea mays, we investigated its morphology at multiple time points and identified three stages of growth. We measured meristem height, width, plastochron internode length, and associated traits from 86 individuals of the intermated B73 × Mo17 recombinant inbred line population. For meristem height-related traits, the parents exhibited markedly different phenotypes, with B73 being very tall, Mo17 short, and the population distributed between. In the outer cell layer, differences appeared to be related to number of cells rather than cell size. In contrast, B73 and Mo17 were similar in meristem width traits and plastochron internode length, with transgressive segregation in the population. Multiple loci (6-9 for each trait) were mapped, indicating meristem architecture is controlled by many regions; none of these coincided with previously described mutants impacting meristem development. Major loci for height and width explaining 16% and 19% of the variation were identified on chromosomes 5 and 8, respectively. Significant loci for related traits frequently coincided, whereas those for unrelated traits did not overlap. With the use of three near-isogenic lines, a locus explaining 16% of the parental variation in meristem height was validated. Published expression data were leveraged to identify candidate genes in significant regions.


Application of Artificial Intelligence in Cardiovascular Imaging.
During the last two decades, as computer technology has matured and business scenarios have diversified, the scale of application of computer systems in various industries has continued to expand, resulting in a huge increase in industry data. As for the medical industry, huge unstructured data has been accumulated, so exploring how to use medical image data more effectively to efficiently complete diagnosis has an important practical impact. For a long time, China has been striving to promote the process of medical informatization, and the combination of big data and artificial intelligence and other advanced technologies in the medical field has become a hot industry and a new development trend. This paper focuses on cardiovascular diseases and uses relevant deep learning methods to realize automatic analysis and diagnosis of medical images and verify the feasibility of AI-assisted medical treatment. We have tried to achieve a complete diagnosis of cardiovascular medical imaging and localize the vulnerable lesion area. (1) We tested the classical object based on a convolutional neural network and experiment, explored the region segmentation algorithm, and showed its application scenarios in the field of medical imaging. (2) According to the data and task characteristics, we built a network model containing classification nodes and regression nodes. After the multitask joint drill, the effect of diagnosis and detection was also enhanced. In this paper, a weighted loss function mechanism is used to improve the imbalance of data between classes in medical image analysis, and the effect of the model is enhanced. (3) In the actual medical process, many medical images have the label information of high-level categories but lack the label information of low-level lesions. The proposed system exposes the possibility of lesion localization under weakly supervised conditions by taking cardiovascular imaging data to resolve these issues. Experimental results have verified that the proposed deep learning-enabled model has the capacity to resolve the aforementioned issues with minimum possible changes in the underlined infrastructure.


A Review of the Biomedical Applications of Zerumbone and the Techniques for Its Extraction from Ginger Rhizomes.
Zerumbone (ZER) is a phytochemical isolated from the subtropical Zingiberaceae family and as a natural compound it has different biomedical properties such as antioxidant, anti-inflammatory anti-proliferative activity. ZER also has effects on angiogenesis and acts as an antitumor drug in the treatment of cancer, showing selective toxicity toward various cancer cell lines. Several techniques also have been established for extraction of ZER from the rhizomes of ginger. This review paper is an overview of recent research about different extraction methods and their efficiencies, in vivo and vitro investigations of ZER and also its prominent chemopreventive properties and treatment mechanisms. Most of the studies mentioned in this review paper may be useful use as a knowledge summary to explain ZER extraction and anticancer activities, which will show a way for the development of strategies in the treatment of malignancies using ZER.


Diffusion-weighted brain imaging study of patients with clinical diagnosis of corticobasal degeneration, progressive supranuclear palsy and Parkinson's disease.
Corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) are two neurodegenerative disorders within the category of tauopathies, which must be considered in differential diagnosis of Parkinson's disease. Although specific clinical and neuroradiological features help to guide the clinician to a likely diagnosis of Parkinson's disease, CBD or PSP, differential diagnosis remains difficult. The aim of our study was to analyse apparent diffusion coefficient (ADC(ave)) maps from patients with clinical diagnosis of CBD (corticobasal syndrome, CBS), classical phenotype of PSP (Richardson's syndrome, RS) and Parkinson's disease (PD) in order to identify objective markers to discriminate between these groups. Thirteen Parkinson's disease patients, 10 RS patients, 7 CBS patients and 9 healthy volunteers were recruited and studied in a 1.5 T MR scanner. Axial diffusion-weighted images were obtained and the ADC(ave) map was generated. Regions of interest (ROIs) included mesencephalon, corpus callosum and left and right superior cerebellar peduncle (SCP), thalamus, caudate, putamen, pallidus, posterior limb of internal capsule, frontal and parietal white matter. Histograms of ADC(ave) were generated for all voxels in left and right cerebral hemispheres and in left and right deep grey matter regions separately, and the 50th percentile values (medians) were determined. The ratio of the smaller to the larger median value (symmetry ratio) was calculated for left and right hemispheres and for left and right deep grey matter regions (1 = perfect symmetry). Putaminal ADC(ave) values in CBS and RS were significantly greater than those in Parkinson's disease and healthy volunteers, but could not distinguish CBS from RS patients. In CBS patients, the values of the medians of cerebral hemispheres histograms were significantly higher than those in RS, Parkinson's disease and healthy volunteers, while the hemispheric symmetry ratio in CBS (0.968, range 0.952-0.976) was markedly reduced compared with RS (0.993, range 0.992-0.994), Parkinson's disease (0.991, range 0.988-0.993) and healthy controls (0.990, range 0.988-0.993). The hemispheric symmetry ratio differentiated CBS patients from RS and Parkinson's disease patients with a sensitivity and specificity of 100%. In RS patients, the ADC(ave) values of the SCPs were significantly greater than those in Parkinson's disease and healthy volunteers. Our findings confirm that putaminal ADC(ave) values evaluation provides a good discrimination between Parkinson's disease and atypical parkinsonisms, including RS and CBS. Furthermore, diffusion-weighted imaging, by detecting the brain microstructural correlates of the typical asymmetric signs and symptoms in CBS and the SCP involvement in RS, was shown to aid characterization and differentiation of atypical parkinsonism.


Validity and Reliability of Force-Time Characteristics Using a Portable Load Cell for the Isometric Midthigh Pull.
Pichardo, AW, Neville, J, Tinwala, F, Cronin, JB, and Brown, SR. Validity and reliability of force-time characteristics using a portable load cell for the isometric midthigh pull. J Strength Cond Res 38(1): 185-191, 2024-Many practitioners use the isometric midthigh pull (IMTP) to assess maximal strength in a safe, time-effective manner. However, expensive, stationary force plates are not always practical in a large team setting. Therefore, the purpose of this study was to establish the validity and between-session reliability of peak force, rate of force development (RFD), and impulse during an IMTP using 2 experimental protocols: a traditional fixed bar with a force plate (BarFP) and a flexible chain measured with a force plate (ChainFP) and a load cell (ChainLC). After a familiarization session, 13 resistance-trained men performed 3 trials of the BarFP condition and 3 trials of the chain-based conditions. The identical procedures were replicated twice more, with a week between each testing session. The main findings were (a) no RFD or impulse measures were found to achieve acceptable reliability across all methodological approaches and testing occasions; (b) peak force was reliable across all methods, with coefficient of variation ranging from 4.6 to 8.3%, intraclass correlation coefficient ranging from 0.94 to 0.98, and the least variability associated with the ChainLC condition; and (c) the ChainFP method was found to significantly underrepresent peak force by 4.8% (p < 0.05), with no significant differences between the ChainLC and BarFP methods. Therefore, the ChainLC would seem a valid, reliable, portable, and cost-effective alternative to force plates when assessing maximal isometric strength in the IMTP.


Allosteric inhibition of SHP2 uncovers aberrant TLR7 trafficking in aggravating psoriasis.
Psoriasis is a complex chronic inflammatory skin disease with unclear molecular mechanisms. We found that the Src homology-2 domain-containing protein tyrosine phosphatase-2 (SHP2) was highly expressed in both psoriatic patients and imiquimod (IMQ)-induced psoriasis-like mice. Also, the SHP2 allosteric inhibitor SHP099 reduced pro-inflammatory cytokine expression in PBMCs taken from psoriatic patients. Consistently, SHP099 significantly ameliorated IMQ-triggered skin inflammation in mice. Single-cell RNA sequencing of murine skin demonstrated that SHP2 inhibition impaired skin inflammation in myeloid cells, especially macrophages. Furthermore, IMQ-induced psoriasis-like skin inflammation was significantly alleviated in myeloid cells (monocytes, mature macrophages, and granulocytes)-but not dendritic cells conditional SHP2 knockout mice. Mechanistically, SHP2 promoted the trafficking of toll-like receptor 7 (TLR7) from the Golgi to the endosome in macrophages by dephosphorylating TLR7 at Tyr1024, boosting the ubiquitination of TLR7 and NF-κB-mediated skin inflammation. Importantly, Tlr7 point-mutant knock-in mice showed an attenuated psoriasis-like phenotype compared to wild-type littermates following IMQ treatment. Collectively, our findings identify SHP2 as a novel regulator of psoriasis and suggest that SHP2 inhibition may be a promising therapeutic approach for psoriatic patients.


Histopathological changes of cervical tissue in women with systemic sclerosis.
Systemic sclerosis is a connective tissue disease that can affect almost any organ of the body. The clinical aspects of systemic sclerosis on the reproductive system have been studied in large series, and an increased rate of cesarean section has been reported. For this reason, in the present study the histopathological features of cervical specimens of hysterectomyzed women with systemic sclerosis were evaluated. An increased frequency of vascular and stromal abnormalities in cervical specimens of women with systemic sclerosis were observed. Vascular medial hypertrophy, intimal thickening, and fibrosis were more often encountered in the cervical specimens of the patients with systemic sclerosis. Some of the histopathological features also showed correlation with the clinical profile of the disease. The patients with vascular medial hypertrophy in their cervical specimens were older, had a higher Rodnan score, and had longer duration of the disease. In contrast to vascular medial hypertrophy, periadventitial edema was found in the cervical specimens of the patients who were younger, had a lower Rodnan score, and had shorter duration of the disease. It was concluded that the problems that are seen in common obstetric and gynecological practices in patients with systemic sclerosis may be explained by these tissue abnormalities.


New comprehensive mathematical model for HPMC-MCC based matrices to design oral controlled release systems.
A comprehensive model with all effective phenomena in drug release such as diffusion, swelling and erosion was considered. In this work, a mathematical model was developed to describe drug release from controlled release HPMC matrices as a favorable system in pharmaceutical industries. As a novel study, the impact of the MCC presence as a filler in tablet preparation process was considered in the mathematical model. In addition, we found that the volume expansion of these polymeric matrices did not follow the ideal mixing rule and we derived an equation for estimating the volume of hydrated matrix. Furthermore, some equations were derived to estimate the parameters of model (Kerosion, Deq) as well as the change in matrix volume based on the amount of polymer and filler in formulation. This investigation gave deeper insight into underlying drug release mechanisms. According to the results, Kerosion increases linearly and Deq increases exponentially with the increase in the amount of MCC in formulation. Application of this comprehensive mathematical model enables us to predict the behavior of HPMC-MCC based matrices. Furthermore, this model is able to represent the formulation for the desired drug release profile which is useful to design new controlled release matrix as well as improving the system geometry and dimensions of tablets. The presented model was validated by two independent tests: (a) predicting the behavior of matrix with certain MCC/HPMC ratio upon exposure to the release medium; (b) designing formulation of Bupropion hydrochloride extended release tablet.


Study of Inheritance and Linkage of Virulence Genes in a Selfing Population of a Pakistani Dominant Race of Puccinia striiformis f. sp. tritici.
Wheat stripe rust is a severe threat of almost all wheat-growing regions in the world. Being an obligate biotrophic fungus, Puccinia striiformis f. sp. tritici (PST) produces new virulent races that break the resistance of wheat varieties. In this study, 115 progeny isolates were generated through sexual reproduction on susceptible Himalayan Berberis pseudumbellata using a dominant Pakistani race (574232) of PST. The parental isolate and progeny isolates were characterized using 24 wheat Yr single-gene lines and ten simple sequence repeat (SSR) markers. From the one-hundred-and-fifteen progeny isolates, 25 virulence phenotypes (VPs) and 60 multilocus genotypes were identified. The parental and all progeny isolates were avirulent to Yr5, Yr10, Yr15, Yr24, Yr32, Yr32, YrSp, YrTr1, YrExp2, Yr26, and YrTye and virulent to Yr1, Yr2, Yr6, Yr7, Yr8, Yr9, Yr17, Yr25, Yr27, Yr28, YrA, Yr44, and Yr3. Based on the avirulence/virulence phenotypes, we found that VPs virulent to Yr1, Yr2, Yr9, Yr17, Yr47, and YrA were controlled by one dominant gene; those to YrSp, YrTr1, and Yr10 by two dominant genes; and those to YrExp2 by two complementary dominant genes. The results are useful in breeding stripe rust-resistant wheat varieties and understanding virulence diversity.


Changes in the distribution of intermediate-filament types in Japanese quail embryos during morphogenesis.
We examined the distribution of intermediate filaments in early quail embryos in order to determine whether these cytoskeletal proteins play a role in the epithelial-mesenchymal transitions that commonly occur during embryogenesis, e.g., the separation of neural-crest cells from the neural epithelium. The distribution of cytokeratins, vimentin, and desmin was examined in frozen sections of quail embryos at stages during which dramatic reorganizations of tissues take place. All embryonic tissues were found to contain either vimentin or cytokeratins, but the distribution of these cytoskeletal proteins was characteristic neither of the cellular organization (e.g., epithelium vs. mesenchyme) nor of the germ-layer derivation of the tissues. Cytokeratin monoclonal antibodies stained most embryonic epithelia (defined here as being sheet-like tissue with an underlying basement membrane), including epidermis and extraembryonic membranes derived in part from the ectoderm, splanchnopleure and kidney tubules derived from mesoderm, and endoderm. Cytokeratin antibodies did not stain some epithelia, including the neural tube, neural plate, and dermatome/myotome. Whereas the cytokeratin antibodies exclusively stained epithelia, the vimentin antibodies labeled both epithelial (the neural tube, dermatome/myotome, and somatic and splanchnic mesoderm) and mesenchymal tissues (the sclerotome and neural-crest cells), regardless of their germ-layer derivation. In early embryos, antibodies against desmin only stained the myotome and, in 4-day embryos, the heart and mesenchyme around the pharynx. As the distribution of intermediate-filament types did not reflect tissue organization or germ-layer derivation, we propose that the distribution of intermediate filaments in early avian embryos reflects the motile capacity of an embryonic cell and/or the presence of specialized cell junctions, i.e., desmosomes.


Macrophage colony stimulating factor down-regulates MCSF-receptor expression and entry of progenitors into the osteoclast lineage.
Macrophage colony-stimulating factor (MCSF), although necessary for entry of precursors into the early preosteoclast pathway, inhibits osteoclastogenesis at high doses. To clarify the relationship between MCSF and osteoclast formation, we investigated the effect of exogenous MCSF in murine bone marrow culture. Precursor proliferation and the expression of MCSF-receptor were examined after 4 days of culture in the presence or absence of accessory stromal cells. In both mixed marrow and destromalized cell cultures, exogenous MCSF dose-dependently decreased 125I-MCSF binding (by 65 +/- 5.0% at 3500 and 87 +/- 16.7% at-7000 U/ml, respectively) while enhancing mononuclear cell proliferation after 3 days of exposure (by 2.8- and 6.3-fold, respectively). These effects were maintained 24 h after removal of exogenous MCSF and, as such, likely represented an MCSF-induced change in MCSF receptor-bearing cells. Exposure to exogenous MCSF (3500 U/ml) days 2-4 dose-dependently inhibited tartrate resistant acid phosphatase positive multinuclear cell (TRAP+ MNC) formation counted at the end of day 7, by 64.3 +/- 4.1%. This inhibition of TRAP+ MNC formation was preceded by a 92 +/- 9% decrease in the expression of carbonic anhydrase II mRNA measurable at 4 days. These results indicate that MCSF promotes proliferation of a population of cells expressing lower cognate receptor sites. Changes in MCSF-receptor expression appear to modulate the final lineage selection of the pluripotent monoblastic progenitor.


Stereotactic radiosurgery and the risk of haemorrhage from cavernous malformations.
Eighteen patients with cerebral cavernous malformations were treated with single dose of cobalt 60 source stereotactic radiosurgery. All had suffered at least one haemorrhage prior to treatment with six suffering 2, four suffering 3 and one suffering 4. Mean follow-up was 4.5 years. A total of 36 pretreatment haemorrhages occurred in 139 patient years. The first haemorrhage each patient suffered was taken as the start of observation and not included in the rehaemorrhage rate calculation. Three posttreatment haemorrhages occurred in 81 patient years of observation. The annual haemorrhage rate thus fell from 13% before to 3.7% after treatment. The odds ratio was thus 0.29 with a 95% confidence interval of (0.08-0.97), but this must be interpreted with caution because of the prereferral selection of this group of patients. Three patients developed complications of radiosurgery, two of them recovered fully.


Genetic Structure and Relationships among Wild and Cultivated Grapevines from Central Europe and Part of the Western Balkan Peninsula.
The genetic diversity and relationship between wild (Vitis vinifera L. subsp. sylvestris (Gmel.) Hegi and cultivated (V. vinifera L. subsp. vinifera) grapevine in the western Balkan region and Central Europe have not been studied together previously, although this area has a rich viticultural past. Here, we studied wild grapevine populations sampled from their natural habitats in several countries of the western Balkan region and Central Europe. Their genetic diversity and structure were compared to cultivars that are traditionally in use in this region. A sample set of 243 accessions was genotyped at 20 nuclear microsatellite loci, including 167 sylvestris and 76 diverse vinifera cultivars. The genetic diversity of the wild grapevines was lower than that of cultivars by all genetic parameters. Both hierarchical and nonhierarchical clustering methods differentiated two main groups, indicating clear separation between wild and cultivated vines but also revealed clear gene flow between the cultivated and wild gene pools through overlaps and admixed ancestry values in the graphs. There was greater affinity to the wild grapes in Central European cultivars than in Balkan cultivars. Fine arrangement of the structure among cultivated grapevines showed differentiation among Central European and Balkan cultivars. These results confirm the divergence of wild grapes from vinifera and highlight the "crossroad" role of the western Balkan peninsula in the broader context of European viticulture.


Chemical and stable isotopic characteristics of PM2.5 emitted from Chinese cooking.
This study investigated the characteristics of air pollutants generated from preparing Chinese cuisine and analyzed the isotopic compositions of carbon and nitrogen in particulate matter with a diameter <2.5 μm (PM2.5) to source apportionment study. The CO and CO2 concentrations and temperatures were measured using suitable instruments in real time during cooking, including stir-fry, fry, deep-fry, hot-pot, and mixed cooking, and periods with non-cooking. Personal environmental monitoring instruments were used to collect PM2.5 for carbon and nitrogen elements and isotopes analysis. Our data indicated that the concentrations of CO and CO2 and the temperature were higher during periods of cooking, especially for the fry and stir-fry methods, than during periods with non-cooking. The concentrations of PM2.5, total carbon, and total nitrogen were also higher during cooking; the maximum concentrations were measured during fry. The values of δ13C were considerably lower during the periods of cooking (mean: -28.15‰) than during non-cooking (-27.18‰). The average values of δ15N were 8.63‰ and 11.74‰ during deep-fry and hot-pot cooking, respectively. The δ13C values can be used to distinguish between cooking and other non-cooking sources and further assess the effect of different cooking activities on PM2.5. The δ15N only can be used to investigate the effect of deep-fry on PM2.5. Moreover, the δ13C signature suggested that fry emits higher products of incomplete combustion than do other cooking activities. These findings can assist in pollution source identification of PM2.5, emission control, and the study of combustion characteristics.


[Reoperation for refractory postoperative chylous ascites: value of peritoneovenous shunt combined with closure of lympho-peritoneal fistula].
Postoperative chylous ascites is a rare but serious complication resulting in denutrition, lymphopenia and infection. The first-intent treatment is usually conservative. We report a case of chylous ascites after retroperitoneal lymphadenectomy for testicular cancer, persisting despite conservative treatment then successfully treated by lymphostasis combined with peritoneovenous shunt. In case of high-output postoperative chylous ascites in low-risk patients with presumed localization of fistula, reoperation is indicated for lymphostasis. We advise to associate a peritoneovenous shunt in case of incomplete closure of the lymphoperitoneal fistula to avoid the morbidity of prolonged ascites.


Off-target function of the Sonic hedgehog inhibitor cyclopamine in mediating apoptosis via nitric oxide-dependent neutral sphingomyelinase 2/ceramide induction.
Sonic hedgehog (SHh) signaling is important in the pathogenesis of various human cancers, such as medulloblastomas, and it has been identified as a valid target for anticancer therapeutics. The SHh inhibitor cyclopamine induces apoptosis. The bioactive sphingolipid ceramide mediates cell death in response to various chemotherapeutic agents; however, ceramide's roles/mechanisms in cyclopamine-induced apoptosis are unknown. Here, we report that cyclopamine mediates ceramide generation selectively via induction of neutral sphingomyelin phosphodiesterase 3, SMPD3 (nSMase2) in Daoy human medulloblastoma cells. Importantly, short interfering RNA-mediated knockdown of nSMase2 prevented cyclopamine-induced ceramide generation and protected Daoy cells from drug-induced apoptosis. Accordingly, ectopic wild-type N-SMase2 caused cell death, compared with controls, which express the catalytically inactive N-SMase2 mutant. Interestingly, knockdown of smoothened (Smo), a target protein for cyclopamine, or Gli1, a downstream signaling transcription factor of Smo, did not affect nSMase2. Mechanistically, our data showed that cyclopamine induced nSMase2 and cell death selectively via increased nitric oxide (NO) generation by neuronal-nitric oxide synthase (n-NOS) induction, in Daoy medulloblastoma, and multiple other human cancer cell lines. Knockdown of n-NOS prevented nSMase2 induction and cell death in response to cyclopamine. Accordingly, N-SMase2 activity-deficient skin fibroblasts isolated from homozygous fro/fro (fragilitas ossium) mice exhibited resistance to NO-induced cell death. Thus, our data suggest a novel off-target function of cyclopamine in inducing apoptosis, at least in part, by n-NOS/NO-dependent induction of N-SMase2/ceramide axis, independent of Smo/Gli inhibition.


Keeping close: mothering with serious mental illness.
The aim of this paper is to describe the experiences of mothers with serious mental illness from their perspectives and how they attempted to manage their mothering circumstances. The desire to mother in women with serious mental illness is increasingly acknowledged by healthcare professionals. For these women, mothering is often framed as a pathological problem needing professional intervention. Yet little is known about mothering and illness from the perspectives of the mothers themselves. Using Glaser's grounded theory approach and both purposive and theoretical sampling, interviews were conducted with 20 mothers who were receiving treatment for mental health problems. The data were collected in 2002. We found the core category of Keeping close described mothers' efforts to have meaningful relationships with their children in the context of illness and suffering. To this end, mothers chose strategies that would hide illness for the sake of protecting their roles and their children. These strategies--masking, censoring speech, doing motherwork and seeking help--served to imitate ideal perceptions of mothering while making illness invisible to their children. Mothering in illness, however, became a vortex of contradictions, resulting in mothers 'hitting bottom', a point in time when they realized they could not keep close via pretences. To return to the valued place of mother, they sought treatment, hoping to learn how to be with their children authentically. To assist mothers with serious mental illness, healthcare professionals must be sensitive to the social and cultural context in which they mother in order to create healthier possibilities for nurturing their children.


Use of light traps and differing light color to investigate seasonal abundance of the date palm pest, Oryctes agamemnon arabicus (Coleoptera: Scarabaeidae).
Oryctes agamemnon arabicus (Fairmaire) (Coleoptera: Scarabaeidae) is a date palm insect pest that causes damage to trunk and roots and can damage grass lawns in the United Arab Emirates (UAE) and other countries such as Oman, Saudi Arabia, and Tunisia. The goal of this study was to monitor population dynamics and to evaluate six light colors (white, green, red, yellow, blue, and infrared) and two lamp types (mercury and energy-saving) in light traps. Experiments were performed on a date palm farm during a 2 yr period (2010 and 2011). It was found that this insect is a univoltine pest with a single population peak. Adults appeared in the field around middle of April and early May and the population continued to build until maximum numbers were reached in mid June. No adults were found after the end of September. Photoperiod showed a significant correlation with the changes in adult population size. White light emitted from mercury lamps attracted significantly more O. agamemnon arabicus adults compared with the other tested light colors. Increasing the wattage of mercury lamps from 160 to 250 watt did not significantly increase the number of collected insects. The results demonstrated that light traps equipped with 160-watt mercury lamps emitting white light collected significantly the highest number of this insect among the other tested lamps.


Statistical stopping criteria for automated screening in systematic reviews.
Active learning for systematic review screening promises to reduce the human effort required to identify relevant documents for a systematic review. Machines and humans work together, with humans providing training data, and the machine optimising the documents that the humans screen. This enables the identification of all relevant documents after viewing only a fraction of the total documents. However, current approaches lack robust stopping criteria, so that reviewers do not know when they have seen all or a certain proportion of relevant documents. This means that such systems are hard to implement in live reviews. This paper introduces a workflow with flexible statistical stopping criteria, which offer real work reductions on the basis of rejecting a hypothesis of having missed a given recall target with a given level of confidence. The stopping criteria are shown on test datasets to achieve a reliable level of recall, while still providing work reductions of on average 17%. Other methods proposed previously are shown to provide inconsistent recall and work reductions across datasets.


Parsimonious and efficient assessment of health-related quality of life in osteoarthritis research: validation of the Assessment of Quality of Life (AQoL) instrument.
The Assessment of Quality of Life (AQoL) utility instrument was psychometrically developed for the general population. This study aimed to explore its potential as an osteoarthritis (OA) outcome measure. WOMAC, Lequesne index, SF-36, Visual analogue scales and the AQoL were administered to 222 people with OA. The ability of each questionnaire to detect differences between groups was based on (i) self-rated health (SRH) and, (ii) differences between people on an orthopedic waiting list (WL) vs people with OA in the community (C). Comparisons included effect size, relative efficiency and receiver operator characteristic curves. All instruments detected differences between groups; however no one instrument exhibited superior efficiency. The AQoL demonstrated strong psychometric properties. The AQoL has equivalent performance to comparator questionnaires commonly used in OA research and would be a useful adjunct to well-established disease specific scales. The AQoL has important advantages; brevity (12 items), facilitates comparisons between disease groups, and delivers a utility score that can be used in health economic evaluations.


A low latency and low power indirect topology for on-chip communication.
This paper presents the Hybrid Scalable-Minimized-Butterfly-Fat-Tree (H-SMBFT) topology for on-chip communication. Main aspects of this work are the description of the architectural design and the characteristics as well as a comparative analysis against two established indirect topologies namely Butterfly-Fat-Tree (BFT) and Scalable-Minimized-Butterfly-Fat-Tree (SMBFT). Simulation results demonstrate that the proposed topology outperforms its predecessors in terms of performance, area and power dissipation. Specifically, it improves the link interconnectivity between routing levels, such that the number of required links isreduced. This results into reduced router complexity and shortened routing paths between any pair of communicating nodes in the network. Moreover, simulation results under synthetic as well as real-world embedded applications workloads reveal that H-SMBFT can reduce the average latency by up-to35.63% and 17.36% compared to BFT and SMBFT, respectively. In addition, the power dissipation of the network can be reduced by up-to33.82% and 19.45%, while energy consumption can be improved byup-to32.91% and 16.83% compared to BFT and SMBFT, respectively.


Neural networks for blind-source separation of Stromboli explosion quakes.
Independent component analysis (ICA) is used to analyze the seismic signals produced by explosions of the Stromboli volcano. It has been experimentally proved that it is possible to extract the most significant components from seismometer recorders. In particular, the signal, eventually thought as generated by the source, is corresponding to the higher power spectrum, isolated by our analysis. Furthermore, the amplitude of the source signals has been found by using a simple trick and so overcoming, for this specific case, the classical problem of ICA regarding the amplitude loss of the separated signals.


Dysregulation of peritoneal cavity B1a cells and murine primary biliary cholangitis.
Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease with progressive cholestasis and liver fibrosis. Similar to human patients with PBC, p40-/-IL-2Rα-/- mice spontaneously develop severe autoimmune cholangitis. Although there has been considerable work on immune regulation and autoimmunity, there is a relative paucity of work directed at the functional implications of the key peritoneal cavity (PC) B cell subset, coined B1a cells in PBC. We used flow cytometry and high-resolution microarrays to study the qualitative and quantitative characteristics of B cells, particularly B1a cells, in the PC of p40-/-IL-2Rα-/- mice compared to controls. Importantly, B1a cell proliferation was markedly lower as the expression of Ki67 decreased. Meanwhile, the apoptosis level was much higher. These lead to a reduction of B1a cells in the PC of p40-/-IL-2Rα-/- mice compared to controls. In contrast, there was a dramatic increase of CD4+ and CD8+ T cells accompanied by elevated production of IFN-γ. In addition, we found a negative correlation between the frequency of B1a cells and the presence of autoreactive CD8+ T cells in both liver and PC of p40-/-IL-2Rα-/- mice. From a functional perspective, B cells from p40-/-IL-2Rα-/- mice downregulated IL-10 production and CTLA-4 expression, leading to loss of B cell regulatory function. We suggest that the dysfunction of B1a cells in the PC in this murine model of autoimmune cholangitis results in defective regulatory function. This highlights a new potential therapeutic target in PBC.


Looking for dangerous places: some aspects of medical geography and disease mapping.
Medical geography investigates spatial patterns in the distribution of disease occurrence. The origins of the field can be traced to antiquity, but mapping of disease did not appear until the mid-19th century. Maps can reveal distinctive spatial patterns of certain diseases and may suggest environmental correlates. The geographical distribution of many infectious diseases, such as malaria, with well-known ecology are usually easily understood. The etiology of certain chronic non-infectious diseases which exhibit noticeable geographic variation is often complex. A map of cerebrovascular disease mortality rates in Appalachia is used as an example of an application of modern medical geography.


Use of alumina, sephadex G10, and ion-exchange columns to purify samples for determination of epinephrine, norepinephrine, dopamine, homovanillic acid, and 5-hydroxyindoleacetic acid in urine.
We investigated the usefulness of small Sephadex columns, prepared in Pasteur pipettes, in purifying samples to be analyzed for catecholamines, homovanillic acid, and 5-hydroxyindoleacetic acid. After free catecholamines in urine samples were purified on alumina followed by Sephadex G10, a reliable and simultaneous quantification of epinephrine, norepinephrine, and dopamine was achieved by using high-performance liquid-chromatography with electrochemical detection. Purification of urine on Bio-Rad prepacked ion-exchange columns followed by Sephadex G10 resulted in a reliable, fast (200 samples processed per week) method for determination of free catecholamines in urine. Analytical recoveries of both methods were between 80 and 95%, with a CV of about 3%. Single purification on Sephadex G10 sufficed to allow simultaneous determination of homovanillic acid and 5-hydroxyindoleacetic acid in urine. Analytical recovery for this method was about 90%, with a CV of about 5%. Sephadex G10 columns, which can be re-used without regeneration for at least one year, appear to have a great potential in clinical chemistry.


Comparison of mouse and rat cytochrome P450-mediated metabolism in liver and intestine.
The liver is considered to be the major site of first-pass metabolism, but the small intestine is also able to contribute significantly. The improvement of existing in vitro techniques and the development of new ones, such as intestinal slices, allow a better understanding of the intestine as a metabolic organ. In this paper, the formation of metabolites of several human CYP3A substrates by liver and intestinal slices from rat and mouse was compared. The results show that liver slices exhibited a higher metabolic rate for the majority of the studied substrates, but some metabolites were produced at a higher rate by intestinal slices, compared with liver slices. Coincubation with ketoconazole inhibited the metabolic conversion in intestinal slices almost completely, but inhibition was variable in liver slices. To better understand the role of CYP3A in mice, we studied the relative mRNA expression of different CYP3A isoforms in intestine and liver from mice because, in this species, CYP3A expression has not been well described in these organs. It was found that in mice, CYP3A13 is more expressed in the intestine, whereas CYP3A11, CYP3A25, and CYP3A41 are more expressed in the liver, comparable to similar findings in the rat. Altogether, these data demonstrate that, in addition to liver, the intestine from mouse and rat may have an important role in the process of first-pass metabolism, depending on the substrate. Moreover, we show that intestinal slices are a useful in vitro technique to study gut metabolism.


X-ray atomic orbital analysis. I. Quantum-mechanical and crystallographic framework of the method.
The scattering unit of X-ray crystal structure analysis is changed from atoms to the subshell electrons by X-ray atomic orbital analysis (XAO). All the atoms in the unit cell are divided into groups of subshell electrons in the XAO analysis. Each subshell is treated as an independent pseudo-atom, which enables the atomic orbitals (AO's) and the electron population of each AO expressed as a linear combination of s/p/d/f orbitals in each subshell to be determined. When the environmental condition of the sample is varied, the electron transfer among the AO's in the crystal can be traced with XAO. It is applicable mainly to analyses of the electron-density distribution in ionic solids including those with a nonstoichiometric structure. The expansion coefficients of each AO are calculated with the perturbation theory putting a point charge on each atom in the unit cell. This automatically makes the perturbation potential have the point-group symmetry of the atom in the crystal field. Then the coefficients of each AO are refined to fit to the observed structure factors keeping the orthonormal relationships among the AO's. Complex basis functions with alpha or beta spin as well as real ones are employed for heavy atoms and the relationships among the coefficients for the AO's of an electron in the crystal fields of the 32 point-group symmetries are derived for p, d and f orbitals. The AO's thus derived can be applicable to an anti-symmetrized multi-electron system, although X-ray diffraction cannot specify the atomic terms occupied when the crystal symmetry permits the atom to have many terms.


Mutations in the Parkinson's disease genes, Leucine Rich Repeat Kinase 2 (LRRK2) and Glucocerebrosidase (GBA), are not associated with essential tremor.
We evaluated an association between essential tremor (ET) and the Parkinson's disease (PD) genes, Leucine Rich Repeat Kinase 2 (LRRK2) and Glucocerebrosidase (GBA). Clinical studies demonstrate an association between ET and PD, suggesting possible shared pathophysiologies, yet LRRK2 has rarely been studied in ET, and GBA, not at all. ET cases (n = 275, including 42 with rest tremor) and controls (n = 289) were enrolled in an epidemiological study (Columbia University). Post-mortem brain tissue samples were obtained on 24 additional ET cases, including 3 with brainstem Lewy bodies. We performed a comprehensive analysis of the LRRK2 gene by genotyping 4 LRRK2 mutations (G2019S, I2020T, R1441C and Y1699C), 2 rare LRRK2 variants (L1114L and I1122V) and 19 LRRK2 SNPs. All GBA exons were sequenced in a subset of 93 Ashkenazi Jewish (AJ) cases, 62 AJ controls and 24 ET brains. LRRK2 mutations were not found in any ET cases or ET brains and none of the LRRK2 SNPs was associated with ET. GBA mutations were found in 7.5% (7/93) of AJ ET cases and 4.8% (3/62) of AJ controls (p = 0.75). 8.3% (2/24) of ET brains carried a GBA mutation. Four different heterozygous mutations were identified, including 3 previously reported mutations (N370S, R496H, and E326K) and 1 new missense variant (R44C). As suggested by several smaller prior reports, the known mutations for the LRRK2 gene are not risk factors for ET. Furthermore, a similar frequency of GBA mutations in AJ ET cases and controls suggests that GBA is not a common cause of ET either.


Quantitative contribution of NHE2 and NHE3 to rabbit ileal brush-border Na+/H+ exchange.
Intestinal neutral NaCl absorption, which is made up of brush-border (BB) Na+/H+ exchange linked to BB Cl-/HCO3- exchange, is up- and downregulated as part of digestion and diarrheal diseases. Glucocorticoids stimulate ileal NaCl absorption and BB Na+/H+ exchange. Intestinal BB contains two Na+/H+ exchanger isoforms, NHE2 and NHE3, but their relative roles in rabbit ileal BB Na+/H+ exchange has not been determined. A technique to separate the contribution of NHE2 and NHE3 to ileal BB Na+/H+ exchange activity was standardized by using an amiloride-related compound, HOE-694. Under basal conditions, both NHE2 and NHE3 contribute approximately 50% to ileal Na+/H+ exchange. Glucocorticoids (methylprednisolone) increase BB Na+/H+ exchange (2.5 times) but increase only ileal NHE3 activity (4.1 times), without an effect on NHE2 activity. Thus ileal BB Na+/H+ exchange in animals treated with glucocorticoids is 69% via NHE3. A quantitative Western analysis for NHE3 was developed, using as an internal standard a fusion protein of the COOH-terminal 85 amino acids of NHE3 and maltose binding protein. Glucocorticoid treatment increased the amount of BB NHE3. The quantitative Western analysis showed that NHE3 makes up 0.018% of ileal BB protein in control rabbits and 0.042% (2.3 times as much) in methylprednisolone-treated rabbits. Methylprednisolone treatment did not alter the amount of ileal BB NHE2 protein. NHE3 turnover number was estimated to be 458 cycles/s under basal conditions and 708 cycles/s in glucocorticoid-treated ileum. Thus methylprednisolone stimulates ileal BB Na+/H+ exchange activity only by an effect on NHE3 and not on NHE2; it does so primarily by increasing the amount of BB NHE3, although it also increases the NHE3 turnover number.


Comparative calibration without a gold standard.
Comparative calibration is the broad statistical methodology used to assess the calibration of a set of p instruments, each designed to measure the same characteristic, on a common group of individuals. Different from the usual calibration problem, the true underlying quantity measured is unobservable. Many authors have shown that this problem, in general, does not have a unique solution. Most commonly used assumptions to obtain a unique solution are (i) one instrument is the gold standard (that is, unbiased) and (ii) the measurement errors of the p instruments are independent. Such constraints, however, may not be valid for many clinical applications, for example, the universal standardization project for dual X-ray absorptiometry (DXA) scanners. In this paper, we propose a new approach to resolve the comparative calibration problem when a gold standard is unavailable. Instead of the usual assumptions, we use external information in addition to data from the p instruments, to solve the problem. We address statistical estimation, hypothesis testing and missing data problems. We apply the new method specifically to the universal standardization project data where a group of individuals have been measured for bone mineral density (BMD) by three DXA scanners. We compare the results of the new method to currently used methods and show that they have better statistical properties.


[Serology of cutaneous sporotrichosis].
Sporothrix schenckii antigens were tested with seventy-nine sera from human cases of sporotrichosis for their value in the serological diagnosis of extracutaneous forms of the disease. 55.7% of the sera reacted in the tube agglutination test; 29.1% of them were positive by counter immunoelectrophoresis and only 7.6% reacted in the simple immunodiffusion test. There was a clear correlation between agglutination titers and the respective reactivity of sera by counter immunoelectrophoresis. By immunoelectrophoresis, 2 different anodic precipitin bands were observed between S. schenckii metabolic antigen and anti-Sporothrix hyperimmune animal sera. Since no false positive reactions were found in sera from patients with other mycoses, and considering the simplicity of the antigen preparation, we agree with previous authors that these methods may be useful for the detection of visceral forms of sporotrichosis.


[Pattern of survival and sequelae in very low birth weight infants].
The survival and sequelae of the very low birth weight (VLBW) newborns are reported. Two time-periods have been compared (1980-84 vs 1985-88) as well as two weight groups. (Lower than 1,000 vs 1,000-1,499). A total number of 205 VLBW were admitted, and 74 died. Only 72 were used to study morbidity and sequelae with a minimum follow-up of 12 months after correcting age. Those with a weight lower than 1,000 g have a greater motor impairment, (45.5 vs 16.4%), cognitive deficiency (55.5 vs 14.8%), myopia (27.3 vs 3.3%), neurosensorial deafness (27.3 vs 0%), and overall sequelae. During the period 1985-88, survival was 77.9% of the VLBW have any sequelae (12.5% major sequelae and 15.3% minor sequelae). A 36.4% of the newborns with a weight under 1,000 g have major sequelae comparing with the 8.2% in the others. Growth delay is closely related to neurologic sequelae.


Emerging Alternative Proteinases in APP Metabolism and Alzheimer's Disease Pathogenesis: A Focus on MT1-MMP and MT5-MMP.
Processing of amyloid beta precursor protein (APP) into amyloid-beta peptide (Aβ) by β-secretase and γ-secretase complex is at the heart of the pathogenesis of Alzheimer's disease (AD). Targeting this proteolytic pathway effectively reduces/prevents pathology and cognitive decline in preclinical experimental models of the disease, but therapeutic strategies based on secretase activity modifying drugs have so far failed in clinical trials. Although this may raise some doubts on the relevance of β- and γ-secretases as targets, new APP-cleaving enzymes, including meprin-β, legumain (δ-secretase), rhomboid-like protein-4 (RHBDL4), caspases and membrane-type matrix metalloproteinases (MT-MMPs/η-secretases) have confirmed that APP processing remains a solid mechanism in AD pathophysiology. This review will discuss recent findings on the roles of all these proteinases in the nervous system, and in particular on the roles of MT-MMPs, which are at the crossroads of pathological events involving not only amyloidogenesis, but also inflammation and synaptic dysfunctions. Assessing the potential of these emerging proteinases in the Alzheimer's field opens up new research prospects to improve our knowledge of fundamental mechanisms of the disease and help us establish new therapeutic strategies.


Piezoelectric technology for pediatric autologous cranioplasty.
Objective : Pediatric patients with skull defects larger than available sources for splitting bicortical bone have limited options for autogenous cortical bone cranioplasty. Piezoelectric instruments allow donor bone to be chosen based on the best possible contour rather than the presence of bicortical bone. We present the use of piezoelectric technology to split thin unicortical calvarium for autogenous cranioplasty in a series of pediatric patients. Design : Retrospective review of a series of pediatric patients requiring reconstruction for skull defects. Patients/Intervention : Our series included a 2-year-old with a parietal skull tumor and resultant 3 × 3-cm defect after craniectomy, a 2-year-old with a 3 × 3-cm defect after excision of an occipital skull tumor, a 10-year-old with a 4 × 5-cm skull defect after excision of an occipital skull tumor, and a 13-year-old who suffered a gunshot to the forehead with a 12 × 7-cm frontal skull defect. We used a piezoelectric saw to precisely and safely split unicortical and bicortical cranium that ranged from 1 to 3 mm in thickness. The inner layer was used to reconstruct the donor site; whereas, the outer layer was used for the craniectomy defect. Conclusion : The piezoelectric saw allows unicortical bone to be split and used for cortical bone cranioplasty. This technology allows choice of donor site based on the best contour rather than the presence of bicortical bone. This technique expands the possibilities of autogenous cranioplasty and enables primary repair of cranial defects that would otherwise require secondary cranioplasty with remote donor sites, foreign materials, or unstable particulate cranioplasty.


Comparison of kinetic properties between plant and fungal amine oxidases.
Kinetic properties of novel amine oxidases isolated from a mold Aspergillus niger AKU 3302 were compared to those of typical plant amine oxidase from pea seedling (EC 18.104.22.168). Pea amine oxidase showed highest affinity with diamines, such as putrescine and cadaverine, while fungal enzymes oxidized preferably n-hexylamine and tyramine. All enzymes were inhibited by carbonyl reagents, copper chelating agents, some substrate analogs and alkaloids, but there were quite significant differences in the sensitivity and inhibition modes. Aminoguanidine, which strongly inhibited pea amine oxidases showed only little effect on fungal enzymes. Substrate analogs such as 1.5-diamino-3-pentanone and 1-amino-3-phenyl-3-propanone, which were potent competitive inhibitors of pea amine oxidases, inhibited fungal enzymes much more weakly and non competitively. Also various alkaloids behaving as competitive inhibitors of pea amine oxidase inhibited the fungal enzymes non competitively. Very surprising was the potent inhibition of fungal enzymes by artificial substrates of pea amine oxidases, E- and Z-1,4-diamino-2-butene. The relationships between the different inhibition modes and possible binding at the active site are discussed.


Graduate follow-up in the University of Wisconsin family practice residency programs.
Between June 30, 1973, and June 30, 1980, 100 family physicians completed their family practice residency training at the University of Wisconsin Medical School. Ninety-seven graduates completed an extensive 13-page mail survey. The primary purposes of the study were to measure the adequacy of the graduate's residency training program and to determine how well the graduates have done as family physicians. A majority of respondents considered themselves adequately prepared in most areas listed with a few noticeable exceptions. For example, 50 percent or more felt underprepared in fracture care, emergency surgery, and applying forceps for vaginal deliveries. For selected administrative and financial aspects of a practice, more than 60 percent felt underprepared. In general, the graduates were satisfied with the potential for practice growth as well as their current level of income. Regarding hospital privileges, between 85 and 93 percent of the graduates were very satisfied with the availability and extent of their privileges. Finally, all 100 graduates are board certified in family practice and at this writing none have changed into another specialty or intend to do so in the foreseeable future.


Proteomic responses to metal-induced oxidative stress in hydrothermal vent-living mussels, Bathymodiolus sp., on the Southwest Indian Ridge.
Bathymodiolin mussels are amongst the dominant fauna occupying hydrothermal vent ecosystems throughout the World's oceans. This subfamily inhabits a highly ephemeral and variable environment, where exceptionally high concentrations of reduced sulphur species and heavy metals necessitate adaptation of specialised detoxification mechanisms. Whilst cellular responses to common anthropogenic pollutants are well-studied in shallow-water species, they remain limited in deep-sea vent fauna. Bathymodiolus sp. were sampled from two newly-discovered vent sites on the Southwest Indian Ridge (Tiamat and Knuckers Gaff) by the remotely operated vehicle (ROV) Kiel 6000 during the RRS James Cook cruise, JC 067 in November 2011. Here, we use redox proteomics to investigate the effects of tissue metal accumulation on protein expression and thiol oxidation in gill. Following 2D PAGE, we demonstrate a significant difference in intensity in 30 protein spots in this organ between the two vent sites out of 205 matched spots. We also see significant variations in thiol oxidation in 15 spots, out of 143 matched. At Tiamat, 23 protein spots are up-regulated compared to Knuckers Gaff and we identify 5 of these with important roles in metabolism, cell structure, stress response, and redox homeostasis. We suggest that increased metal exposure triggers changes in the proteome, regulating tissue uptake. This is evident both between vent sites and across a chemical gradient within the Knuckers Gaff vent site. Our findings highlight the importance of proteomic plasticity in successful adaptation to the spatially and temporally fluctuating chemical environments that are characteristic of hydrothermal vent habitats.


Inducible expression of p21WAF-1/CIP-1/SDI-1 from a promoter conversion retroviral vector.
Constitutive, high-level expression of the potentially therapeutic WAF-1/CIP-1/SDI-1 gene is incompatible with cell growth. A promoter conversion retroviral vector carrying the WAF-1/CIP-1/SDI-1 gene under the transcriptional control of the glucocorticoid inducible promoter of mouse mammary tumor virus was used to infect human bladder carcinoma or feline kidney cells. Reduced cell growth due to a greater proportion of cells being in the G0/G1 phase of the cell cycle was observed when WAF-1/CIP-1/SDI-1 expression was activated by addition of glucocorticoid hormone. This system demonstrates the potential long-term therapeutic use of WAF-1/CIP-1/SDI-1 delivered by retroviral vectors for inhibiting the growth of rapidly proliferating cells. Moreover, the conditional expression of genes such as WAF-1/CIP-1/SDI-1 from such retroviral vectors may facilitate analysis of their function.


Intra- and interspecific variation in macaque molar enamel thickness.
Enamel thickness has played an important role in studies of primate taxonomy, phylogeny, and functional morphology, although its variation among hominins is poorly understood. Macaques parallel hominins in their widespread geographic distribution, relative range of body sizes, and radiation during the last five million years. To explore enamel thickness variation, we quantified average and relative enamel thickness (AET and RET) in Macaca arctoides, Macaca fascicularis, Macaca fuscata, Macaca mulatta, Macaca nemestrina, and Macaca sylvanus. Enamel area, dentine area, and enamel-dentine junction length were measured from mesial sections of 386 molars scanned with micro-computed tomography, yielding AET and RET indices. Intraspecific sex differences were not found in AET or RET. Macaca fuscata had the highest AET and RET, M. fascicularis showed the lowest AET, and M. arctoides had the lowest RET. The latitudinal distribution of macaque species was associated with AET for these six species. Temperate macaques had thicker molar enamel than did tropical macaques, suggesting that thick enamel may be adaptive in seasonal environments. Additional research is needed to determine if thick enamel in temperate macaques is a response to intensified hard-object feeding, increased abrasion, and/or a broader diet with a greater range of food material properties. The extreme ecological flexibility of macaques may prohibit identification of consistent trends between specific diets and enamel thickness conditions. Such complications of interpretation of ecological variability, dietary diversity, and enamel thickness may similarly apply for fossil Homo species.


Consumer sensory evaluation, fatty acid composition, and shelf-life of ground beef with subcutaneous fat trimmings from different carcass locations.
Brisket, chuck, plate, flank, and round subcutaneous fat trim were used to produce ground beef patties then evaluated for color, lipid oxidation, fatty acid composition, volatile chemical compounds and consumer sensory evaluation. Color, TBARS, consumer sensory evaluation, and cook/freezer loss did not differ (P>0.05) among carcass fat locations. Percentage stearic acid was lower (P=0.044) in the ground beef using brisket fat than using the chuck and flank fat. Patties made with brisket fat were higher in cis-vaccenic acid (P=0.016) and the saturated to monounsaturated fatty acid ratio (P=0.018) than all other sources of subcutaneous fat. Butanedione was highest (P=0.013) in patties using flank and plate fat. Ground beef with brisket fat was higher (P=0.003) than all other sources for beefy aroma. Altering the profile of non-polar, triglyceride fatty acids has no effect on sensory flavor or major volatile chemical compounds.